Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials
| Autor: | Benjamin J Cairns, A. Ramachandran, Giancarlo Viberti, Richard Stevens, Clare Bankhead, R P Camisasca, Steven E. Kahn, Sian Harrison, Annette Plüddemann, Jennifer Hirst, Francesca L. Crowe, Anja Schweizer, Andrew Farmer, Raghib Ali, Nia Roberts, Peter W Rose, M A Bethel, Rafael Perera, Philip Home, Rury R. Holman, Julie McLellan |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
business.industry Endocrinology Diabetes and Metabolism Cancer Subgroup analysis Placebo medicine.disease law.invention Surgery Clinical trial Randomized controlled trial law Meta-analysis Internal medicine Internal Medicine Medicine Observational study business Survival rate |
| Popis: | AIMS/HYPOTHESIS: Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs). METHODS: RCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I (2)statistics for heterogeneity were calculated by fixed effects meta-analysis. RESULTS: Of 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials. CONCLUSIONS/INTERPRETATION: Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality. |
| Databáze: | OpenAIRE |
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