Which patients with metabolic syndrome benefit from metformin?

The effect of metformin and lifestyle change persists at 10 years

A 10-year follow-up study to the Diabetes Prevention Program found that, compared with no intervention, both metformin and lifestyle interventions continued to be associated with a lower incidence of diabetes (no intervention: 7.8 cases per 100 person-years; 95% CI, 4.8-6.5; metformin: 6.4 cases; 95% CI, 4.2-5.7; ARR=1.4% per year; lifestyle interventions: 5.3 cases; 95% CI, 5.1-6.8; ARR=2.5% per year).³

Researchers originally randomized 3234 patients with body mass index ≥24 kg/m², fasting blood sugar 95 to 125 mg/dL, and 2-hour post 75-gm glucose value of 149 to 199 mg/dL to 3 groups: intensive lifestyle modification (weight loss goal of 7%, 150 minutes a week of exercise), metformin (850 mg twice daily), and no inter­vention. After the 2.8-year follow-up period, 2766 patients continued for another 5.7 years of follow-up. Investigators offered group lifestyle counseling to all patients and continued metformin at the same dose in the second group.

Earlier study shows an effect for metformin, but with a caveat

An earlier RCT found that metformin reduced the risk of developing diabetes in patients with metabolic syndrome.⁴ Investigators randomized 70 patients to metformin (250 mg 3 times daily) or placebo for a year. Fewer patients developed diabetes with metformin (3% vs 16.2%, P=.011; NNT=7.6) and more had a normal glucose tolerance test result (84.9% vs 51.4%, P=.011; NNT=3). However, by current American Diabetes Association criteria, half of the subjects had early diabetes at baseline.

Metformin lowers fasting blood sugar, but may not reverse metabolic syndrome

A post-hoc analysis of another RCT found that metformin reduced fasting plasma glucose (FPG) levels in patients with upper-body obesity and metabolic syndrome (by 1999 World Health Organization criteria but not NCEP ATP III criteria).⁵

Investigators randomized 457 patients to metformin 850 mg once daily or placebo and followed them for a year. FPG levels decreased with metformin but increased with placebo (reduction FPG 5.9 mg/dL vs increase FPG 12.3 mg/dL; P<.04). The investigators didn’t report whether any patients developed diabetes.

However, another RCT (155 patients) that compared metformin 850 mg twice daily with placebo in subjects with metabolic syndrome but without diabetes found greater normalization of FPG (5% vs 0%; P=.005), but no reversal of metabolic syndrome or change in Framingham 10-year risk score after 12 weeks.⁶