Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study

Ann Intern Med. 2019 May 21;170(10):682-690. doi: 10.7326/M18-1605. Epub 2019 Apr 23.


Background: Identifying reliable predictors of long-term weight loss (LTWL) could lead to improved weight management.

Objective: To identify some predictors of LTWL.

Design: The DPP (Diabetes Prevention Program) was a randomized controlled trial that compared weight loss with metformin, intensive lifestyle intervention (ILS), or placebo. Its Outcomes Study (DPPOS) observed patients after the masked treatment phase ended. (ClinicalTrials.gov: NCT00004992 and NCT00038727).

Setting: 27 DPP and DPPOS clinics.

Participants: Of the 3234 randomly assigned participants, 1066 lost at least 5% of baseline weight in the first year and were followed for 15 years.

Measurements: Treatment assignment, personal characteristics, and weight.

Results: After 1 year, 289 (28.5%) participants in the metformin group, 640 (62.6%) in the ILS group, and 137 (13.4%) in the placebo group had lost at least 5% of their weight. 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% (CI, 3.1% to 4.4%) in the ILS group, and 2.8% (CI, 1.3% to 4.4%) in the placebo group. Independent predictors of LTWL included greater weight loss in the first year in all groups, older age and continued metformin use in the metformin group, older age and absence of either diabetes or a family history of diabetes in the ILS group, and higher fasting plasma glucose levels at baseline in the placebo group.

Limitation: Post hoc analysis; examination of nonrandomized subsets of randomized groups after year 1.

Conclusion: Among persons with weight loss of at least 5% after 1 year, those originally randomly assigned to metformin had the greatest loss during years 6 to 15. Older age and the amount of weight initially lost were the most consistent predictors of LTWL maintenance.

Primary funding source: National Institutes of Health.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Video-Audio Media

MeSH terms

  • Diabetes Mellitus, Type 2 / prevention & control*
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Life Style*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • United States
  • Weight Loss / drug effects*


  • Hypoglycemic Agents
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT00004992
  • ClinicalTrials.gov/NCT00038727