← Diet, exercise & lifestyle × all-cause mortality

TrialThe lancet. Diabetes & endocrinology2025

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.

William C Knowler et al.PubMed ↗Full text ↗Publisher ↗

  • Intensive lifestyle intervention (ILS)looks good hereLower diabetes incidence rate, higher diabetes-free survival.Randomised, large.
  • Metforminlooks good hereLower diabetes incidence rate, higher diabetes-free survival.Randomised, large.

What the trial testedrandomised · 3,234 people · 2025

Randomised vs placebo

Lowered diabetes incidence rate

−24%−32% to −15%

intensive lifestyle intervention (ILS) vs placebo

Bigger than 7 in 10 for all-cause mortality

As reported

HR 0.76, 95% CI 0.68–0.85

Randomised vs placebo

Lowered diabetes incidence rate

−1.59−2.25 to −0.93

intensive lifestyle intervention (ILS) vs placebo

As reported

difference −1.59, 95% CI −2.25 to −0.93

Randomised vs placebo

Lowered diabetes incidence rate

−17%−26% to −7%

metformin vs placebo

Bigger than 5 in 10 for all-cause mortality

As reported

IRR 0.83, 95% CI 0.74–0.93

Randomised vs placebo

Lowered diabetes incidence rate

−1.17−1.85 to −0.49

metformin vs placebo

As reported

difference −1.17, 95% CI −1.85 to −0.49

+2 more in the walkthrough ↓

Who was studied, and how

3,234people with type 2 diabetes, in this paper

The trial randomly assignedassigned by chance

intensive lifestyle intervention (ILS)
placebo

Lowered diabetes incidence rate−24%

Raised diabetes-free survival+2.00

randomised

The trial randomly assignedassigned by chance

metformin
placebo

Lowered diabetes incidence rate−17%

Raised diabetes-free survival+1.20

randomised

the abstract, start to end

… original ILS group (hazard ratio [HR] 0.76 [95% CI 0.68 to 0.85], rate difference [RD] -1.59 cases [95% CI -2.25 to -0.93] per 100 person-years) and in the original metformin group (HR 0.83 [0.74 to 0.93], RD -1.17 [-1.85 to -0.49]), with corresponding increases in median diabetes-free survival of 3.5 years and 2.5 years, and mean diabetes-free survival of 2.0 years (95% CI 1.2 to 2.8) and 1.2 years (0.4 to …

← favours treatmentfavours comparator →
could be chance
Diabetes incidence rateintensive lifestyle intervention (ILS) vs placebo
HR 0.760.68–0.85
Diabetes incidence rateintensive lifestyle intervention (ILS) vs placebo
−1.59−2.25 to −0.93
Diabetes incidence ratemetformin vs placebo
IRR 0.830.74–0.93
Diabetes incidence ratemetformin vs placebo
−1.17−1.85 to −0.49
Mean diabetes-free survivalintensive lifestyle intervention (ILS) vs placebo
2.01.20–2.80
Mean diabetes-free survivalmetformin vs placebo
1.20.40–2.00
MetforminDiet, exercise & lifestyleAll-cause mortality

Diet, exercise & lifestyle × all-cause mortalityhelps?one trial

unlikelylikely
0.500.50 without it

Metformin × all-cause mortalityhelps?one trial

unlikelylikely
0.500.50 without it
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19 papers cite it

2025
2026
this paperpooled ittrialcites it

2 trials

NCT00004992phase 33,234 enrolled1996NCT00038727phase 32,779 enrolled1996
Full record →Abstract, authors, funding and every citing paper · PMID 40311647