Metabolic syndrome medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]

Overview

Metabolic syndrome is formed by a constellation of medical disorders that increases one's risk for cardiovascular disease and diabetes. It effects a large number of people in a clustered fashion. Management of metabolic syndrome involves dietary modifications, exercise and drug therapy for the complications (diabetes, stroke, angina, myocardial infarction) found associated with these conditions.

Treatment

• The first line treatment is change of lifestyle (i.e., caloric restriction, physical activity, weight loss). However, drug treatment is frequently required for complications that are seen with them.

Hypertension

• BP goal- 140/90 or 130/80 in diabetics (JNC 7 guidelines).
• Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) should be preferred over diuretics or beta-blockers in these patients .

Elevated low-density lipoprotein cholesterol (LDL-C)

• The goal is to get the LDL down to < 100 mg/dl.
• Statins are drug of choice.
• Statins are however contraindicated in pregnancy.

Decreased high-density lipoprotein cholesterol (HDL-C)

• Diet (decreased calorie intakes)
• Increased physical activity
• Niacin
• Cholesteryl ester transfer protein (CETP) inhibitors (torcetrapib) and (anacetrapib) are in trial stages and their benefits in increasing HDL levels are yet to be proved.

Elevated Triglyceride

• Fibric acid
• Niacin {however at higher doses (>1500 mg/d) it may exacerbate hyperglycemia}
• Addition of omega-3 fatty acids also produces beneficial effects.

Diabetes

• Use of drugs that decrease insulin resistance e.g., metformin . Use of thiazolidinediones is controversial and not FDA approved.

Cardiovascular risk

• Aspirin therapy may be helpful in the primary prevention of cardiovascular complications.

Trial supportive data

Study on the effects of metformin and life-style changes on the incidence of metabolic syndrome

1) Source & year - Ann Intern Med. 2005

2) Study question – The effect of intensive lifestyle intervention and metformin therapy on the syndrome's incidence and resolution

3) Study design – Randomized controlled trial

4) Study Population – 1711 participants

5) Study period – 3.2 years

6) Interventions - Metformin, 850 mg twice daily, or intensive lifestyle intervention designed to achieve and maintain a 7% weight loss and 150 minutes of exercise per week.

7) Study results –

• 53% of participants (n = 1711) had metabolic syndrome at baseline
• Results of Log-rank test
  • Incidence of the metabolic syndrome was reduced by 41% in the lifestyle group (P < 0.001) and by 17% in the metformin group (P = 0.03) compared with placebo.
  • 3year cumulative incidences were 51%, 45%, and 34% in the placebo, metformin, and lifestyle groups, respectively.

8) Study conclusion - Lifestyle intervention and metformin therapy reduces the development of metabolic syndrome.

The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)

• Source & year - The American Journal of Cardiology

• Study question – Estimate the long-term relative risk of major coronary events (MCEs) associated with the metabolic syndrome

• Study design – Post hoc determination of placebo data from the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) used to estimate the long-term relative risk of major coronary events (MCEs) associated with the metabolic syndrome.
• Study Population –

• Study results – In 4S and AFCAPS/TexCAPS, respectively, Placebo-treated patients with the metabolic syndrome were
  • 1.5 (95% confidence interval 1.2 to 1.8) times more likely to have MCEs than those without it in 4S
  • 1.4 (95% confidence interval 1.04 to 1.9) times more likely to have MCEs than those without it in 4S

• Study conclusion

The following risks factors increased the relative risks for MACE

• • Low high-density lipoprotein levels were associated with elevated risk of MCEs in both studies
  • High triglycerides in 4S
  • Elevated blood pressure and obesity in AFCAPS/TexCAPS were associated with significantly increased relative risk

See also

• Hyperinsulinemia
• Insulin resistance
• Chronic Somogyi rebound