Diabetes mellitus type 2 medical therapy
Diabetes mellitus type 2 Microchapters |
Differentiating Diabetes Mellitus Type 2 from other Diseases |
Diagnosis |
Treatment |
Medical therapy |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]
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. 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
Medical therapy starts with metformin monotherapy unless there is a contraindication for it. In the following conditions, treatment starts with dual therapy:[1][2][3][4][5][6]
- 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.[7]
Metformin
Metformin is effective and safe, is inexpensive, and may reduce risk of cardiovascular events and death. Patients should be advised to stop the medication in cases of nausea, vomiting or dehydration. Contraindications to metformin include, heart failure, liver failure, GFR ≤30 and metabolic acidosis.
Insulin
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."[8] More recent randomized controlled trials have found no differences with glargine[9] and have found that although long acting insulins were less effective, they were associated with less hypoglycemia.[10]
Combination therapy
Any agent can be added as second drug based on patient condition but the American Association of Clinical Endocrinologists recommends either incretin based therapy or sodium glucose transporter 2 (SGLT2) inhibition agents.
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 |
|
|
Low |
Sulfonylureas | 2nd generation | Closes K-ATP channels on beta cell plasma membranes | ↑ Insulin secretion |
|
|
Low |
Meglitinides | Closes K-ATP channels on beta cell plasma membranes | ↑ Insulin secretion |
|
|
Moderate | |
Thiazolidinedione
(TZDs) |
Activates the nuclear transcription factor PPAR-gama | ↑ Insulin sensitivity |
|
|
Low | |
α-Glucosidase
inhibitors |
Inhibits intestinal
α-glucosidase |
Slows intestinal carbohydrate
digestion/absorption |
|
|
Low to
moderate | |
DPP-4 | Inhibits DPP-4 activity, increasing postprandial incretin (GLP-1, GIP) concentrations |
|
|
|
High | |
Bile acid sequestrants | Colesevelam | Binds bile acids in intestinal tract,
increasing hepatic bile acid production |
|
|
|
High |
Dopamine-2 | Bromocriptine
(quick release)§ |
Activates dopaminergic receptors |
|
|
|
High |
SGLT2
inhibitors |
Inhibits SGLT2 in the proximal nephron |
|
|
|
High | |
GLP-1 receptor agonists |
|
Activates GLP-1 receptors |
|
|
|
High |
Amylin mimetics | Pramlintide§ | Activates amylin receptors |
|
|
|
High |
Insulins |
|
Activates insulin receptors |
|
|
|
High |
| ||||||
| ||||||
| ||||||
|
‡ lnitial concerns regarding bladder cancer risk are decreasing after subsequent study.
§ Not licensed in Europe for type 2 diabetes.
References
- ↑ 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.
- ↑ 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.
- ↑ Horvath K; et al. (2007). "Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus". Cochrane database of systematic reviews (Online): CD005613. PMID 17443605.
- ↑ 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.
- ↑ 11.0 11.1 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.