Metformin Linked to Better Long-term Weight Loss

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Among patients who successfully lost weight in the Diabetes Prevention Program (DPP) study, long-term maintenance of weight loss is better for those initially assigned to metformin compared to a lifestyle intervention, reports a study in Annals of Internal Medicine.

In the original DPP, 3234 overweight or obese patients with elevated glucose levels were randomly assigned to metformin, an intensive lifestyle intervention, or placebo. At an average follow-up of 2.8 years, diabetes risk was reduced by 31% with metformin and 58% with the lifestyle intervention, compared to placebo. Weight loss averaged 2.1 and 5.6 kg, respectively, and was the main factor responsible for diabetes prevention. At 1 year, 28.5% of patients in the metformin group, 62.6% in the lifestyle intervention group, and 13.4% in the placebo group had lost at least 5% of body weight.

In the DPP Outcomes Study (DPPOS), 1066 patients with at least 5% weight loss were followed up for 15 years, after the end of masked treatment. Long-term weight loss management was compared among patients in the three DPP intervention groups. Baseline and post-baseline factors associated with maintenance of weight loss were assessed as well.

From year 6 to 15, mean weight loss relative to baseline was 6.2% in patients originally assigned to metformin, compared to 3.7% in those assigned to the lifestyle intervention and 2.8% in the placebo group. Mean percentages of patients with long-term weight loss throughout follow-up were 56.5%, 48.9%, and 41.7%, respectively.

Across groups, greater weight loss in year 1 was significantly related to long-term weight loss. Other independent predictors included continued metformin use in the metformin group, absence of diabetes or family history of diabetes in the lifestyle intervention group, and higher fasting plasma glucose in the placebo group.

Among patients who initially lost at least 5% of body weight in the DPP, long-term maintenance of weight loss in the DPPOS is greatest for those originally assigned to metformin. Older age and initial weight loss are key predictors of maintenance of weight loss over 15 years. The researchers call for further studies of metformin to promote weight loss maintenance, whether initial weight loss is achieved with lifestyle interventions, anti-obesity drugs or devices, or bariatric surgery [Apolzan JW, et al. Long-term weight loss with metformin or lifestyle intervention in the Diabetes Prevention Program Outcomes Study. Ann Intern Med 2019; DOI: 10.7326/M18-1605].