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

Abstract

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.

Figure 1.. Patterns of weight changes over 15 years.

(A) Shown is the observed percent weight loss over 15 years for all participants by treatment group and for the subsets of participants who achieved <5% or ≥5% weight loss at Year 1. Data shown are Mean ± 95% Confidence Intervals (CI). (B) Shown are the observed percentages of participants by treatment group achieving ≥5% weight loss yearly during Years 2–15 among participants who achieved ≥5% weight loss at Year 1. Data shown are Mean ± 95% CI. Sample sizes: Metformin Year 1: 289, Year 5: 247, Year 10: 236. Year 15: 172. Intensive Lifestyle: Year 1: 640, Year 5: 540, Year 10: 491, Year 15: 373. Placebo: Year 1: 137, Year 5: 110, Year 10: 104, Year 15: 92.

Figure 2.. Predictors of long-term weight loss.

Metformin (A), Intensive Lifestyle (ILS) (B), and Placebo (C). GEE and Multiple Logistic Regression Models Predicting ≥ 5% Weight Loss overall and at 5, 10, and 15 years (Odds Ratios & 95% CI). Odds ratios are displayed on a log scale. With Metformin (A), older age at randomization (per 10 years), greater % weight loss at Year 1 (per 5%), and active use of study metformin increased odds of long-term weight loss (LTWL). With ILS (B), older age at randomization (per 10 years) and greater % weight loss at Year 1 (per 5%) increased odds of LTWL, and current diabetes status, and a family history of diabetes decreased the odds of LTWL. With Placebo (C), greater % weight loss at Year 1 (per 5%) and higher fasting glucose (per 0.55 mmol/L [10 mg/dl]) were the only predictors of LTWL. ILS = intensive lifestyle; LTWL = long-term weight loss