Metformin and mortality. Reply to Lund SS [letter]
- 561 Downloads
KeywordsMeta-analysis Metformin Neoplasms Systematic review
UK Prospective Diabetes Study
To the Editor: We thank Dr Lund for his comments  on our analysis of cancer incidence and mortality in randomised trials of metformin  and confirm that the Hyperinsulinaemia: the Outcome of its Metabolic Effects (HOME) trial  was excluded because it did not meet our sample size inclusion criterion.
Summary relative risks (RR), with 95% CIs and I2 statistics for heterogeneity, for all-cause mortality in trials randomising participants to receive metformin or placebo/usual care, across all trials and in sensitivity analyses excluding each trial in turn
RR (95% CI)
None (main analysis)
0.91 (0.70, 1.18)
Diabetes Prevention Program (DPP) 
0.90 (0.68, 1.17)
Early Diabetes Intervention Trial (EDIT) 
0.91 (0.70, 1.20)
Indian Diabetes Prevention Program (IDPP) 
0.91 (0.70, 1.19)
Pfützner et al 2011 
0.90 (0.69, 1.18)
UKPDS trial in overweight patients (UKPDS-O) 
1.43 (0.95, 2.13)
UKPDS trial in sulfonylurea failure (UKPDS-S) 
0.67 (0.49, 0.93)
We believe that the remarks in our paper that the summary estimates ‘are dominated by the two large trials from the UKPDS group, which appear to show for metformin effects in opposite directions’ and that our analyses have limitations to be overcome by future randomised trials, remain justified. We re-emphasise our observation that the average follow-up for mortality in our analysis is just 2.8 years, and that our results for all-cause mortality in particular are unlikely to fully reflect the long-term effects of metformin.
Duality of interest
R. R. Holman has, in the last 12 months, received research support from Amylin, Bayer, Merck and Novartis; attended advisory boards with Amylin, Lilly, Merck, Novartis and Novo Nordisk; and given lectures supported by Bayer, Lilly, Merck and Novo Nordisk. R. J. Stevens and B. J. Cairns have no conflicts of interest associated with this letter.
RJS, BJC and RRH were responsible for the conception and design of the manuscript, drafting the article and revising it. RJS carried out statistical analyses. All authors approved the version to be published. The authors are writing on behalf of the Metformin Trialists’ Collaboration.
- 1.Lund SS (2013) Metformin and mortality. Diabetologia. doi:10.1007/s00125-013-2843-y
- 6.Holman RR, Blackwell L, Stratton IM, Manley SE, Tucker L, Frighi V (2003) Six-year results from the Early Diabetes Intervention Trial. Diabet Med 20:15, AbstractGoogle Scholar
- 7.Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V (2006) The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia 49:289–297PubMedCrossRefGoogle Scholar