Metformin associated with more long-term weight loss than lifestyle change in prediabetes patients

Participants in the Diabetes Prevention Program (DPP) who were randomly assigned to metformin had greater weight loss during follow-up years 6 to 15 than those assigned to an intensive lifestyle intervention or placebo, a study found.

The DPP compared metformin, intensive lifestyle intervention, or placebo for the prevention of type 2 diabetes among overweight or obese patients with elevated glucose levels. The intensive lifestyle intervention comprised a 16-session behavior modification intervention conducted over six to eight months, followed by individual and group reinforcement every two months. The DPP Outcomes Study (DPPOS) observed patients after the masked treatment phase (average follow-up of 3.2 years) ended. Results were published April 23 by Annals of Internal Medicine.

Of the 3,234 randomly assigned participants from 27 DPP and DPPOS clinics, 1,066 lost at least 5% of baseline weight in the first year. This group included 289 (28.5%) participants in the metformin group, 640 (62.6%) in the intensive lifestyle group, and 137 (13.4%) in the placebo group, and these patients were less likely to develop diabetes over 15-year follow-up. After the masked treatment phase ended, the mean weight loss relative to baseline that was maintained between years 6 and 15 was 6.2% (95% CI, 5.2% to 7.2%) in the metformin group, 3.7% (95% CI, 3.1% to 4.4%) in the lifestyle intervention group, and 2.8% (95% CI, 1.3% to 4.4%) in the placebo group.

In all three groups, patients who lost more weight in the first year were more likely to have long-term weight loss. Among those randomized to metformin, older age and continued metformin use were independent predictors. For the lifestyle group, older age and absence of either diabetes or a family history of diabetes was predictive, while higher fasting plasma glucose levels at baseline were a predictor in the placebo group.

Older age and the amount of weight initially lost were the most consistent predictors of maintaining long-term weight loss. Although twice as many participants in the lifestyle intervention group versus the metformin group lost at least 5% of their weight in the first year, those who were originally assigned to metformin had greater success in maintaining weight loss, the study authors noted.

“From a population health perspective, this finding gains importance with increasing dissemination and implementation of DPP-modeled lifestyle programs and reimbursement for such interventions,” the authors wrote.

An editorial noted that modest weight loss decreases risk for progression to diabetes, so while not every patient can achieve long-term weight loss, it makes sense to encourage it for all. “Unfortunately, the DPP did not include a combined ILS [intensive lifestyle intervention] and metformin group, so we do not know whether the 2 interventions are synergistic, particularly for initial weight loss,” the editorial said. “For now, clinical judgment should be used to decide whether metformin should be added if ILS does not succeed or if the patient subsequently regains the weight they lost.”