Long-term effects and effect heterogeneity of lifestyle and metformin interventions on type 2 diabetes incidence over 21 years in the US Diabetes Prevention Program randomised clinical trial
An erratum to this article was published (Lancet Diabetes Endocrinol, Jun 2025 ↗)
Authors' conclusion
The large initial intervention effects seen in the DPP trial were followed by sustained reductions in cumulative diabetes incidence for 21 years. Intervention effects were heterogeneous according to some baseline variables. These findings could guide precision interventions to help address the current type 2 diabetes epidemic.
Study context
- Population
- Adults with prediabetes originally enrolled in the Diabetes Prevention Program (DPP); 67.9% female, mean baseline age 50.6 years (SD 10.7)
- Participants
- 3,195 original DPP participants
- Comparison
- ILS vs metformin vs placebo
- Primary endpoint
- Diabetes incidence defined by ADA criteria
- Follow-up
- ≈21 years (July 31, 1996, to Feb 23, 2020)
Methodological detailsDPP/DPP Outcomes Study (DPPOS), intention-to-treat, prespecified primary outcome, subgroup heterogeneity analysis, Follow-up 0.2 to 23.2 years (median 8.0 years [IQR 3.0 to 18.0]); considered a 21-year period
- DPP/DPPOS
- Intention-to-treat
- Prespecified primary outcome
- Subgroup heterogeneity analysis
- Follow-up 0.2 to 23.2 years (median 8.0 years [IQR 3.0 to 18.0]); considered a 21-year period
Primary result
As reported in the abstract
Diabetes incidence · ~21 years
Each group vs placeboHazard ratio (95% CI)
ILS
0.76(0.68–0.85)
Metformin
0.83(0.74–0.93)
Each group vs placeboRate difference, cases per 100 person-years (95% CI)
ILS
−1.59(−2.25 to −0.93)
Metformin
−1.17(−1.85 to −0.49)
Further findings
| Outcome | Increase in mean diabetes-free survival (years) (95% CI) | |
|---|---|---|
| Diabetes-free survival increase vs placebo · ≈21 yearsILSvs Placebo | 2.0 (1.2–2.8) | |
| Diabetes-free survival increase vs placebo · ≈21 yearsMetforminvs Placebo | 1.2 (0.4–2.0) | |
| −2024Difference, years (linear scale) |
Years
- Diabetes-free survival increase vs placebo — Increase in median diabetes-free survival, ILS vs placebo
- 3.5
- Diabetes-free survival increase vs placebo — Increase in median diabetes-free survival, metformin vs placebo
- 2.5
Course of cumulative incidence
- Curves separated early, especially in first 3 years; metformin and ILS curves progressively converged; overall effects appeared to result from large early effects during DPP
Effect heterogeneity (RDs vs placebo) by baseline risk factors
- Greater absolute ILS effect with higher baseline fasting glucose, HbA1c, and multivariable clinical and physiological risk indices
- Greater absolute metformin effect in younger participants
Original publication
Long-term effects and effect heterogeneity of lifestyle and metformin interventions on type 2 diabetes incidence over 21 years in the US Diabetes Prevention Program randomised clinical trial. Lancet Diabetes Endocrinol. Published 28 April 2025. doi:10.
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