Metformin More Effective For Weight Loss Maintenance Than Lifestyle Alone Interview with:
Kishore M. Gadde, MD, Professor
Fairfax Foster Bailey Endowed Chair in Heart Disease Prevention
Medical Director, Clinical Services
Pennington Biomedical Research Centre
Baton Rouge, LA 70808 What is the background for this study?

Response: Around 20 years ago, the Diabetes Prevention Program, DPP, enrolled 3,234 adults with excess body weight and impaired glucose tolerance. The idea was to compare the efficacy of either an intensive lifestyle intervention or metformin relative to placebo in preventing diabetes. Over approximately 3 years, both lifestyle and metformin were effective, but lifestyle intervention was better for weight loss as well as in reducing the risk of diabetes. After the blinded treatment phase ended, the researchers continued to follow this cohort in their originally randomised groups. What are the main findings?

Response: In the current investigation, the researchers examined long-term weight changes over 15 years among those achieving clinically significant weight loss (defined as 5% or greater) in the first year. Lifestyle therapy group had greater average weight loss at 1 year. However, the lifestyle group regained substantial weight between years 2 and 5.

During the last 10-year period (Years 6 to 15) of the 15-year follow-up, the average weight losses for the metformin and lifestyle groups were 6.2% and 3.7%, respectively, a difference of 2.5% favouring metformin.  Among these participants achieving significant weight loss at 1 year, their average weight losses at Year 15 were 8.2% for the metformin group and 3.7% for the lifestyle group. The percentages of those with at least 5% weight loss were also higher in the metformin group than in the lifestyle group during last 10 years and at Year 15.

In summary, although lifestyle therapy was initially superior for weight loss, metformin appeared to be more effective for weight loss maintenance as years went by. The longer the follow-up, the more striking was the difference in the average weight loss between the metformin and lifestyle groups. The degree of weight loss in the first year predicted long-term weight loss for all treatment groups. What should readers take away from your report?

Response: Metformin, the commonly used diabetes drug, does not induce significant weight loss for all people who take it. However, people who achieve 5% or more weight loss after about a year may be able to maintain that weight loss for several years, if they continue taking metformin.

Early weight loss determines long-term weight loss. What recommendations do you have for future research as a result of this work?

Response: Since most people with obesity can achieve a good amount of weight loss with diet and exercise over 3-6 months, topics for future research are:

  • Can metformin help sustain the weight loss achieved with diet and exercise?
  • Can clinicians treat patients needing to lose weight initially with a low-calorie diet and switch them to metformin therapy for weight loss maintenance?
  • Can metformin enhance weight loss among people who had bariatric surgery, stopped losing weight after a few months to a year, but need to lose more weight?
  • Can metformin prevent weight regain after initially losing weight with diets, expensive weight loss drugs, and bariatric surgery?These are some of the questions that need to be answered by conducting randomised controlled trials.

Disclosures: Unrelated to the current investigation, Dr. Gadde received research funding and other payments to his institution from AstraZeneca. The company’s products are not mentioned in the paper. He has not received any direct payments from commercial entities for over 10 years.


Apolzan JW, Venditti EM, Edelstein SL, Knowler WC, Dabelea D, Boyko EJ, et al. Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study. Ann Intern Med. [Epub ahead of print 23 April 2019] doi: 10.7326/M18-1605

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Last Updated on April 23, 2019 by Marie Benz MD FAAD