Diabetes mellitus type 2 medical therapy

	Diabetes mellitus main page
	Diabetes mellitus type 2 Microchapters
Home
Patient information
Overview
Historical Perspective
Pathophysiology
Causes
Differentiating Diabetes Mellitus Type 2 from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
Chest X Ray
CT
MRI
Echocardiography or Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical therapy Life Style Modification Pharmacotherapy Glycemic Control
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]Anahita Deylamsalehi, M.D.[3]Javaria Anwer M.D.[4]Basir Gill, M.B.B.S, M.D.[5]

Overview

The main goals of treatment are to eliminate hyperglycemic symptoms, control the long term complications and improve the patient's quality of life. Diabetes mellitus type 2 is initially treated by life style modification and weight loss, especially in obese patients. Metformin is the first line pharmacologic therapy that is usually started once the diagnosis is confirmed unless contraindications exist. Nevertheless, in patients presented with high HbA1C/fasting blood sugar levels or if glycemic goals are not achieved, a second agent must be added to metformin. A wide range of options are available to add as combination therapy based on the patient's condition and comorbidities.

Pharmacologic therapy

Inpatients

Outpatients

A network meta-analysis summarizes the risks and benefits of available medications for diabetes mellitus type 2^[1].

Medical therapy starts with metformin monotherapy unless there is a contraindication for it. In the following conditions, treatment starts with dual therapy:^[2]^[3]^[4]^[5]^[6]^[7]
- If HbA1C is greater than 9, start with dual oral blood glucose lowering agent.
- If HbA1C is greater than 10 or blood glucose is more than 300 mg/dl or patient is markedly symptomatic, consider combination therapy with insulin.

The most effective class of drugs for reducing death are probably sodium glucose transporter 2 (SGLT2) inhibitors or GLP-1 receptor agonists.^[8]

Metformin

Metformin is effective, safe and inexpensive.
It may reduce risk of cardiovascular events and death.
Patients should be advised to stop the medication in cases of nausea, vomiting or dehydration.
Metformin is capable of decreasing the body weight but it's effect on muscle mass is unclear.^[9]
A systemic review, observing 34,000 patients in total concluded that Metformin is as safe as other anti-diabetic treatments in diabetic patients with heart failure.^[10]
Some studies demonstrated lower risk of mortality in diabetic patients with concurrent COPD or Asthma who were taking Metformin compared to non-users.^[11]
Metformin use in diabetic patients with sepsis, tuberculosis and Chronic obstructive pulmonary disease (COPD) were associated with lower mortality rate.^[12]^[13]
One of the possible effects of Metformin is gut microbiota alteration, which results in Tauroursodeoxycholic acid (TUDCA) and Glycoursodeoxycholic Acid (GUDCA) elevation. Since both TUDCA and GUDCA act as intestinal farnesoid X receptor (FXR) antagonists, they can be effective in hyperglycemia treatment.^[14]

Contraindications

As of June 2020, The US Food and Drug Administration (FDA) recalls extended-release metformin which is made by few pharma companies due to detection of high levels of N-Nitrosodimethylamine (NDMA).^[15]^[16]
N-Nitrosodimethylamine (NDMA) is a carcinogenic agent when exposed in higher levels leads to cancer.
The following are the pharma companies that the FDA recalls the extended-release metformin:
- Lupin
- Apotex Corp
- Actavis
- Time-Cap Labs, Inc
- Amneal
Contraindications to metformin include, heart failure, liver failure, GFR ≤30 and metabolic acidosis.

,Randomized controlled trial comparing initial doses for metformin^[17].
Total duration was 14 weeks with at least 8 weeks on final dose.	Placebo	500 mg once daily	1000 mg (500 mg twice daily)	1500 mg (500 mg thrice daily)	2000 mg (1000 mg twice daily)	2500 mg (1000 am, 500 lunch, 1000 at supper daily
Any GI ADR	13%	16%	29%	24%	23%	29%
Diarrhea	5%	8%	21%	12%	19%	14%
HbA1c change	+ 1.2	+ 0.3	+ 0.1	- 0.5	- 0.8	- 0.04
Source: Garber AJ, Duncan TG, Goodman AM, Mills DJ, Rohlf JL (1997). "Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose-response trial". Am J Med. 103 (6): 491–7. doi:10.1016/s0002-9343(97)00254-4. PMID 9428832.

Insulin

The lack of inexpensive, generic insulin may lead to underuse of insulin^[18] and occurs for unusual reasons^[19].
The insulin analogues may not provide a meaningful advantage^[20]^[21]^[22].
Although Insulin increases the body weight, some data suggest that it is capable of increasing the muscle mass.^[23]
A meta-analysis of randomized controlled trials by the Cochrane Collaboration found "only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2" compared to human insulin^[22] More recent randomized controlled trials have found no differences with glargine^[24] and have found that although long acting insulins were less effective, they were associated with less hypoglycemia.^[25]
Premixed combinations of insulin, human or analogue, have similar reductions in HbA1c^[26]. A cohort study likewise found similar rates of hypoglycemia^[21].

Bedtime insulin

For Diabetes mellitus type 2:

Initially, a randomized controlled trial found that adding bedtime insulin to patients failed oral medications is more effective and with less weight gain than using multiple dose insulin.^[27] Nightly insulin combines better with metformin that with sulfonylureas.^[28]

More recently, the Cochrane Collaboration concluded: "hypoglycaemic events were rare and the absolute risk reducing effect was low. Approximately one in 100 people treated with insulin detemir instead of NPH insulin benefited. In the studies, low blood glucose and HbA1c targets, corresponding to near normal or even non-diabetic blood glucose levels, were set. Therefore, results from the studies are only applicable to people in whom such low blood glucose concentrations are targeted"^[29].

Kaiser Permanente, in a large cohort study, found no benefit from long-acting insulin analogues compared to human NPH insulin^[21].

Dosing

The initial dose of nightly insulin (measured in IU/d) should be equal to the fasting blood glucose level (measured in mmol/L)^[27]. If the fasting glucose is reported in mg/dl, multiple by 0.05551 (or divided by 18) to convert to mmol/L.^[30]

Consider increasing by 3 units at a time^[31].

Monitoring

In both trails above, dosing was adjusted by monitoring fasting sugars^[27]^[28]. In the second trial, the patient checked their "diurnal blood glucose level, measurements were taken before and 1.5 hours after breakfast, lunch and dinner; at 10 p.m.; and at 4 a.m." once a week for the first 3 months and then every other week^[28].

Availability

Novo Nordisk’s Novolin ReliOn N is less expensive at Walmart and CVS pharmacies^[32].

Combination therapy

Any agent can be added as second drug based on patient condition. Nevertheless, the American Association of Clinical Endocrinologists recommends either incretin based therapy or sodium glucose transporter 2 (SGLT2) inhibition agents.^[6]^[33]

The following table summarize the available FDA approved glucose lowering agents that may help to individualize treatment for each patient.

Class	Drug	Mechanism of action	Primary physiologic action	Advantages	Disadvantages	Cost
Biguanides	Metformin	Activates AMP-kinase	↓ Hepatic glucose production	Extensive experience Rare hypoglycemia ↓ CVD events Relatively higher A1C efficacy	Gastrointestinal side effects (diarrhea, abdominal cramping, nausea) Vitamin B12 deficiency Contraindications: eGFR ≤30 mL/min/1.73 m2, acidosis, hypoxia, dehydration. Lactic acidosis risk (rare)	Low
Sulfonylureas	2nd generation Glyburide Glipizide Glimepiride	Closes K-ATP channels on beta cell plasma membranes	↑ Insulin secretion	Extensive experience ↓ Microvascular risk Relatively higher A1C efficacy	Hypoglycemia ↑ Weight	Low
Meglitinides	Repaglinide Nateglinide	Closes K-ATP channels on beta cell plasma membranes	↑ Insulin secretion	↓ Postprandial glucose excursions Dosing flexibility	Hypoglycemia ↑ Weight Frequent dosing schedule	Moderate
Thiazolidinedione (TZDs)	Pioglitazone^‡ Rosiglitazone^§	Activates the nuclear transcription factor PPAR-gama	↑ Insulin sensitivity	Rare hypoglycemia Relatively higher A1C efficacy Durability ↓ Triglycerides (pioglitazone) ↓ CVD events (PROactive, pioglitazone) ↓ Risk of stroke and MI in patients without diabetes and with insulin resistance and history of recent stroke or TIA Pioglitazone use is associated with higher chance of pneumonia^[34]	↑ Weight Edema/heart failure Bone fractures ↑ LDL-C (rosiglitazone)	Low
α-Glucosidase inhibitors	Acarbose Miglitol	Inhibits intestinal α-glucosidase	Slows intestinal carbohydrate digestion/absorption	Rare hypoglycemia ↓ Postprandial glucose excursions ↓ CVD events in prediabetes Nonsystemic	Generally modest A1C efficacy Gastrointestinal side effects (flatulence, diarrhea) Frequent dosing schedule	Low to moderate
DPP-4 inhibitors	Sitagliptin Saxagliptin Linagliptin Alogliptin	Inhibits DPP-4 activity, increasing postprandial incretin (GLP-1, GIP) concentrations	↑ Insulin secretion (glucose dependent) ↓ Glucagon secretion (glucose dependent)	Rare hypoglycemia Well tolerated	Angioedema/urticaria and other immune-mediated dermatological effects Acute pancreatitis ↑ Heart failure hospitalizations (saxagliptin, alogliptin)	High
Bile acid sequestrants	Colesevelam	Binds bile acids in intestinal tract, increasing hepatic bile acid production	↓ Hepatic glucose production ↑ Incretin levels	Rare hypoglycemia ↓ LDL-C	Modest A1C efficacy Constipation ↑ Triglycerides May ↓ absorption of other medications	High
Dopamine-2 agonists	Bromocriptine (quick release)^§	Activates dopaminergic receptors	Modulates hypothalamic regulation of metabolism ↑ Insulin sensitivity	Rare hypoglycemia ↓ CVD events	Modest A1C efficacy Dizziness/syncope Nausea Fatigue Rhinitis	High
SGLT2 inhibitors	Canagliflozin Dapagliflozin^‡ Empagliflozin	Inhibits SGLT2 in the proximal nephron	Blocks glucose reabsorption by the kidney,increasing glucosuria	Rare hypoglycemia ↓ Weight ↓ Blood pressure ↓ The chance of kidney disease progression, including the macroalbuminuria. They are also capable of lowering the risk of worsening estimated glomerular filtration rate, end-stage kidney disease, or death due to renal failure.^[35] Research shows that SGLT-2 inhibitors and GLP-1 receptor agonists reduce cardiovascular and renal outcomes among patients with diabetes type 2.^[36] Empagliflozin is associated with lower CVD event rate and mortality in patients with CVD.^[37] It is also related to reduction of left ventricle mass after 6 months treatment.^[38] Dapagliflozin has minor effect on diastolic cardiac function of diabetic patients. Nevertheless, it is able to lower the risk of major adverse cardiovascular events in a diabetic patients with previous MI. ^[39]^[40]	Genitourinary infections^† Polyuria Volume depletion, hypotension, dizziness ↑ LDL-C ↑ Creatinine (transient) DKA, urinary tract infections leading to urosepsis, pyelonephritis	High
GLP-1 receptor agonists	Exenatide Exenatide extended release Liraglutide Albiglutide Lixisenatide Dulaglutide	Activates GLP-1 receptors	↑ Insulin secretion (glucose dependent) ↓ Glucagon secretion (glucose dependent) Slows gastric emptying ↑ Satiety	Rare hypoglycemia ↓ Weight ↓ Postprandial glucose excursions ↓ Some cardiovascular risk factors ↓ The chance of kidney disease progression, including the macroalbuminuria^[35] Liraglutide associated with lower CVD event rate and mortality in patients with CVD.^[37]	Gastrointestinal side effects (nausea/vomiting/diarrhea) ↑ Heart rate Acute pancreatitis C-cell hyperplasia/medullary thyroid tumors in animals Injectable Training requirements	High
Amylin mimetics	Pramlintide^§	Activates amylin receptors	↓ Glucagon secretion Slows gastric emptying ↑ Satiety	Postprandial glucose excursions ↓ Weight	Modest A1C efficacy Gastrointestinal side effects (nausea/vomiting) Hypoglycemia unless insulin dose is simultaneously reduced Injectable Frequent dosing schedule Training requirements	High
Insulins	Rapid-acting analogs Lispro Aspart Glulisine Inhaled insulin	Activates insulin receptors	↑ Glucose disposal ↓ Hepatic glucose production Suppresses ketogenesis	Nearly universal response Theoretically unlimited efficacy ↓ Microvascular risk	Hypoglycemia Weight gain Training requirements Patient and provider reluctance Injectable (except inhaled insulin) Pulmonary toxicity (inhaled insulin)	High
	Short-acting Human Regular
	Intermediate-acting Human NPH
	Basal insulin analogs Glargine Detemir Degludec
	Premixed insulin products NPH/Regular 70/30 70/30 aspart mix 75/25 lispro mix 50/50 lispro mix

^‡ Initial concerns regarding bladder cancer risk are decreasing after subsequent study.

^§ Not licensed in Europe for type 2 diabetes.

^† One study demonstrates factors like previous genital infection history, concurrent estrogen therapy and younger age as risk factors that augment the chance of this side effect. This study also reports chronic kidney disease and baseline DPP4 inhibitor therapy as factors that lower the risk of genital infection development.^[41]

Factors for Individualized Selection of Noninsulin Glucose-Lowering Medications in People with Type 2 Diabetes^[42]^a


Drug (glucose-lowering dose)	Glucose-lowering efficacy^[43]^[44],^b	Impact on weight^[44]^[45],^c	Hypoglycemia risk as monotherapy	Impact on comorbidities^d	Cost^[46],^f	Common adverse effects^[47],^g,^e	Practical considerations^[47]
Alpha-glucosidase inhibitors: Acarbose (25–100 mg orally at each meal) Miglitol (25–100 mg orally at each meal)	Intermediate (0.5%)	Neutral	No	Atherosclerotic cardiovascular disease: neutral^[48] HF^[49]: neutral^[50] 85	$–$$$	Most common adverse effects: abdominal pain (12%–19%), diarrhea (29%–31%), elevated transaminases (14% acarbose), flatulence (24%–74%) Contraindications: cirrhosis, inflammatory bowel disease, colonic ulceration, intestinal obstruction, hypersensitivity Warnings/precautions: hypoglycemia (add-on to sulfonylurea and/or insulin); use oral glucose (not sucrose) to treat hypoglycemia	Add-on treatment in individuals who require intermediate levels of HbA1c lowering (0.5%–1% above target); not as commonly used due to gastrointestinal adverse effects Can reduce postprandial hyperglycemia Dosing considerations: Take only when eating Start low dose, titrate slowly to minimize gastrointestinal adverse effects
Biguanides: Metformin (500–2000 mg orally daily)	High (1.0%–2.0%)	Neutral (potential for modest weight loss)	No	Atherosclerotic cardiovascular disease: likely long-term benefit^[51]^[52] Chronic kidney disease: neutral HF: neutral	$	Most common adverse effects^h: diarrhea (10%–53%), nausea/vomiting (7%–26%), abdominal discomfort (1%–6%) Contraindications: estimated glomerular filtration rate <30 mL/min/1.73 m², acute or chronic metabolic acidosis, hypersensitivity Warnings/precautions: vitamin B12 deficiency, lactic acidosis	When to use: First-line treatment when initial HbA1c <9%–10% and in absence of life-threatening hyperglycemic crisis (i.e., diabetic ketoacidosis or hyperosmolar hyperglycemic state) Can be used at reduced doses (i.e., 1000 mg) with estimated glomerular filtration rate 30–45 mL/min/1.73m² If gastrointestinal symptoms develop Hold or reduce dose to assess the relationship of symptoms to metformin Consider switching to extended-release formulation Take with food to improve tolerability and/or continue at reduced dose When to hold: Prior to procedure with nothing per mouth or illness Day of procedure Resume when eating normally
Dipeptidyl peptidase-4 inhibitors: Alogliptin (6.25–25 mg orally daily) Linagliptin (5 mg orally daily) Saxagliptin (2.5–5 mg orally daily) Sitagliptin (25–100 mg orally daily)	Intermediate (<0.5%)	Neutral	No	Atherosclerotic cardiovascular disease: neutral Chronic kidney disease: neutral HF: potential risk with saxagliptin^[53]	$$–$$$	Most common adverse effects: upper respiratory infection (4%–8%), nasopharyngitis (5%–7%), headache (4%–7%) Contraindications: hypersensitivity Warnings/precautions: pancreatitis, hypersensitivity reactions, arthralgia, bullous pemphigoid	When to use: Add-on treatment in individuals who require intermediate levels of HbA1c lowering (0.5%–1% above target) without risk of hypoglycemia For patients who desire to maintain weight Combination therapy: Dipeptidyl peptidase-4 inhibitors should not be combined with GLP-1RAs or dual GIP–GLP-1/GIP RAs because they act on the same pathway
GIP/GLP-1RA: Tirzepatide (2.5–15 mg subcutaneously once weekly)	High (1.0%–2.0%) to very high (2.0%–2.5%)	Loss (high)	No	Atherosclerotic cardiovascular disease: safe ⁱ Chronic kidney disease: safe ⁱ HF: benefit in obesity-related HFpEF^[54]	$$$$	Most common adverse effects: nausea (18%), diarrhea (17%), vomiting (9%), constipation (7%), dyspepsia (5%), abdominal pain (5%) Contraindications: personal or family history of medullary thyroid cancer or in patients with multiple endocrine neoplasia 2 Warnings/precautions: pancreatitis, hypoglycemia (add-on to sulfonylurea and/or insulin), diabetic retinopathy complications, acute kidney injury, hypersensitivity reactions, acute gallbladder disease	When to use: Add-on treatment in individuals taking ≥1 oral glucose-lowering drugs at maximally tolerated doses who require high to very high levels of HbA1c lowering (ie, HbA1c >1.0%–2.5% above goal) Can be used for patients who desire substantial weight loss When to hold: Prior to procedures, consider dietary adjustments (eg, liquid diet) or holding therapy (eg, day of procedure for daily formulations or 1 week prior for weekly formulations) in those at high risk for delayed gastric emptying When adding to insulin: Reduce then stop prandial insulin Reduce the basal insulin dose as GLP-1 dose increases, guided by glucose monitoring
GLP-1RAs: Dulaglutide (0.75–4.5 mg subcutaneously once weekly) Exenatide extended release (2 mg subcutaneously once weekly) Liraglutide (0.6–1.8 mg subcutaneously daily) Semaglutide (0.25–2 mg subcutaneously once weekly or 3–14 mg orally daily or 1.5–9 mg orally daily)	High (1.0%–2.0%) to very high (2.0%–2.5%)	Loss (intermediate to high)	No	Atherosclerotic cardiovascular disease: benefit on major cardiovascular events with dulaglutide,^[55] liraglutide,^[56] and semaglutide^[57]^[58] Chronic kidney disease: benefit on progression with semaglutide (subcutaneous)^[59] HF: evidence of benefit in obesity-related HFpEF with semaglutide (subcutaneous)^[60]^[61]	$$$$	Most common adverse effects^j: nausea (8%–21%), vomiting (3%–13%), diarrhea (9%–13%), abdominal pain (6%–11%), constipation (2%–5%) Contraindications: personal or family history of medullary thyroid cancer or in patients with multiple endocrine neoplasia 2 Warnings/precautions: pancreatitis, hypoglycemia (add-on to sulfonylurea and/or insulin), diabetic retinopathy complications, acute kidney injury, hypersensitivity reactions, acute gallbladder disease	When to use: First-line treatment in atherosclerotic cardiovascular disease, chronic kidney disease, obesity-related HFpEF Add-on treatment in individuals without cardiovascular or kidney comorbidities taking 1 or more oral glucose-lowering drugs at maximally tolerated doses who require high to very high levels of HbA1c lowering (ie, HbA1c level >1.0%–2.5% above goal) Can be used for patients who desire moderate weight loss When to hold: Prior to procedures, consider dietary adjustments (eg, liquid diet) or holding therapy (eg, day of procedure for daily formulations or 1 week prior for weekly formulations) in those at high risk for delayed gastric emptying Switching GLP-1 formulations: Although there is no standard dose equivalence, the following may be used as a guide: semaglutide oral 14 mg → semaglutide subcutaneous 0.5 mg → dulaglutide 1.5 mg → liraglutide 1.8 mg → tirzepatide 2.5 mg^[62]^[63] When adding to insulin: Reduce, then stop prandial insulin Reduce the basal insulin dose as GLP-1 dose increases, guided by glucose monitoring
Meglitinides: Nateglinide (60–120 mg orally at each meal) Repaglinide (0.5–2 mg orally at each meal)	High (1%–2%)	Gain	Yes	Atherosclerotic cardiovascular disease: neutral^[64] HF: neutral^[64]	$	Most common adverse effects: hypoglycemia (up to 31%), upper respiratory infection (11%–16%), back pain (4%–5%), flu‑like symptoms (4% [nateglinide]), arthropathy (3%–6%), diarrhea (3%–5%) Contraindications: hypersensitivity Warnings/precautions: hypoglycemia	When to use: Add‑on treatment in individuals who require high levels of HbA1c lowering (1%–2% above target); not as commonly used due to multiple daily dosing and risk of hypoglycemia Can reduce postprandial hyperglycemia When to hold: Hold day of procedure; resume when eating normally
SGLT2 inhibitors^k: Bexagliflozin (20 mg orally daily) Canagliflozin (100–300 mg orally daily) Dapagliflozin (5–10 mg orally daily) Empagliflozin (10–25 mg orally daily) Ertugliflozin (5–15 mg orally daily)	Intermediate (0.5%)	Loss (intermediate)	No	Atherosclerotic cardiovascular disease: benefit on major cardiovascular events with canagliflozin^[65] and empagliflozin^[66] Chronic kidney disease: benefit on progression with canagliflozin,^[67] dapagliflozin,^[68] and empagliflozin^[69] HF: benefit in HFpEF and HFrEF with dapagliflozin^[70],^[71],^[72] and empagliflozin^[73],^[74]	$–$$$	Most common adverse effects: genital mycotic infections (6%–12%), urinary tract infection (4%–8%), increased urination (2%–7%) Contraindications: hypersensitivity Warnings/precautions: euglycemic diabetic ketoacidosis, volume depletion, severe urinary tract infections, hypoglycemia (add‑on to sulfonylurea and/or insulin), Fournier gangrene; lower limb amputation, fractures with canagliflozin	When to use: First‑line treatment in atherosclerotic cardiovascular disease, chronic kidney disease, HF Add‑on treatment in individuals without cardiovascular or kidney comorbidities who require intermediate levels of HbA1c lowering (0.5%–1% above target) Can be used for patients who desire moderate weight loss When to hold: Hold 3–4 d prior to procedures Consider holding if risk of dehydration (eg, religious fasting, strenuous exercise on hot day)
Sulfonylureas: Glimepiride (1–8 mg orally daily) Glipizide (IR: 2.5–40 mg orally daily; ER: 2.5–20 mg orally daily) Glyburide (1.25–20 mg orally daily)	High (1%–2%)	Gain	Yes	Atherosclerotic cardiovascular disease: neutral Chronic kidney disease: neutral HF: neutral	$	Most common adverse effects (glimepiride^e): hypoglycemia (20%), headache (8%), nausea (5%), dizziness (5%) Contraindication: hypersensitivity Warnings/precautions: severe hypoglycemia risk, hemolytic anemia (G6PD deficiency), special warning for increased cardiovascular mortality with older‑generation sulfonylurea (tolbutamide); glimepiride demonstrated safety^[75]	When to use: Add‑on treatment in individuals who require high levels of HbA1c lowering (1%–2% above target) Inexpensive and can be used when cost is a concern When to hold: Day of procedure; resume when eating normally To minimize hypoglycemia: In those at higher risk (eg, older adults, chronic kidney disease), do not use glyburide, which is longer‑acting and associated with higher hypoglycemia risk vs other sulfonylureas Glimepiride or glipizide are shorter‑acting and preferred Dose cautiously; do not overtreat
Thiazolidinedione: Pioglitazone (15–45 mg orally daily)	High (1%–2%)	Gain	No	Atherosclerotic cardiovascular disease: likely benefit^[76],^[77] Chronic kidney disease: neutral HF: increased risk	$	Most common adverse effects: upper respiratory infection (13%), headache (9%), sinusitis (6%), myalgia (5%), pharyngitis (5%) Contraindications: New York Heart Association class III or IV HF, hypersensitivity Warnings/precautions: HF, liver toxicity, bladder cancer, fluid retention/edema, fractures, macular edema	When to use: Add‑on treatment in individuals who require high levels of HbA1c lowering (1%–2% above target) Inexpensive, can be used when cost is a concern Dosing considerations^[78]: Benefits maximized and adverse effects minimized at doses of 15 or 30 mg Weight gain, edema, and heart failure risk higher at 45‑mg dose Fracture risk similar across all doses

Abbreviations: GIP, glucose-dependent insulinotropic polypeptide; GLP-1RA, glucagon-like peptide-1 receptor agonist; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; SGLT, sodium-glucose cotransporter.

a: Commonly used classes of medications currently approved in the US for treatment of type 2 diabetes. b: Based on mean hemoglobin A1c (HbA1C) reductions from baseline in clinical trials of drug-naive patients with type 2 diabetes. Individualized glycemic responses vary based on starting HbA1C and other patient factors. c: Relative weight loss effect: modest, <5%loss from baseline; intermediate, 5%-10%; high, >10%. d: Specific agents have evidence of benefit from dedicated outcome trials. e: Rates listed are taken from the glimepiride package insert. Specific rates not provided for glyburide and glipizide. f: From National Average Drug Acquisition Cost data. Based on the price of a 30-day supply at the maximum recommended dose. $ = $1-100/mo; $$ = $101-300/mo; $$$ = $301-600/mo; $$$$ = >$600/mo. g: Derived from product package insert; ranges for frequency of common adverse effects at highest indicated dose are provided by class unless otherwise indicated. Refer to product-specific labeling for specific rates. h: Gastrointestinal adverse event rates across the range of doses for metformin include immediate release and extended-release products; extended-release products are associated with lower rates of diarrhea, nausea, and vomiting. Consider periodic screening for B12 deficiency.^[79] i: Cardiovascular and kidney outcome trials are ongoing. j: Gastrointestinal adverse event rates are for doses approved by the US Food and Drug Administration for glucose lowering. Higher doses for weight loss are associated with higher rates of nausea and vomiting. k: Sotagliflozin is a SGLT1/2 inhibitor indicated to reduce the risk of cardiovascular death, hospitalization for HF, and urgent HF visits in adults with HF or type 2 diabetes, CKD, and other cardiovascular risk factors; it is not currently indicated for glucose lowering in type 2 diabetes and thus not included.^[80]

Factors for Individualized Selection of Insulin therapy in People with Type 2 Diabetes^[42]^a


Drug class and agents^b	Usual dosing range for glucose-lowering^[47]	Glucose-lowering efficacy	Cost^[46]	Safety/tolerability^[47]	Considerations for dosing and titration^[79]^[81]	Practical considerations
Basal insulin: Human NPH Degludec Glargine glargine biosimilar (glargine-yfgn, glargine-aglr) and follow-on products	Typically up to 200–300 units; above this, consider concentrated insulins	In theory, no limit to HbA1c lowering potential	$ - $$$ Human insulin (NPH, regular) is lower cost than analog insulins; follow-on and biosimilar insulins often lower cost than the reference insulin product	Most common adverse effects: Hypoglycemia Injection site reactions Lipohypertrophy or lipoatrophy Weight gain Contraindications: Hypersensitivity Warnings/precautions: Never share insulin delivery devices between patients, even if the needle is changed Increased risk of fluid retention/edema; risk increased further when used in combination with thiazolidinediones	Adding basal insulin: Start 10 units or 0.1–0.2 units/kg/d Increase 2 units every 3 days until FPG target without overtight or midday hypoglycemia If not already on GLP‑1RA or dual GLP‑1/GIP RA, consider adding	When to use: First-line treatment with severe hyperglycemic symptoms (ie, polyuria or polydipsia) and life-threatening hyperglycemic crisis (ie, diabetic ketoacidosis or hyperosmolar hyperglycemic state) and/or HbA1c >10% Add-on treatment for individuals taking 1 or more oral glucose-lowering drugs at maximally tolerated doses who require injectable therapies to meet glycemic targets (ie, HbA1c level more than 1.5%–2% above goal) Basal insulin can be used to target elevated fasting glucose levels (ie, >80–130 mg/dL)
Bolus insulin: Human regular Aspart Aspart biosimilar (aspart-szjj) Fast-acting aspart Lispro Lispro biosimilar (lispro-aabc) and follow-on products Glulisine Inhaled insulin					Adding prandial insulin: Start with 4 units (or 10% of basal dose) to the largest meal of the day, titrate based on response, then add additional injections in step-wise manner to second and third meals Titrate by 1–2 units (10%–15%) twice weekly Consider premixed insulin in people with meal patterns that may benefit mismatching (eg, large breakfast and supper, small mid-day meal)	Prandial insulin can be used to target elevated postprandial glucose levels within 1–2 h after meal (ie, >180 mg/dL)
Premixed insulin: Aspart 70/30 Aspart 75/25 Lispro 50/50 NPH/regular 70/30					Switching insulin formulations: If close to glycemic target: Sum the total daily dose and reduce by 10%, then titrate based on glucose monitoring If well above glycemic target: Switch total daily equivalent dose, then titrate Anticipate total daily insulin dose reduction with treatment of glucose toxicity and resolution of insulin resistance as counter-regulatory hormone levels and volume depletion resolve
Fixed dose combinations: Degludec/liraglutide Glargine/lixisenatide					Impact on key comorbidities: Neutral cardiovascular^[82] and kidney effects Hypoglycemia: Analog insulins generally have less hypoglycemia than human insulins When to hold: If nothing per mouth, hold or reduce prandial insulin by 50%–80% to weight-based basal requirement (eg, 0.2–0.3 units/kg ideal body weight)

Abbreviations: FPG, fasting plasma glucose; GIP, glucose-dependent insulinotropic polypeptide; GLP-1RA, glucagon-like peptide-1 receptor agonist; kg, kilograms; NPH, neutral protamine Hagedorn; NPO, nothing per mouth.

a: Most insulins available on the market are U-100 concentration (U-100 = 100 units of insulin/mL solution). Concentrated insulins include U-200 insulin degludec or U-200 insulin lispro (U-200 = 200 units of insulin/mL solution), U-300 insulin glargine (U-300 = 300 units of insulin/mL solution), and U-500 regular insulin (U-500 = 500 units of insulin/mL solution). Concentrated insulins can be used to reduce injection volume in individuals on high insulin doses. b: “Follow-on insulins” broadly refers to copies of an original insulin; “biosimilar insulin” is a specific type of follow-on insulin that has undergone rigorous testing to demonstrate it is highly similar to the reference insulin with no clinically meaningful differences in safety and effectiveness. c: Cost information is derived from National Average Drug Acquisition Cost (NADAC) data. Cost ratings are based on the price of a 30-day (1-month) supply at the maximum recommended dose. $ = $1-100/mo; $$ = $101-300/mo; $$$ = $301-600/mo; $$$$ = >$600/mo. d: Derived from product package insert information.

Current Clinical Practice Recommendations For Management of Type 2 Diabetes From Major Professional Societies^[42]^,a


Category	American Diabetes Association (2025)^[79]	American Association of Clinical Endocrinology (2023)^[83]	Endocrine Society (older adults, 2019)^[84]	American College of Physicians (2024)^[85],^[86]	VA/DoD (US Department of Veterans Affairs/Department of Defense) (2023)^[87]	Diabetes Canada (2024)^[88]	National Institute for Health and Care Excellence (UK) (2022)^[89]	World Health Organization (2018)^[90]	International Diabetes Federation (2025)^[91]
HbA1c or glucose target for nonpregnant adults (general population)	<7%, individualize <6.5% younger, short duration, if achieved safely <8% older, multiple comorbidities	≤6.5% or as close to normal as is safe and achievable for patients 7%-8% if high risk for hypoglycemia or limited life expectancy	7.5% to 8.5% depending on health status; minimize hypoglycemia	7%-8%, intensify if <6%	≤8.5%, individualize	≤6.5% for adults if low risk of hypoglycemia ≤7.0% most adults 7.1%-8.0% functionally dependent 7.1%-8.5% frail elderly and/or dementia Recurrent severe hypoglycemia Hypoglycemia unawareness Limited life expectancy	<7% on medication, individualize, maintain lower target if achieved without hypoglycemia	<7% when available, otherwise fasting blood glucose <126 mg/dL (individualize)	General target <7.0% Personalize HbA1c target: higher in older adults and lower in those newly diagnosed If HbA1c assay not available, use any available glucose measure
Healthy lifestyle behaviors	Recommended	Recommended	Recommended	Recommended	Recommended	Recommended	Recommended	Recommended	Recommended
First-line medication	Metformin or other agents and combination therapies that provide adequate efficacy to attain HbA1c goals. Use SGLT2i or GLP-1RA with cardiovascular or kidney benefit in the presence of those comorbidities^b	Metformin in absence of cardiovascular or kidney comorbidities^b Use SGLT2i or GLP-1RA with cardiovascular or kidney benefit in the presence of those comorbidities^b	Metformin if tolerated in older adults	Metformin	Based on cardiovascular and kidney comorbidities, efficacy and risk-benefit ratio of each medication class	Metformin	Metformin	Metformin	Metformin In obese persons, consider metformin and GLP-1 RA (optimal care) or metformin and SGLT2i (basic care; SGLT2i available in many low- and middle-income countries at affordable cost)
Cardiovascular and kidney protective SGLT2i or GLP-1RA in those with ASCVD or high-risk ASCVD^c	Recommended Independent of HbA1c	Recommended Independent of HbA1c	Recommended	Recommended And, add as next step after metformin for inadequate glycemic control (regardless of comorbidities)	Recommended Independent of HbA1c	Recommended ASCVD: SGLT2i High risk for ASCVD: consider SGLT2i	Recommended Independent of HbA1c	Recommended	Recommended GLP-1 RA or SGLT2i (optimal care) SGLT2i (basic care) And, add as next step after metformin for inadequate glycemic control (regardless of comorbidities)
SGLT2i in those with HF or CKD^c	Recommended Independent of HbA1c Recommend SGLT2i or GLP-1RA with proven benefit in CKD SGLT2i preferred in HF	Recommended Independent of HbA1c Recommend SGLT2i or GLP-1RA with proven benefit in CKD SGLT2i preferred in HF	Recommended Prioritize adding SGLT2i for CKD or HF	Recommended Independent of HbA1c Recommend SGLT2i with proven benefit in CKD but can also consider GLP-1 RA SGLT2i preferred in HF	Recommended Independent of HbA1c Recommend SGLT2i with proven benefit in CKD but can also consider GLP-1RA SGLT2i preferred in HF	Recommended HF: SGLT2i add to metformin CKD, use SGLT2i if receiving ACEi or ARB or UACR >30 mg/g	Recommended	Recommended	Recommended Cardiorenal: GLP-1 RA or SGLT2i (optimal care) Cardiorenal: SGLT2i (basic care) SGLT2i preferred in HF
Combination SGLT2i and GLP-1RA in those with ASCVD or high ASCVD risk	If not at glycemic target	If not at glycemic target	Consider	Consider	If not at glycemic target	Consider
When to initiate injectable therapy (ie, GLP-1RA, dual GLP-1/GIP RA, or insulin) to meet glycemic targets	GLP-1RA or dual GLP-1/GIP RA are preferred to insulin for persistent hyperglycemia as initial injectable Consider insulin initially with: evidence of ongoing catabolism; symptomatic hyperglycemia; HbA1c >10% and/or glucose >300 mg/dL	If not at target at <3 mo, GLP-1RA as first injectable; if HbA1c >10% and/or glucose >300 mg/dL with symptomatic hyperglycemia, or not at glycemic target, start basal insulin with or without GLP-1RA	Use insulin and sulfonylurea sparingly in older adults	Initiate insulin for symptomatic hyperglycemia and/or metabolic decompensation	Ineffective dual oral therapy: Start NPH Use analogue insulin if hypoglycemia on NPH Start basal bolus or premixed insulin for HbA1c ≥9% GLP-1RA for BMI ≥35 or <35 with comorbidities. Stop insulin if HbA1c reduction <1% and weight loss target not met	Start human insulin if goal not achieved on metformin and sulfonylurea; consider long-acting insulin analogues if frequent, severe hypoglycemia on human insulin	Begin insulin therapy when optimized available glucose-lowering medications and lifestyle interventions do not maintain target blood glucose control Commence with single daily injection of basal analog insulin (optimal care) or affordable human, analog, or biosimilar insulin (basic care)
Additional recommendations	Strong weight and comorbidity focus^b	Strong weight and comorbidity focus^b Alternate algorithms for “complication-” or “glucose-” centric approaches; focus on rapid goal attainment GLP-1 RA or pioglitazone for stroke	Assess overall health and values to determine treatments and targets; simplify medication and relax targets with cognitive impairment	Do not add DPP-4i to metformin to reduce morbidity or all-cause mortality Discontinue insulin or sulfonylurea when possible; insulin and sulfonylurea are inferior to SGLT2i and GLP-1RA for morbidity and all-cause mortality but may still have beneficial value for glycemic control	Strong comorbidity focus^b Deprioritize insulin, sulfonylurea, and meglitinide especially >64 y	Strong comorbidity focus^b Initial combination therapy with metformin and second agent if HbA1c ≥1.5% above target	Second line: DPP-4i or pioglitazone or SGLT2i If insulin is unsuitable (after metformin and/or sulfonylurea), a DPP-4 inhibitor, an SGLT-2 inhibitor, or a thiazolidinedione may be added	Target population is low-resource settings in low- or high-income countries	Describes 2 levels of care: “Optimal care” sets the standard for evidence-based care which ideally would be universally implemented “Basic care” aims to achieve the same objectives but is provided in a healthcare setting with limited resources

Abbreviations: DPP4i, DPP-4 inhibitor; NPH, neutral protamine Hagedorn insulin.

a: Cells are blank if the topic is not explicitly addressed by the guideline. b: Comorbidities include atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). c: Medications with demonstrated cardiovascular or kidney benefit within each class are preferred when used for this indication. For SGLT2i, these include canagliflozin, dapagliflozin and empagliflozin. For GLP-1RA, these include dulaglutide, liraglutide, and semaglutide.

References

↑ Shi Q, Nong K, Vandvik PO, Guyatt GH, Schnell O, Rydén L; et al. (2023). "Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials". BMJ. 381: e074068. doi:10.1136/bmj-2022-074068. PMC 10077111 Check |pmc= value (help). PMID 37024129 Check |pmid= value (help).
↑ Qaseem A, Hopkins RH, Sweet DE, Starkey M, Shekelle P (2013). "Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: A clinical practice guideline from the American College of Physicians". Ann. Intern. Med. 159 (12): 835–47. doi:10.7326/0003-4819-159-12-201312170-00726. PMID 24145991.
↑ "Standards of Medical Care in Diabetes-2017: Summary of Revisions". Diabetes Care. 40 (Suppl 1): S4–S5. 2017. doi:10.2337/dc17-S003. PMID 27979887.
↑ Colagiuri S, Cull CA, Holman RR (2002). "Are lower fasting plasma glucose levels at diagnosis of type 2 diabetes associated with improved outcomes?: U.K. prospective diabetes study 61". Diabetes Care. 25 (8): 1410–7. PMID 12145243.
↑ Davidson MB (1992). "Successful treatment of markedly symptomatic patients with type II diabetes mellitus using high doses of sulfonylurea agents". West. J. Med. 157 (2): 199–200. PMC 1011263. PMID 1441492.
↑ ^6.0 ^6.1 Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, Chu Y, Iyoha E, Segal JB, Bolen S (2016). "Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis". Ann. Intern. Med. 164 (11): 740–51. doi:10.7326/M15-2650. PMID 27088241.
↑ Palmer SC, Mavridis D, Nicolucci A, Johnson DW, Tonelli M, Craig JC, Maggo J, Gray V, De Berardis G, Ruospo M, Natale P, Saglimbene V, Badve SV, Cho Y, Nadeau-Fredette AC, Burke M, Faruque L, Lloyd A, Ahmad N, Liu Y, Tiv S, Wiebe N, Strippoli GF (2016). "Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis". JAMA. 316 (3): 313–24. doi:10.1001/jama.2016.9400. PMID 27434443.
↑ GitHub Contributors. Hypertonic Saline for Bronchiolitis: a living systematic review. GitHub. Available at http://openmetaanalysis.github.io/Diabetes-mellitus-type-2-mortality-prevention-with-pharmacotherapy/. Accessed June 11, 2018.
↑ Mesinovic J, Zengin A, De Courten B, Ebeling PR, Scott D (2019). "Sarcopenia and type 2 diabetes mellitus: a bidirectional relationship". Diabetes Metab Syndr Obes. 12: 1057–1072. doi:10.2147/DMSO.S186600. PMC 6630094 Check |pmc= value (help). PMID 31372016.
↑ Eurich, Dean T.; Weir, Daniala L.; Majumdar, Sumit R.; Tsuyuki, Ross T.; Johnson, Jeffrey A.; Tjosvold, Lisa; Vanderloo, Saskia E.; McAlister, Finlay A. (2013). "Comparative Safety and Effectiveness of Metformin in Patients With Diabetes Mellitus and Heart Failure". Circulation: Heart Failure. 6 (3): 395–402. doi:10.1161/CIRCHEARTFAILURE.112.000162. ISSN 1941-3289.
↑ Mendy A, Gopal R, Alcorn JF, Forno E (2019). "Reduced mortality from lower respiratory tract disease in adult diabetic patients treated with metformin". Respirology. 24 (7): 646–651. doi:10.1111/resp.13486. PMC 6579707 Check |pmc= value (help). PMID 30761687.
↑ Liang, Huoyan; Ding, Xianfei; Li, Lifeng; Wang, Tian; Kan, Quancheng; Wang, Lexin; Sun, Tongwen (2019). "Association of preadmission metformin use and mortality in patients with sepsis and diabetes mellitus: a systematic review and meta-analysis of cohort studies". Critical Care. 23 (1). doi:10.1186/s13054-019-2346-4. ISSN 1364-8535.
↑ Singh, Awadhesh Kumar; Khunti, Kamlesh (2020). "Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review". Diabetes Research and Clinical Practice. 165: 108266. doi:10.1016/j.diabres.2020.108266. ISSN 0168-8227.
↑ Wu, Yingjie; Zhou, An; Tang, Li; Lei, Yuanyuan; Tang, Bo; Zhang, Linjing (2020). "Bile Acids: Key Regulators and Novel Treatment Targets for Type 2 Diabetes". Journal of Diabetes Research. 2020: 1–11. doi:10.1155/2020/6138438. ISSN 2314-6745.
↑ Sulkin TV, Bosman D, Krentz AJ (1997). "Contraindications to metformin therapy in patients with NIDDM". Diabetes Care. 20 (6): 925–8. doi:10.2337/diacare.20.6.925. PMID 9167101.
↑ Holstein A, Stumvoll M (2005). "Contraindications can damage your health--is metformin a case in point?". Diabetologia. 48 (12): 2454–9. doi:10.1007/s00125-005-0026-1. PMID 16283245.
↑ Garber AJ, Duncan TG, Goodman AM, Mills DJ, Rohlf JL (1997). "Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose-response trial". Am J Med. 103 (6): 491–7. doi:10.1016/s0002-9343(97)00254-4. PMID 9428832.
↑ Herkert D, Vijayakumar P, Luo J, Schwartz JI, Rabin TL, DeFilippo E; et al. (2018). "Cost-Related Insulin Underuse Among Patients With Diabetes". JAMA Intern Med. doi:10.1001/jamainternmed.2018.5008. PMID 30508012.
↑ Greene JA, Riggs KR (2015). "Why is there no generic insulin? Historical origins of a modern problem". N Engl J Med. 372 (12): 1171–5. doi:10.1056/NEJMms1411398. PMID 25785977.
↑ Luo J, Khan NF, Manetti T, Rose J, Kaloghlian A, Gadhe B; et al. (2019). "Implementation of a Health Plan Program for Switching From Analogue to Human Insulin and Glycemic Control Among Medicare Beneficiaries With Type 2 Diabetes". JAMA. 321 (4): 374–384. doi:10.1001/jama.2018.21364. PMID 30694321.
↑ ^21.0 ^21.1 ^21.2 Lipska KJ, Parker MM, Moffet HH, Huang ES, Karter AJ (2018). "Association of Initiation of Basal Insulin Analogs vs Neutral Protamine Hagedorn Insulin With Hypoglycemia-Related Emergency Department Visits or Hospital Admissions and With Glycemic Control in Patients With Type 2 Diabetes". JAMA. 320 (1): 53–62. doi:10.1001/jama.2018.7993. PMC 6134432. PMID 29936529.
↑ ^22.0 ^22.1 Horvath K, Jeitler K, Berghold A, Ebrahim SH, Gratzer TW, Plank J; et al. (2007). "Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus". Cochrane Database Syst Rev (2): CD005613. doi:10.1002/14651858.CD005613.pub3. PMID 17443605. Review in: ACP J Club. 2007 Sep-Oct;147(2):46
↑ Mesinovic J, Zengin A, De Courten B, Ebeling PR, Scott D (2019). "Sarcopenia and type 2 diabetes mellitus: a bidirectional relationship". Diabetes Metab Syndr Obes. 12: 1057–1072. doi:10.2147/DMSO.S186600. PMC 6630094 Check |pmc= value (help). PMID 31372016.
↑ Esposito K; et al. (2008). "Addition of neutral protamine lispro insulin or insulin glargine to oral type 2 diabetes regimens for patients with suboptimal glycemic control: a randomized trial". Ann Intern Med. 149: 531–9. PMID 18936501.
↑ Holman RR; et al. (2007). "Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes". N Engl J Med. 357: 1716–30. doi:10.1056/NEJMoa075392. PMID 17890232.
↑ Qayyum R, Bolen S, Maruthur N, Feldman L, Wilson LM, Marinopoulos SS; et al. (2008). "Systematic review: comparative effectiveness and safety of premixed insulin analogues in type 2 diabetes". Ann Intern Med. 149 (8): 549–59. PMC 4762020. PMID 18794553.
↑ ^27.0 ^27.1 ^27.2 Yki-Järvinen H, Kauppila M, Kujansuu E; et al. (1992). "Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus". N. Engl. J. Med. 327 (20): 1426–33. PMID 1406860.
↑ ^28.0 ^28.1 ^28.2 Yki-Järvinen H, Ryysy L, Nikkilä K, Tulokas T, Vanamo R, Heikkilä M (1999). "Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial". Ann. Intern. Med. 130 (5): 389–96. PMID 10068412.
↑ Semlitsch T, Engler J, Siebenhofer A, Jeitler K, Berghold A, Horvath K (2020). "(Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus". Cochrane Database Syst Rev. 11: CD005613. doi:10.1002/14651858.CD005613.pub4. PMC 8095010 Check |pmc= value (help). PMID 33166419 Check |pmid= value (help).
↑ Kratz A, Lewandrowski KB (1998). "Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Normal reference laboratory values". N. Engl. J. Med. 339 (15): 1063–72. PMID 9761809.
↑ Russell-Jones D, Dauchy A, Delgado E, Dimitriadis G, Frandsen HA, Popescu L; et al. (2019). "Take Control: A randomized trial evaluating the efficacy and safety of self- versus physician-managed titration of insulin glargine 300 U/mL in patients with uncontrolled type 2 diabetes". Diabetes Obes Metab. 21 (7): 1615–1624. doi:10.1111/dom.13697. PMC 6767413 Check |pmc= value (help). PMID 30851006.
↑ Novo Nordisk has partnerships to provide low-cost human insulin. Available at https://www.novocare.com/diabetes-overview/let-us-help/human-insulin-options.html
↑ Fonseca V, Rosenstock J, Patwardhan R, Salzman A (2000). "Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial". JAMA. 283 (13): 1695–702. doi:10.1001/jama.283.13.1695. PMID 10755495.
↑ Singh, Awadhesh Kumar; Khunti, Kamlesh (2020). "Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review". Diabetes Research and Clinical Practice. 165: 108266. doi:10.1016/j.diabres.2020.108266. ISSN 0168-8227.
↑ ^35.0 ^35.1 Zelniker, Thomas A.; Wiviott, Stephen D.; Raz, Itamar; Im, KyungAh; Goodrich, Erica L.; Furtado, Remo H.M.; Bonaca, Marc P.; Mosenzon, Ofri; Kato, Eri T.; Cahn, Avivit; Bhatt, Deepak L.; Leiter, Lawrence A.; McGuire, Darren K.; Wilding, John P.H.; Sabatine, Marc S. (2019). "Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus". Circulation. 139 (17): 2022–2031. doi:10.1161/CIRCULATIONAHA.118.038868. ISSN 0009-7322.
↑ Palmer, Suetonia C; Tendal, Britta; Mustafa, Reem A; Vandvik, Per Olav; Li, Sheyu; Hao, Qiukui; Tunnicliffe, David; Ruospo, Marinella; Natale, Patrizia; Saglimbene, Valeria; Nicolucci, Antonio; Johnson, David W; Tonelli, Marcello; Rossi, Maria Chiara; Badve, Sunil V; Cho, Yeoungjee; Nadeau-Fredette, Annie-Claire; Burke, Michael; Faruque, Labib I; Lloyd, Anita; Ahmad, Nasreen; Liu, Yuanchen; Tiv, Sophanny; Millard, Tanya; Gagliardi, Lucia; Kolanu, Nithin; Barmanray, Rahul D; McMorrow, Rita; Raygoza Cortez, Ana Karina; White, Heath; Chen, Xiangyang; Zhou, Xu; Liu, Jiali; Rodríguez, Andrea Flores; González-Colmenero, Alejandro Díaz; Wang, Yang; Li, Ling; Sutanto, Surya; Solis, Ricardo Cesar; Díaz González-Colmenero, Fernando; Rodriguez-Gutierrez, René; Walsh, Michael; Guyatt, Gordon; Strippoli, Giovanni F M (2021). "Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials". BMJ: m4573. doi:10.1136/bmj.m4573. ISSN 1756-1833.
↑ ^37.0 ^37.1 Paneni F, Lüscher TF (2017). "Cardiovascular Protection in the Treatment of Type 2 Diabetes: A Review of Clinical Trial Results Across Drug Classes". Am J Cardiol. 120 (1S): S17–S27. doi:10.1016/j.amjcard.2017.05.015. PMID 28606340.
↑ Verma, Subodh; Mazer, C. David; Yan, Andrew T.; Mason, Tamique; Garg, Vinay; Teoh, Hwee; Zuo, Fei; Quan, Adrian; Farkouh, Michael E.; Fitchett, David H.; Goodman, Shaun G.; Goldenberg, Ronald M.; Al-Omran, Mohammed; Gilbert, Richard E.; Bhatt, Deepak L.; Leiter, Lawrence A.; Jüni, Peter; Zinman, Bernard; Connelly, Kim A. (2019). "Effect of Empagliflozin on Left Ventricular Mass in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease". Circulation. 140 (21): 1693–1702. doi:10.1161/CIRCULATIONAHA.119.042375. ISSN 0009-7322.
↑ Furtado, Remo H.M.; Bonaca, Marc P.; Raz, Itamar; Zelniker, Thomas A.; Mosenzon, Ofri; Cahn, Avivit; Kuder, Julia; Murphy, Sabina A.; Bhatt, Deepak L.; Leiter, Lawrence A.; McGuire, Darren K.; Wilding, John P.H.; Ruff, Christian T.; Nicolau, Jose C.; Gause-Nilsson, Ingrid A.M.; Fredriksson, Martin; Langkilde, Anna Maria; Sabatine, Marc S.; Wiviott, Stephen D. (2019). "Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction". Circulation. 139 (22): 2516–2527. doi:10.1161/CIRCULATIONAHA.119.039996. ISSN 0009-7322.
↑ Eickhoff, Mie K.; Olsen, Flemming J.; Frimodt-Møller, Marie; Diaz, Lars J.; Faber, Jens; Jensen, Magnus T.; Rossing, Peter; Persson, Frederik (2020). "Effect of dapagliflozin on cardiac function in people with type 2 diabetes and albuminuria – A double blind randomized placebo-controlled crossover trial". Journal of Diabetes and its Complications. 34 (7): 107590. doi:10.1016/j.jdiacomp.2020.107590. ISSN 1056-8727.
↑ Nakhleh, Afif; Zloczower, Moshe; Gabay, Linoy; Shehadeh, Naim (2020). "Effects of sodium glucose co-transporter 2 inhibitors on genital infections in female patients with type 2 diabetes mellitus– Real world data analysis". Journal of Diabetes and its Complications. 34 (7): 107587. doi:10.1016/j.jdiacomp.2020.107587. ISSN 1056-8727.
↑ ^42.0 ^42.1 ^42.2 Kalyani RR, Neumiller JJ, Maruthur NM, Wexler DJ (September 2025). "Diagnosis and Treatment of Type 2 Diabetes in Adults: A Review". JAMA. 334 (11): 984–1002. doi:10.1001/jama.2025.5956. PMID 40549398 Check |pmid= value (help).
↑ Tsapas A, Avgerinos I, Karagiannis T, Malandris K, Manolopoulos A, Andreadis P, Liakos A, Matthews DR, Bekiari E (August 2020). "Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis". Ann Intern Med. 173 (4): 278–286. doi:10.7326/M20-0864. PMID 32598218 Check |pmid= value (help).
↑ ^44.0 ^44.1 Karagiannis T, Avgerinos I, Liakos A, Del Prato S, Matthews DR, Tsapas A, Bekiari E (August 2022). "Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis". Diabetologia. 65 (8): 1251–1261. doi:10.1007/s00125-022-05715-4. PMC 9112245 Check |pmc= value (help). PMID 35579691 Check |pmid= value (help).
↑ Tsapas A, Karagiannis T, Kakotrichi P, Avgerinos I, Mantsiou C, Tousinas G, Manolopoulos A, Liakos A, Malandris K, Matthews DR, Bekiari E (September 2021). "Comparative efficacy of glucose-lowering medications on body weight and blood pressure in patients with type 2 diabetes: A systematic review and network meta-analysis". Diabetes Obes Metab. 23 (9): 2116–2124. doi:10.1111/dom.14451. PMID 34047443 Check |pmid= value (help).
↑ ^46.0 ^46.1 "CMS Medicaid Data".
↑ ^47.0 ^47.1 ^47.2 ^47.3 "Micromedex Products: Please Login".
↑ Echouffo-Tcheugui JB, Perreault L, Ji L, Dagogo-Jack S (April 2023). "Diagnosis and Management of Prediabetes: A Review". JAMA. 329 (14): 1206–1216. doi:10.1001/jama.2023.4063. PMID 37039787 Check |pmid= value (help).
↑ Wysham C, Shubrook J (November 2020). "Beta-cell failure in type 2 diabetes: mechanisms, markers, and clinical implications". Postgrad Med. 132 (8): 676–686. doi:10.1080/00325481.2020.1771047. PMID 32543261 Check |pmid= value (help).
↑ Holman RR, Coleman RL, Chan JC, Chiasson JL, Feng H, Ge J, Gerstein HC, Gray R, Huo Y, Lang Z, McMurray JJ, Rydén L, Schröder S, Sun Y, Theodorakis MJ, Tendera M, Tucker L, Tuomilehto J, Wei Y, Yang W, Wang D, Hu D, Pan C (November 2017). "Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial". Lancet Diabetes Endocrinol. 5 (11): 877–886. doi:10.1016/S2213-8587(17)30309-1. PMID 28917545.
↑ Adler AI, Coleman RL, Leal J, Whiteley WN, Clarke P, Holman RR (July 2024). "Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91)". Lancet. 404 (10448): 145–155. doi:10.1016/S0140-6736(24)00537-3. PMID 38772405 Check |pmid= value (help).
↑ Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA (October 2008). "10-year follow-up of intensive glucose control in type 2 diabetes". N Engl J Med. 359 (15): 1577–89. doi:10.1056/NEJMoa0806470. PMID 18784090.
↑ Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I (October 2013). "Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus". N Engl J Med. 369 (14): 1317–26. doi:10.1056/NEJMoa1307684. PMID 23992601.
↑ Packer M, Zile MR, Kramer CM, Baum SJ, Litwin SE, Menon V, Ge J, Weerakkody GJ, Ou Y, Bunck MC, Hurt KC, Murakami M, Borlaug BA (January 2025). "Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity". N Engl J Med. 392 (5): 427–437. doi:10.1056/NEJMoa2410027. PMID 39555826 Check |pmid= value (help).
↑ Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riesmeyer JS, Riddle MC, Rydén L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I, Cushman WC, Franek E, Hancu N, Hanefeld M, Holt S, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Cardona Munoz EG, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T (July 2019). "Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial". Lancet. 394 (10193): 121–130. doi:10.1016/S0140-6736(19)31149-3. PMID 31189511.
↑ Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB (July 2016). "Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes". N Engl J Med. 375 (4): 311–22. doi:10.1056/NEJMoa1603827. PMC 4985288. PMID 27295427.
↑ Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsbøll T (November 2016). "Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes". N Engl J Med. 375 (19): 1834–1844. doi:10.1056/NEJMoa1607141. PMID 27633186.
↑ McGuire DK, Marx N, Mulvagh SL, Deanfield JE, Inzucchi SE, Pop-Busui R, Mann JF, Emerson SS, Poulter NR, Engelmann MD, Ripa MS, Hovingh GK, Brown-Frandsen K, Bain SC, Cavender MA, Gislum M, David JP, Buse JB (May 2025). "Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes". N Engl J Med. 392 (20): 2001–2012. doi:10.1056/NEJMoa2501006. PMID 40162642 Check |pmid= value (help).
↑ Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JF, Bakris G, Baeres FM, Idorn T, Bosch-Traberg H, Lausvig NL, Pratley R (July 2024). "Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes". N Engl J Med. 391 (2): 109–121. doi:10.1056/NEJMoa2403347. PMID 38785209 Check |pmid= value (help).
↑ Kosiborod MN, Petrie MC, Borlaug BA, Butler J, Davies MJ, Hovingh GK, Kitzman DW, Møller DV, Treppendahl MB, Verma S, Jensen TJ, Liisberg K, Lindegaard ML, Abhayaratna W, Ahmed FZ, Ben-Gal T, Chopra V, Ezekowitz JA, Fu M, Ito H, Lelonek M, Melenovský V, Merkely B, Núñez J, Perna E, Schou M, Senni M, Sharma K, van der Meer P, Von Lewinski D, Wolf D, Shah SJ (April 2024). "Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes". N Engl J Med. 390 (15): 1394–1407. doi:10.1056/NEJMoa2313917. PMID 38587233 Check |pmid= value (help).
↑ Butler J, Shah SJ, Petrie MC, Borlaug BA, Abildstrøm SZ, Davies MJ, Hovingh GK, Kitzman DW, Møller DV, Verma S, Einfeldt MN, Lindegaard ML, Rasmussen S, Abhayaratna W, Ahmed FZ, Ben-Gal T, Chopra V, Ezekowitz JA, Fu M, Ito H, Lelonek M, Melenovský V, Merkely B, Núñez J, Perna E, Schou M, Senni M, Sharma K, van der Meer P, Von Lewinski D, Wolf D, Kosiborod MN (April 2024). "Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials". Lancet. 403 (10437): 1635–1648. doi:10.1016/S0140-6736(24)00469-0. PMC 11317105 Check |pmc= value (help). PMID 38599221 Check |pmid= value (help).
↑ Almandoz JP, Lingvay I, Morales J, Campos C (October 2020). "Switching Between Glucagon-Like Peptide-1 Receptor Agonists: Rationale and Practical Guidance". Clin Diabetes. 38 (4): 390–402. doi:10.2337/cd19-0100. PMC 7566932 Check |pmc= value (help). PMID 33132510 Check |pmid= value (help).
↑ Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K (August 2021). "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes". N Engl J Med. 385 (6): 503–515. doi:10.1056/NEJMoa2107519. PMID 34170647 Check |pmid= value (help).
↑ ^64.0 ^64.1 Holman RR, Haffner SM, McMurray JJ, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamás G, Tognoni G, Tuomilehto J, Villamil AS, Vozár J, Califf RM (April 2010). "Effect of nateglinide on the incidence of diabetes and cardiovascular events". N Engl J Med. 362 (16): 1463–76. doi:10.1056/NEJMoa1001122. PMID 20228402.
↑ Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR (August 2017). "Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes". N Engl J Med. 377 (7): 644–657. doi:10.1056/NEJMoa1611925. PMID 28605608.
↑ Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE (November 2015). "Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes". N Engl J Med. 373 (22): 2117–28. doi:10.1056/NEJMoa1504720. PMID 26378978.
↑ Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJ, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW (June 2019). "Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy". N Engl J Med. 380 (24): 2295–2306. doi:10.1056/NEJMoa1811744. PMID 30990260.
↑ Heerspink HJ, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JF, McMurray JJ, Lindberg M, Rossing P, Sjöström CD, Toto RD, Langkilde AM, Wheeler DC (October 2020). "Dapagliflozin in Patients with Chronic Kidney Disease". N Engl J Med. 383 (15): 1436–1446. doi:10.1056/NEJMoa2024816. PMID 32970396 Check |pmid= value (help).
↑ Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SY, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R (January 2023). "Empagliflozin in Patients with Chronic Kidney Disease". N Engl J Med. 388 (2): 117–127. doi:10.1056/NEJMoa2204233. PMC 7614055 Check |pmc= value (help). PMID 36331190 Check |pmid= value (help).
↑ McMurray JJ, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CE, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM (November 2019). "Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction". N Engl J Med. 381 (21): 1995–2008. doi:10.1056/NEJMoa1911303. PMID 31535829.
↑ Solomon SD, McMurray JJ, Claggett B, de Boer RA, DeMets D, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CS, Martinez F, Shah SJ, Desai AS, Jhund PS, Belohlavek J, Chiang CE, Borleffs CJ, Comin-Colet J, Dobreanu D, Drozdz J, Fang JC, Alcocer-Gamba MA, Al Habeeb W, Han Y, Cabrera Honorio JW, Janssens SP, Katova T, Kitakaze M, Merkely B, O'Meara E, Saraiva JF, Tereshchenko SN, Thierer J, Vaduganathan M, Vardeny O, Verma S, Pham VN, Wilderäng U, Zaozerska N, Bachus E, Lindholm D, Petersson M, Langkilde AM (September 2022). "Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction". N Engl J Med. 387 (12): 1089–1098. doi:10.1056/NEJMoa2206286. PMID 36027570 Check |pmid= value (help).
↑ Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Silverman MG, Zelniker TA, Kuder JF, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JP, Ruff CT, Gause-Nilsson IA, Fredriksson M, Johansson PA, Langkilde AM, Sabatine MS (January 2019). "Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes". N Engl J Med. 380 (4): 347–357. doi:10.1056/NEJMoa1812389. PMID 30415602.
↑ Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F (October 2020). "Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure". N Engl J Med. 383 (15): 1413–1424. doi:10.1056/NEJMoa2022190. PMID 32865377 Check |pmid= value (help).
↑ Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Piña IL, Ponikowski P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Carson P, Lam CS, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M (October 2021). "Empagliflozin in Heart Failure with a Preserved Ejection Fraction". N Engl J Med. 385 (16): 1451–1461. doi:10.1056/NEJMoa2107038. PMID 34449189 Check |pmid= value (help).
↑ Rosenstock J, Kahn SE, Johansen OE, Zinman B, Espeland MA, Woerle HJ, Pfarr E, Keller A, Mattheus M, Baanstra D, Meinicke T, George JT, von Eynatten M, McGuire DK, Marx N (September 2019). "Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial". JAMA. 322 (12): 1155–1166. doi:10.1001/jama.2019.13772. PMC 6763993 Check |pmc= value (help). PMID 31536101.
↑ Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefèbvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Korányi L, Laakso M, Mokán M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J (October 2005). "Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial". Lancet. 366 (9493): 1279–89. doi:10.1016/S0140-6736(05)67528-9. PMID 16214598.
↑ Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, Brass LM, Schwartz GG, Adams HP, Berger L, Carolei A, Clark W, Coull B, Ford GA, Kleindorfer D, O'Leary JR, Parsons MW, Ringleb P, Sen S, Spence JD, Tanne D, Wang D, Winder TR (April 2016). "Pioglitazone after Ischemic Stroke or Transient Ischemic Attack". N Engl J Med. 374 (14): 1321–31. doi:10.1056/NEJMoa1506930. PMC 4887756. PMID 26886418.
↑ Spence JD, Viscoli C, Kernan WN, Young LH, Furie K, DeFronzo R, Abdul-Ghani M, Dandona P, Inzucchi SE (June 2022). "Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance". Diabetes Obes Metab. 24 (6): 1150–1158. doi:10.1111/dom.14687. PMID 35253334 Check |pmid= value (help).
↑ ^79.0 ^79.1 ^79.2 "Introduction and Methodology: Standards of Care in Diabetes-2025". Diabetes Care. 48 (1 Suppl 1): S1–S5. January 2025. doi:10.2337/dc25-SINT. PMID 39651982 Check |pmid= value (help).
↑ Avgerinos I, Karagiannis T, Kakotrichi P, Michailidis T, Liakos A, Matthews DR, Tsapas A, Bekiari E (January 2022). "Sotagliflozin for patients with type 2 diabetes: A systematic review and meta-analysis". Diabetes Obes Metab. 24 (1): 106–114. doi:10.1111/dom.14555. PMID 34545668 Check |pmid= value (help).
↑ "Practical Insulin: A Handbook for Prescribing Providers | Books Gateway | American Diabetes Association".
↑ Gerstein HC, Bosch J, Dagenais GR, Díaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Rydén LE, Yusuf S (July 2012). "Basal insulin and cardiovascular and other outcomes in dysglycemia". N Engl J Med. 367 (4): 319–28. doi:10.1056/NEJMoa1203858. PMID 22686416.
↑ Lean MEJ, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamson AJ, Sniehotta FF, Mathers JC, Ross HM, McIlvenna Y, Stefanetti R, Trenell M, Welsh P, Kean S, Ford I, McConnachie A, Sattar N, Taylor R. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018;391(10120):541-551. doi:10.1016/S0140-6736(17)33102-1.
↑ LeRoith D, Biessels GJ, Braithwaite SS, Casanueva FF, Draznin B, Halter JB, Hirsch IB, McDonnell ME, Molitch ME, Murad MH, Sinclair AJ (May 2019). "Treatment of Diabetes in Older Adults: An Endocrine Society* Clinical Practice Guideline". J Clin Endocrinol Metab. 104 (5): 1520–1574. doi:10.1210/jc.2019-00198. PMC 7271968 Check |pmc= value (help).
↑ Qaseem A, Wilt TJ, Kansagara D, Horwitch C, Barry MJ, Forciea MA, Fitterman N, Balzer K, Boyd C, Humphrey LL, Iorio A, Lin J, Maroto M, McLean R, Mustafa R, Tufte J (April 2018). "Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians". Ann Intern Med. 168 (8): 569–576. doi:10.7326/M17-0939. PMID 29507945.
↑ Qaseem A, Obley AJ, Shamliyan T, Hicks LA, Harrod CS, Crandall CJ, Balk EM, Cooney TG, Cross JT, Fitterman N, Lin JS, Maroto M, Miller MC, Shekelle P, Tice JA, Tufte JE, Etxeandia-Ikobaltzeta I, Yost J (May 2024). "Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians". Ann Intern Med. 177 (5): 658–666. doi:10.7326/M23-2788. PMC 11614146 Check |pmc= value (help). PMID 38639546 Check |pmid= value (help).
↑ Department of Veterans Affairs; Department of Defense. VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus (Version 5.0, April 2017). Washington (DC): VA & DoD; 2017. Available from: https://www.healthquality.va.gov/guidelines/CD/diabetes/VADoD-Diabetes-CPG_Final_508.pdf
↑ Diabetes Canada | Clinical Practice Guidelines
↑ Overview | Type 2 diabetes in adults: management | Guidance | NICE
↑ Roglic G, Norris SL (September 2018). "Medicines for Treatment Intensification in Type 2 Diabetes and Type of Insulin in Type 1 and Type 2 Diabetes in Low-Resource Settings: Synopsis of the World Health Organization Guidelines on Second- and Third-Line Medicines and Type of Insulin for the Control of Blood Glucose Levels in Nonpregnant Adults With Diabetes Mellitus". Ann Intern Med. 169 (6): 394–397. doi:10.7326/M18-1149. PMID 30178023.
↑ Ceriello A, Colagiuri S (April 2025). "IDF global clinical practice recommendations for managing type 2 diabetes - 2025". Diabetes Res Clin Pract. 222 Suppl 1: 112152. doi:10.1016/j.diabres.2025.112152.

[pmid37024129-1] Shi Q, Nong K, Vandvik PO, Guyatt GH, Schnell O, Rydén L; et al. (2023). "Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials". BMJ. 381: e074068. doi:10.1136/bmj-2022-074068. PMC 10077111 Check |pmc= value (help). PMID 37024129 Check |pmid= value (help).

[pmid24145991-2] Qaseem A, Hopkins RH, Sweet DE, Starkey M, Shekelle P (2013). "Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: A clinical practice guideline from the American College of Physicians". Ann. Intern. Med. 159 (12): 835–47. doi:10.7326/0003-4819-159-12-201312170-00726. PMID 24145991.

[pmid27979887-3] "Standards of Medical Care in Diabetes-2017: Summary of Revisions". Diabetes Care. 40 (Suppl 1): S4–S5. 2017. doi:10.2337/dc17-S003. PMID 27979887.

[pmid12145243-4] Colagiuri S, Cull CA, Holman RR (2002). "Are lower fasting plasma glucose levels at diagnosis of type 2 diabetes associated with improved outcomes?: U.K. prospective diabetes study 61". Diabetes Care. 25 (8): 1410–7. PMID 12145243.

[pmid1441492-5] Davidson MB (1992). "Successful treatment of markedly symptomatic patients with type II diabetes mellitus using high doses of sulfonylurea agents". West. J. Med. 157 (2): 199–200. PMC 1011263. PMID 1441492.

[pmid27088241-6] 6.0 ^6.1 Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, Chu Y, Iyoha E, Segal JB, Bolen S (2016). "Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis". Ann. Intern. Med. 164 (11): 740–51. doi:10.7326/M15-2650. PMID 27088241.

[pmid27434443-7] Palmer SC, Mavridis D, Nicolucci A, Johnson DW, Tonelli M, Craig JC, Maggo J, Gray V, De Berardis G, Ruospo M, Natale P, Saglimbene V, Badve SV, Cho Y, Nadeau-Fredette AC, Burke M, Faruque L, Lloyd A, Ahmad N, Liu Y, Tiv S, Wiebe N, Strippoli GF (2016). "Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis". JAMA. 316 (3): 313–24. doi:10.1001/jama.2016.9400. PMID 27434443.

[8] GitHub Contributors. Hypertonic Saline for Bronchiolitis: a living systematic review. GitHub. Available at http://openmetaanalysis.github.io/Diabetes-mellitus-type-2-mortality-prevention-with-pharmacotherapy/. Accessed June 11, 2018.

[pmid31372016-9] Mesinovic J, Zengin A, De Courten B, Ebeling PR, Scott D (2019). "Sarcopenia and type 2 diabetes mellitus: a bidirectional relationship". Diabetes Metab Syndr Obes. 12: 1057–1072. doi:10.2147/DMSO.S186600. PMC 6630094 Check |pmc= value (help). PMID 31372016.

[EurichWeir2013-10] Eurich, Dean T.; Weir, Daniala L.; Majumdar, Sumit R.; Tsuyuki, Ross T.; Johnson, Jeffrey A.; Tjosvold, Lisa; Vanderloo, Saskia E.; McAlister, Finlay A. (2013). "Comparative Safety and Effectiveness of Metformin in Patients With Diabetes Mellitus and Heart Failure". Circulation: Heart Failure. 6 (3): 395–402. doi:10.1161/CIRCHEARTFAILURE.112.000162. ISSN 1941-3289.

[pmid30761687-11] Mendy A, Gopal R, Alcorn JF, Forno E (2019). "Reduced mortality from lower respiratory tract disease in adult diabetic patients treated with metformin". Respirology. 24 (7): 646–651. doi:10.1111/resp.13486. PMC 6579707 Check |pmc= value (help). PMID 30761687.

[LiangDing2019-12] Liang, Huoyan; Ding, Xianfei; Li, Lifeng; Wang, Tian; Kan, Quancheng; Wang, Lexin; Sun, Tongwen (2019). "Association of preadmission metformin use and mortality in patients with sepsis and diabetes mellitus: a systematic review and meta-analysis of cohort studies". Critical Care. 23 (1). doi:10.1186/s13054-019-2346-4. ISSN 1364-8535.

[SinghKhunti2020-13] Singh, Awadhesh Kumar; Khunti, Kamlesh (2020). "Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review". Diabetes Research and Clinical Practice. 165: 108266. doi:10.1016/j.diabres.2020.108266. ISSN 0168-8227.

[WuZhou2020-14] Wu, Yingjie; Zhou, An; Tang, Li; Lei, Yuanyuan; Tang, Bo; Zhang, Linjing (2020). "Bile Acids: Key Regulators and Novel Treatment Targets for Type 2 Diabetes". Journal of Diabetes Research. 2020: 1–11. doi:10.1155/2020/6138438. ISSN 2314-6745.

[pmid9167101-15] Sulkin TV, Bosman D, Krentz AJ (1997). "Contraindications to metformin therapy in patients with NIDDM". Diabetes Care. 20 (6): 925–8. doi:10.2337/diacare.20.6.925. PMID 9167101.

[pmid16283245-16] Holstein A, Stumvoll M (2005). "Contraindications can damage your health--is metformin a case in point?". Diabetologia. 48 (12): 2454–9. doi:10.1007/s00125-005-0026-1. PMID 16283245.

[pmid9428832-17] Garber AJ, Duncan TG, Goodman AM, Mills DJ, Rohlf JL (1997). "Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose-response trial". Am J Med. 103 (6): 491–7. doi:10.1016/s0002-9343(97)00254-4. PMID 9428832.

[pmid30508012-18] Herkert D, Vijayakumar P, Luo J, Schwartz JI, Rabin TL, DeFilippo E; et al. (2018). "Cost-Related Insulin Underuse Among Patients With Diabetes". JAMA Intern Med. doi:10.1001/jamainternmed.2018.5008. PMID 30508012.

[pmid25785977-19] Greene JA, Riggs KR (2015). "Why is there no generic insulin? Historical origins of a modern problem". N Engl J Med. 372 (12): 1171–5. doi:10.1056/NEJMms1411398. PMID 25785977.

[pmid30694321-20] Luo J, Khan NF, Manetti T, Rose J, Kaloghlian A, Gadhe B; et al. (2019). "Implementation of a Health Plan Program for Switching From Analogue to Human Insulin and Glycemic Control Among Medicare Beneficiaries With Type 2 Diabetes". JAMA. 321 (4): 374–384. doi:10.1001/jama.2018.21364. PMID 30694321.

[pmid29936529-21] 21.0 ^21.1 ^21.2 Lipska KJ, Parker MM, Moffet HH, Huang ES, Karter AJ (2018). "Association of Initiation of Basal Insulin Analogs vs Neutral Protamine Hagedorn Insulin With Hypoglycemia-Related Emergency Department Visits or Hospital Admissions and With Glycemic Control in Patients With Type 2 Diabetes". JAMA. 320 (1): 53–62. doi:10.1001/jama.2018.7993. PMC 6134432. PMID 29936529.

[pmid17443605-22] 22.0 ^22.1 Horvath K, Jeitler K, Berghold A, Ebrahim SH, Gratzer TW, Plank J; et al. (2007). "Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus". Cochrane Database Syst Rev (2): CD005613. doi:10.1002/14651858.CD005613.pub3. PMID 17443605. Review in: ACP J Club. 2007 Sep-Oct;147(2):46

[pmid313720162-23] Mesinovic J, Zengin A, De Courten B, Ebeling PR, Scott D (2019). "Sarcopenia and type 2 diabetes mellitus: a bidirectional relationship". Diabetes Metab Syndr Obes. 12: 1057–1072. doi:10.2147/DMSO.S186600. PMC 6630094 Check |pmc= value (help). PMID 31372016.

[pmid18936501-24] Esposito K; et al. (2008). "Addition of neutral protamine lispro insulin or insulin glargine to oral type 2 diabetes regimens for patients with suboptimal glycemic control: a randomized trial". Ann Intern Med. 149: 531–9. PMID 18936501.

[pmid17890232-25] Holman RR; et al. (2007). "Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes". N Engl J Med. 357: 1716–30. doi:10.1056/NEJMoa075392. PMID 17890232.

[pmid18794553-26] Qayyum R, Bolen S, Maruthur N, Feldman L, Wilson LM, Marinopoulos SS; et al. (2008). "Systematic review: comparative effectiveness and safety of premixed insulin analogues in type 2 diabetes". Ann Intern Med. 149 (8): 549–59. PMC 4762020. PMID 18794553.

[pmid1406860-27] 27.0 ^27.1 ^27.2 Yki-Järvinen H, Kauppila M, Kujansuu E; et al. (1992). "Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus". N. Engl. J. Med. 327 (20): 1426–33. PMID 1406860.

[pmid10068412-28] 28.0 ^28.1 ^28.2 Yki-Järvinen H, Ryysy L, Nikkilä K, Tulokas T, Vanamo R, Heikkilä M (1999). "Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial". Ann. Intern. Med. 130 (5): 389–96. PMID 10068412.

[pmid33166419-29] Semlitsch T, Engler J, Siebenhofer A, Jeitler K, Berghold A, Horvath K (2020). "(Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus". Cochrane Database Syst Rev. 11: CD005613. doi:10.1002/14651858.CD005613.pub4. PMC 8095010 Check |pmc= value (help). PMID 33166419 Check |pmid= value (help).

[pmid9761809-30] Kratz A, Lewandrowski KB (1998). "Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Normal reference laboratory values". N. Engl. J. Med. 339 (15): 1063–72. PMID 9761809.

[pmid30851006-31] Russell-Jones D, Dauchy A, Delgado E, Dimitriadis G, Frandsen HA, Popescu L; et al. (2019). "Take Control: A randomized trial evaluating the efficacy and safety of self- versus physician-managed titration of insulin glargine 300 U/mL in patients with uncontrolled type 2 diabetes". Diabetes Obes Metab. 21 (7): 1615–1624. doi:10.1111/dom.13697. PMC 6767413 Check |pmc= value (help). PMID 30851006.

[32] Novo Nordisk has partnerships to provide low-cost human insulin. Available at https://www.novocare.com/diabetes-overview/let-us-help/human-insulin-options.html

[pmid10755495-33] Fonseca V, Rosenstock J, Patwardhan R, Salzman A (2000). "Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial". JAMA. 283 (13): 1695–702. doi:10.1001/jama.283.13.1695. PMID 10755495.

[SinghKhunti20202-34] Singh, Awadhesh Kumar; Khunti, Kamlesh (2020). "Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review". Diabetes Research and Clinical Practice. 165: 108266. doi:10.1016/j.diabres.2020.108266. ISSN 0168-8227.

[ZelnikerWiviott2019-35] 35.0 ^35.1 Zelniker, Thomas A.; Wiviott, Stephen D.; Raz, Itamar; Im, KyungAh; Goodrich, Erica L.; Furtado, Remo H.M.; Bonaca, Marc P.; Mosenzon, Ofri; Kato, Eri T.; Cahn, Avivit; Bhatt, Deepak L.; Leiter, Lawrence A.; McGuire, Darren K.; Wilding, John P.H.; Sabatine, Marc S. (2019). "Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus". Circulation. 139 (17): 2022–2031. doi:10.1161/CIRCULATIONAHA.118.038868. ISSN 0009-7322.

[PalmerTendal2021-36] Palmer, Suetonia C; Tendal, Britta; Mustafa, Reem A; Vandvik, Per Olav; Li, Sheyu; Hao, Qiukui; Tunnicliffe, David; Ruospo, Marinella; Natale, Patrizia; Saglimbene, Valeria; Nicolucci, Antonio; Johnson, David W; Tonelli, Marcello; Rossi, Maria Chiara; Badve, Sunil V; Cho, Yeoungjee; Nadeau-Fredette, Annie-Claire; Burke, Michael; Faruque, Labib I; Lloyd, Anita; Ahmad, Nasreen; Liu, Yuanchen; Tiv, Sophanny; Millard, Tanya; Gagliardi, Lucia; Kolanu, Nithin; Barmanray, Rahul D; McMorrow, Rita; Raygoza Cortez, Ana Karina; White, Heath; Chen, Xiangyang; Zhou, Xu; Liu, Jiali; Rodríguez, Andrea Flores; González-Colmenero, Alejandro Díaz; Wang, Yang; Li, Ling; Sutanto, Surya; Solis, Ricardo Cesar; Díaz González-Colmenero, Fernando; Rodriguez-Gutierrez, René; Walsh, Michael; Guyatt, Gordon; Strippoli, Giovanni F M (2021). "Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials". BMJ: m4573. doi:10.1136/bmj.m4573. ISSN 1756-1833.

[pmid28606340-37] 37.0 ^37.1 Paneni F, Lüscher TF (2017). "Cardiovascular Protection in the Treatment of Type 2 Diabetes: A Review of Clinical Trial Results Across Drug Classes". Am J Cardiol. 120 (1S): S17–S27. doi:10.1016/j.amjcard.2017.05.015. PMID 28606340.

[VermaMazer2019-38] Verma, Subodh; Mazer, C. David; Yan, Andrew T.; Mason, Tamique; Garg, Vinay; Teoh, Hwee; Zuo, Fei; Quan, Adrian; Farkouh, Michael E.; Fitchett, David H.; Goodman, Shaun G.; Goldenberg, Ronald M.; Al-Omran, Mohammed; Gilbert, Richard E.; Bhatt, Deepak L.; Leiter, Lawrence A.; Jüni, Peter; Zinman, Bernard; Connelly, Kim A. (2019). "Effect of Empagliflozin on Left Ventricular Mass in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease". Circulation. 140 (21): 1693–1702. doi:10.1161/CIRCULATIONAHA.119.042375. ISSN 0009-7322.

[FurtadoBonaca2019-39] Furtado, Remo H.M.; Bonaca, Marc P.; Raz, Itamar; Zelniker, Thomas A.; Mosenzon, Ofri; Cahn, Avivit; Kuder, Julia; Murphy, Sabina A.; Bhatt, Deepak L.; Leiter, Lawrence A.; McGuire, Darren K.; Wilding, John P.H.; Ruff, Christian T.; Nicolau, Jose C.; Gause-Nilsson, Ingrid A.M.; Fredriksson, Martin; Langkilde, Anna Maria; Sabatine, Marc S.; Wiviott, Stephen D. (2019). "Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction". Circulation. 139 (22): 2516–2527. doi:10.1161/CIRCULATIONAHA.119.039996. ISSN 0009-7322.

[EickhoffOlsen2020-40] Eickhoff, Mie K.; Olsen, Flemming J.; Frimodt-Møller, Marie; Diaz, Lars J.; Faber, Jens; Jensen, Magnus T.; Rossing, Peter; Persson, Frederik (2020). "Effect of dapagliflozin on cardiac function in people with type 2 diabetes and albuminuria – A double blind randomized placebo-controlled crossover trial". Journal of Diabetes and its Complications. 34 (7): 107590. doi:10.1016/j.jdiacomp.2020.107590. ISSN 1056-8727.

[NakhlehZloczower2020-41] Nakhleh, Afif; Zloczower, Moshe; Gabay, Linoy; Shehadeh, Naim (2020). "Effects of sodium glucose co-transporter 2 inhibitors on genital infections in female patients with type 2 diabetes mellitus– Real world data analysis". Journal of Diabetes and its Complications. 34 (7): 107587. doi:10.1016/j.jdiacomp.2020.107587. ISSN 1056-8727.

[Diagnosis_and_Treatment_of_Type_2_Diabetes_in_Adults-42] 42.0 ^42.1 ^42.2 Kalyani RR, Neumiller JJ, Maruthur NM, Wexler DJ (September 2025). "Diagnosis and Treatment of Type 2 Diabetes in Adults: A Review". JAMA. 334 (11): 984–1002. doi:10.1001/jama.2025.5956. PMID 40549398 Check |pmid= value (help).

[Comparative_Effectiveness_of_Glucose-Lowering_Drugs_for_Type_2_Diabetes-43] Tsapas A, Avgerinos I, Karagiannis T, Malandris K, Manolopoulos A, Andreadis P, Liakos A, Matthews DR, Bekiari E (August 2020). "Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis". Ann Intern Med. 173 (4): 278–286. doi:10.7326/M20-0864. PMID 32598218 Check |pmid= value (help).

[Management_of_type_2_diabetes_with_the_dual_GIP/GLP-1_receptor_agonist_tirzepatide-44] 44.0 ^44.1 Karagiannis T, Avgerinos I, Liakos A, Del Prato S, Matthews DR, Tsapas A, Bekiari E (August 2022). "Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis". Diabetologia. 65 (8): 1251–1261. doi:10.1007/s00125-022-05715-4. PMC 9112245 Check |pmc= value (help). PMID 35579691 Check |pmid= value (help).

[Comparative_efficacy_of_glucose-lowering_medications_on_body_weight_and_blood_pressure_in_patients_with_type_2_diabetes-45] Tsapas A, Karagiannis T, Kakotrichi P, Avgerinos I, Mantsiou C, Tousinas G, Manolopoulos A, Liakos A, Malandris K, Matthews DR, Bekiari E (September 2021). "Comparative efficacy of glucose-lowering medications on body weight and blood pressure in patients with type 2 diabetes: A systematic review and network meta-analysis". Diabetes Obes Metab. 23 (9): 2116–2124. doi:10.1111/dom.14451. PMID 34047443 Check |pmid= value (help).

[urlCMS_Medicaid_Data-46] 46.0 ^46.1 "CMS Medicaid Data".

[urlMicromedex_Products:_Please_Login-47] 47.0 ^47.1 ^47.2 ^47.3 "Micromedex Products: Please Login".

[Diagnosis_and_Management_of_Prediabetes-48] Echouffo-Tcheugui JB, Perreault L, Ji L, Dagogo-Jack S (April 2023). "Diagnosis and Management of Prediabetes: A Review". JAMA. 329 (14): 1206–1216. doi:10.1001/jama.2023.4063. PMID 37039787 Check |pmid= value (help).

[Beta-cell_failure_in_type_2_diabetes-49] Wysham C, Shubrook J (November 2020). "Beta-cell failure in type 2 diabetes: mechanisms, markers, and clinical implications". Postgrad Med. 132 (8): 676–686. doi:10.1080/00325481.2020.1771047. PMID 32543261 Check |pmid= value (help).

[Effects_of_acarbose_on_cardiovascular_and_diabetes_outcomes-50] Holman RR, Coleman RL, Chan JC, Chiasson JL, Feng H, Ge J, Gerstein HC, Gray R, Huo Y, Lang Z, McMurray JJ, Rydén L, Schröder S, Sun Y, Theodorakis MJ, Tendera M, Tucker L, Tuomilehto J, Wei Y, Yang W, Wang D, Hu D, Pan C (November 2017). "Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial". Lancet Diabetes Endocrinol. 5 (11): 877–886. doi:10.1016/S2213-8587(17)30309-1. PMID 28917545.

[intensive_glycaemic_control_in_type_2_diabetes_extended_from_10_years_to_24_years-51] Adler AI, Coleman RL, Leal J, Whiteley WN, Clarke P, Holman RR (July 2024). "Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91)". Lancet. 404 (10448): 145–155. doi:10.1016/S0140-6736(24)00537-3. PMID 38772405 Check |pmid= value (help).

[10-year_follow-up_of_intensive_glucose_control-52] Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA (October 2008). "10-year follow-up of intensive glucose control in type 2 diabetes". N Engl J Med. 359 (15): 1577–89. doi:10.1056/NEJMoa0806470. PMID 18784090.

[Saxagliptin_and_cardiovascular_outcomes-53] Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I (October 2013). "Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus". N Engl J Med. 369 (14): 1317–26. doi:10.1056/NEJMoa1307684. PMID 23992601.

[Tirzepatide_for_Heart_Failure-54] Packer M, Zile MR, Kramer CM, Baum SJ, Litwin SE, Menon V, Ge J, Weerakkody GJ, Ou Y, Bunck MC, Hurt KC, Murakami M, Borlaug BA (January 2025). "Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity". N Engl J Med. 392 (5): 427–437. doi:10.1056/NEJMoa2410027. PMID 39555826 Check |pmid= value (help).

[REWIND-55] Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riesmeyer JS, Riddle MC, Rydén L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I, Cushman WC, Franek E, Hancu N, Hanefeld M, Holt S, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Cardona Munoz EG, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T (July 2019). "Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial". Lancet. 394 (10193): 121–130. doi:10.1016/S0140-6736(19)31149-3. PMID 31189511.

[Liraglutide_and_Cardiovascular_Outcomes-56] Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB (July 2016). "Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes". N Engl J Med. 375 (4): 311–22. doi:10.1056/NEJMoa1603827. PMC 4985288. PMID 27295427.

[Semaglutide_and_Cardiovascular_Outcomes-57] Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsbøll T (November 2016). "Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes". N Engl J Med. 375 (19): 1834–1844. doi:10.1056/NEJMoa1607141. PMID 27633186.

[Oral_Semaglutide_and_Cardiovascular_Outcomes-58] McGuire DK, Marx N, Mulvagh SL, Deanfield JE, Inzucchi SE, Pop-Busui R, Mann JF, Emerson SS, Poulter NR, Engelmann MD, Ripa MS, Hovingh GK, Brown-Frandsen K, Bain SC, Cavender MA, Gislum M, David JP, Buse JB (May 2025). "Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes". N Engl J Med. 392 (20): 2001–2012. doi:10.1056/NEJMoa2501006. PMID 40162642 Check |pmid= value (help).

[Effects_of_Semaglutide_on_Chronic_Kidney_Disease-59] Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JF, Bakris G, Baeres FM, Idorn T, Bosch-Traberg H, Lausvig NL, Pratley R (July 2024). "Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes". N Engl J Med. 391 (2): 109–121. doi:10.1056/NEJMoa2403347. PMID 38785209 Check |pmid= value (help).

[Semaglutide_in_Patients_with_Obesity-Related_Heart_Failure-60] Kosiborod MN, Petrie MC, Borlaug BA, Butler J, Davies MJ, Hovingh GK, Kitzman DW, Møller DV, Treppendahl MB, Verma S, Jensen TJ, Liisberg K, Lindegaard ML, Abhayaratna W, Ahmed FZ, Ben-Gal T, Chopra V, Ezekowitz JA, Fu M, Ito H, Lelonek M, Melenovský V, Merkely B, Núñez J, Perna E, Schou M, Senni M, Sharma K, van der Meer P, Von Lewinski D, Wolf D, Shah SJ (April 2024). "Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes". N Engl J Med. 390 (15): 1394–1407. doi:10.1056/NEJMoa2313917. PMID 38587233 Check |pmid= value (help).

[Semaglutide_versus_placebo-61] Butler J, Shah SJ, Petrie MC, Borlaug BA, Abildstrøm SZ, Davies MJ, Hovingh GK, Kitzman DW, Møller DV, Verma S, Einfeldt MN, Lindegaard ML, Rasmussen S, Abhayaratna W, Ahmed FZ, Ben-Gal T, Chopra V, Ezekowitz JA, Fu M, Ito H, Lelonek M, Melenovský V, Merkely B, Núñez J, Perna E, Schou M, Senni M, Sharma K, van der Meer P, Von Lewinski D, Wolf D, Kosiborod MN (April 2024). "Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials". Lancet. 403 (10437): 1635–1648. doi:10.1016/S0140-6736(24)00469-0. PMC 11317105 Check |pmc= value (help). PMID 38599221 Check |pmid= value (help).

[Switching_Between_Glucagon-Like_Peptide-1_Receptor_Agonists-62] Almandoz JP, Lingvay I, Morales J, Campos C (October 2020). "Switching Between Glucagon-Like Peptide-1 Receptor Agonists: Rationale and Practical Guidance". Clin Diabetes. 38 (4): 390–402. doi:10.2337/cd19-0100. PMC 7566932 Check |pmc= value (help). PMID 33132510 Check |pmid= value (help).

[Tirzepatide_versus_Semaglutide-63] Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K (August 2021). "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes". N Engl J Med. 385 (6): 503–515. doi:10.1056/NEJMoa2107519. PMID 34170647 Check |pmid= value (help).

[Effect_of_nateglinide_on_the_incidence_of_diabetes_and_cardiovascular_events-64] 64.0 ^64.1 Holman RR, Haffner SM, McMurray JJ, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamás G, Tognoni G, Tuomilehto J, Villamil AS, Vozár J, Califf RM (April 2010). "Effect of nateglinide on the incidence of diabetes and cardiovascular events". N Engl J Med. 362 (16): 1463–76. doi:10.1056/NEJMoa1001122. PMID 20228402.

[Canagliflozin_and_Cardiovascular_and_Renal_Events-65] Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR (August 2017). "Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes". N Engl J Med. 377 (7): 644–657. doi:10.1056/NEJMoa1611925. PMID 28605608.

[Empagliflozin,_Cardiovascular_Outcomes,_and_Mortality-66] Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE (November 2015). "Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes". N Engl J Med. 373 (22): 2117–28. doi:10.1056/NEJMoa1504720. PMID 26378978.

[Canagliflozin_and_Renal_Outcomes-67] Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJ, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW (June 2019). "Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy". N Engl J Med. 380 (24): 2295–2306. doi:10.1056/NEJMoa1811744. PMID 30990260.

[Dapagliflozin_in_Patients_with_Chronic_Kidney_Disease-68] Heerspink HJ, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JF, McMurray JJ, Lindberg M, Rossing P, Sjöström CD, Toto RD, Langkilde AM, Wheeler DC (October 2020). "Dapagliflozin in Patients with Chronic Kidney Disease". N Engl J Med. 383 (15): 1436–1446. doi:10.1056/NEJMoa2024816. PMID 32970396 Check |pmid= value (help).

[Empagliflozin_in_Patients_with_Chronic_Kidney_Disease-69] Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SY, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R (January 2023). "Empagliflozin in Patients with Chronic Kidney Disease". N Engl J Med. 388 (2): 117–127. doi:10.1056/NEJMoa2204233. PMC 7614055 Check |pmc= value (help). PMID 36331190 Check |pmid= value (help).

[Dapagliflozin_in_Patients_with_Heart_Failure-70] McMurray JJ, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CE, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM (November 2019). "Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction". N Engl J Med. 381 (21): 1995–2008. doi:10.1056/NEJMoa1911303. PMID 31535829.

[Dapagliflozin_in_Heart_Failure_with_Mildly_Reduced_or_Preserved_Ejection_Fraction-71] Solomon SD, McMurray JJ, Claggett B, de Boer RA, DeMets D, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CS, Martinez F, Shah SJ, Desai AS, Jhund PS, Belohlavek J, Chiang CE, Borleffs CJ, Comin-Colet J, Dobreanu D, Drozdz J, Fang JC, Alcocer-Gamba MA, Al Habeeb W, Han Y, Cabrera Honorio JW, Janssens SP, Katova T, Kitakaze M, Merkely B, O'Meara E, Saraiva JF, Tereshchenko SN, Thierer J, Vaduganathan M, Vardeny O, Verma S, Pham VN, Wilderäng U, Zaozerska N, Bachus E, Lindholm D, Petersson M, Langkilde AM (September 2022). "Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction". N Engl J Med. 387 (12): 1089–1098. doi:10.1056/NEJMoa2206286. PMID 36027570 Check |pmid= value (help).

[Dapagliflozin_and_Cardiovascular_Outcomes_in_Type_2_Diabetes-72] Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Silverman MG, Zelniker TA, Kuder JF, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JP, Ruff CT, Gause-Nilsson IA, Fredriksson M, Johansson PA, Langkilde AM, Sabatine MS (January 2019). "Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes". N Engl J Med. 380 (4): 347–357. doi:10.1056/NEJMoa1812389. PMID 30415602.

[Cardiovascular_and_Renal_Outcomes_with_Empagliflozin_in_Heart_Failure-73] Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F (October 2020). "Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure". N Engl J Med. 383 (15): 1413–1424. doi:10.1056/NEJMoa2022190. PMID 32865377 Check |pmid= value (help).

[Empagliflozin_in_Heart_Failure_with_a_Preserved_Ejection_Fraction-74] Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Piña IL, Ponikowski P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Carson P, Lam CS, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M (October 2021). "Empagliflozin in Heart Failure with a Preserved Ejection Fraction". N Engl J Med. 385 (16): 1451–1461. doi:10.1056/NEJMoa2107038. PMID 34449189 Check |pmid= value (help).

[The_CAROLINA_Randomized_Clinical_Trial-75] Rosenstock J, Kahn SE, Johansen OE, Zinman B, Espeland MA, Woerle HJ, Pfarr E, Keller A, Mattheus M, Baanstra D, Meinicke T, George JT, von Eynatten M, McGuire DK, Marx N (September 2019). "Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial". JAMA. 322 (12): 1155–1166. doi:10.1001/jama.2019.13772. PMC 6763993 Check |pmc= value (help). PMID 31536101.

[PROactive-76] Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefèbvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Korányi L, Laakso M, Mokán M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J (October 2005). "Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial". Lancet. 366 (9493): 1279–89. doi:10.1016/S0140-6736(05)67528-9. PMID 16214598.

[Pioglitazone_after_Ischemic_Stroke-77] Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, Brass LM, Schwartz GG, Adams HP, Berger L, Carolei A, Clark W, Coull B, Ford GA, Kleindorfer D, O'Leary JR, Parsons MW, Ringleb P, Sen S, Spence JD, Tanne D, Wang D, Winder TR (April 2016). "Pioglitazone after Ischemic Stroke or Transient Ischemic Attack". N Engl J Med. 374 (14): 1321–31. doi:10.1056/NEJMoa1506930. PMC 4887756. PMID 26886418.

[Efficacy_of_lower_doses_of_pioglitazone-78] Spence JD, Viscoli C, Kernan WN, Young LH, Furie K, DeFronzo R, Abdul-Ghani M, Dandona P, Inzucchi SE (June 2022). "Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance". Diabetes Obes Metab. 24 (6): 1150–1158. doi:10.1111/dom.14687. PMID 35253334 Check |pmid= value (help).

[Introduction_and_Methodology:_Standards_of_Care_in_Diabetes-2025-79] 79.0 ^79.1 ^79.2 "Introduction and Methodology: Standards of Care in Diabetes-2025". Diabetes Care. 48 (1 Suppl 1): S1–S5. January 2025. doi:10.2337/dc25-SINT. PMID 39651982 Check |pmid= value (help).

[Sotagliflozin_for_patients_with_type_2_diabetes-80] Avgerinos I, Karagiannis T, Kakotrichi P, Michailidis T, Liakos A, Matthews DR, Tsapas A, Bekiari E (January 2022). "Sotagliflozin for patients with type 2 diabetes: A systematic review and meta-analysis". Diabetes Obes Metab. 24 (1): 106–114. doi:10.1111/dom.14555. PMID 34545668 Check |pmid= value (help).

[Practical_Insulin:_A_Handbook_for_Prescribing_Providers_ADA-81] "Practical Insulin: A Handbook for Prescribing Providers | Books Gateway | American Diabetes Association".

[Basal_insulin_and_cardiovascular_and_other_outcomes_in_dysglycemia-82] Gerstein HC, Bosch J, Dagenais GR, Díaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Rydén LE, Yusuf S (July 2012). "Basal insulin and cardiovascular and other outcomes in dysglycemia". N Engl J Med. 367 (4): 319–28. doi:10.1056/NEJMoa1203858. PMID 22686416.

[83] Lean MEJ, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamson AJ, Sniehotta FF, Mathers JC, Ross HM, McIlvenna Y, Stefanetti R, Trenell M, Welsh P, Kean S, Ford I, McConnachie A, Sattar N, Taylor R. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018;391(10120):541-551. doi:10.1016/S0140-6736(17)33102-1.

[Treatment_of_Diabetes_in_Older_Adults-84] LeRoith D, Biessels GJ, Braithwaite SS, Casanueva FF, Draznin B, Halter JB, Hirsch IB, McDonnell ME, Molitch ME, Murad MH, Sinclair AJ (May 2019). "Treatment of Diabetes in Older Adults: An Endocrine Society* Clinical Practice Guideline". J Clin Endocrinol Metab. 104 (5): 1520–1574. doi:10.1210/jc.2019-00198. PMC 7271968 Check |pmc= value (help).

[Hemoglobin_A1c_Targets_for_Glycemic_Control-85] Qaseem A, Wilt TJ, Kansagara D, Horwitch C, Barry MJ, Forciea MA, Fitterman N, Balzer K, Boyd C, Humphrey LL, Iorio A, Lin J, Maroto M, McLean R, Mustafa R, Tufte J (April 2018). "Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians". Ann Intern Med. 168 (8): 569–576. doi:10.7326/M17-0939. PMID 29507945.

[Newer_Pharmacologic_Treatments_in_Adults_With_Type_2_Diabetes-86] Qaseem A, Obley AJ, Shamliyan T, Hicks LA, Harrod CS, Crandall CJ, Balk EM, Cooney TG, Cross JT, Fitterman N, Lin JS, Maroto M, Miller MC, Shekelle P, Tice JA, Tufte JE, Etxeandia-Ikobaltzeta I, Yost J (May 2024). "Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians". Ann Intern Med. 177 (5): 658–666. doi:10.7326/M23-2788. PMC 11614146 Check |pmc= value (help). PMID 38639546 Check |pmid= value (help).

[87] Department of Veterans Affairs; Department of Defense. VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus (Version 5.0, April 2017). Washington (DC): VA & DoD; 2017. Available from: https://www.healthquality.va.gov/guidelines/CD/diabetes/VADoD-Diabetes-CPG_Final_508.pdf

[88] Diabetes Canada | Clinical Practice Guidelines

[89] Overview | Type 2 diabetes in adults: management | Guidance | NICE

[World_Health_Organization_Guidelines-90] Roglic G, Norris SL (September 2018). "Medicines for Treatment Intensification in Type 2 Diabetes and Type of Insulin in Type 1 and Type 2 Diabetes in Low-Resource Settings: Synopsis of the World Health Organization Guidelines on Second- and Third-Line Medicines and Type of Insulin for the Control of Blood Glucose Levels in Nonpregnant Adults With Diabetes Mellitus". Ann Intern Med. 169 (6): 394–397. doi:10.7326/M18-1149. PMID 30178023.

[Diabetes_Res_Clin_Pract-91] Ceriello A, Colagiuri S (April 2025). "IDF global clinical practice recommendations for managing type 2 diabetes - 2025". Diabetes Res Clin Pract. 222 Suppl 1: 112152. doi:10.1016/j.diabres.2025.112152.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

[36]

[37]

[38]

[39]

[40]

[41]

[42]

[43]

[44]

[45]

[46]

[47]

[48]

[49]

[50]

[51]

[52]

[53]

[54]

[55]

[56]

[57]

[58]

[59]

[60]

[61]

[62]

[63]

[64]

[65]

[66]

[67]

[68]

[69]

[70]

[71]

[72]

[73]

[74]

[75]

[76]

[77]

[78]

[79]

[80]

[81]

[82]

[83]

[84]

[85]

[86]

[87]

[88]

[89]

[90]

[91]