Randomized Study of Metformin and Intensive Lifestyle Intervention on Cancer Incidence over 21 Years of Follow-up in the Diabetes Prevention Program.
Level 2 - randomized trial
Individual randomized controlled trial with long-term follow-up
PubMed 40243198 · doi:10.1158/1940-6207.CAPR-23-0461
What was done
The Diabetes Prevention Program randomized 3,234 adults at high risk of diabetes to intensive lifestyle intervention (ILS), metformin (850 mg twice daily), or blinded placebo between 1996 and 2001. During subsequent follow-up in the Diabetes Prevention Program Outcomes Study, all participants were offered a modified lifestyle intervention, and metformin continued in an open-label format. Participants reported cancer cases annually, and medical records were adjudicated for all reported events over a median follow-up of 21 years. The primary endpoint was total cancer incidence comparing metformin with placebo, with ILS versus placebo as a secondary objective.
What was found
After a median follow-up of 21 years, 546 participants developed a first incident cancer (173 metformin, 182 ILS, and 191 placebo). Cancer incidence rates per 1,000 person-years were 9.8 in the metformin group, 10.5 in the ILS group, and 10.8 in the placebo group. Hazard ratios compared with placebo were 0.90 (95% CI, 0.73–1.10) for metformin and 0.96 (95% CI, 0.79–1.18) for ILS. There were no statistically significant differences between treatment groups for obesity-related cancers or in sex-specific analyses.
Why it matters
Prior observational meta-analyses suggested metformin might lower cancer incidence by 10% to 40% in diabetic populations; these 21-year randomized data show no substantive preventive effect of metformin or intensive lifestyle intervention on overall or obesity-related cancer incidence in prediabetic adults.
Limits
The long-term follow-up was open-label after the initial trial phase, and nonstudy metformin use increased over time across arms as participants developed diabetes. In addition, the intensity of the lifestyle intervention diminished over the 21-year period, which may have attenuated observable differences between groups.
Cited by
- contradicts Metformin has been shown in short-term studies to possibly prevent cancer prophylactically.