Abstract
Aims: Metformin could have benefits on cardiovascular disease and kidney disease progression but is often withheld from individuals with diabetes and chronic kidney disease (CKD) because of a concern that it may increase the risk of lactic acidosis. Materials and methods: All-cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metformin users and non-users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin-alfa) Therapy (TREAT) (NCT00093015). Outcomes were compared after propensity matching of users and non-users and in multivariable proportional hazards models. Results: There were 591 individuals who used metformin at baseline and 3447 non-users. Among propensity-matched users, the crude incidence rate for mortality, cardiovascular mortality, cardiovascular events and the combined endpoint was lower in metformin users than in non-users, but ESRD was marginally higher (4.0% vs 3.6%). Metformin use was independently associated with a reduced risk of all-cause mortality (HR, 0.49; 95% CI, 0.36-0.69), cardiovascular death (HR, 0.49; 95% CI, 0.32-0.74), the cardiovascular composite (HR, 0.67, 95% CI, 0.51-0.88) and the kidney disease composite (HR, 0.77; 95% CI, 0.61-0.98). Associations with ESRD (HR, 1.01; 95% CI, 0.65-1.55) were not significant. Results were qualitatively similar in adjusted analyses of the full population. Two cases of lactic acidosis were observed. Conclusions: Metformin may be safer for use in CKD than previously considered and may lower the risk of death and cardiovascular events in individuals with stage 3 CKD.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1199-1208 |
| Number of pages | 10 |
| Journal | Diabetes, Obesity and Metabolism |
| Volume | 21 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2019 |
Funding
M. P. has received research grant support from Amgen, Celladon, Novartis and Sanofi (significant); has received consultantcy fees from Bayer, Genzyme, GlaxoSmithKline, Janssen, Lilly, Medicines Company, Merck, Novartis, Novo Nordisk, Relypsa, Salix, Sanofi, Thrasos and Vericel (modest) and from Boehringer Ingelheim, DalCor and Teva (significant); and holds stock options in DalCor. D. C. has received a research grant from Janssen Pharmaceuticals (significant) and funds for service from DSMB-Astra Zeneca. S. S. has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, BMS, Celladon, Gilead, GSK, Ionis, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Novartis, Sanofi Pasteur and Theracos; and has received consulting fees from Akros, Alnylam, Amgen, AstraZeneca, Bayer, BMS, Corvia, Gilead, GSK, Ironwood, Merck, Novartis, Pfizer, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, Abiomed and Janssen. A. K. S. has received a research grant from Glaxo Smith Kline (significant). A. L. has received a research grant from Amgen as a member of the TREAT Steering Committee. E. B. has received fees for consultancy and Advisory Board membership from Fresenius (modest). J. M. has received grants from Dexcom, Novartis, AZ/BMS, Medtronic (significant); has received fees for Advisor/Consultant from Bayer, BI/Lilly, NovoNordisk (modest); has received fees for Speakers' Bureau from Janssen (significant), Dexcom (modest), Mannkind (modest) and Aegerion (modest). E. L. has received a research grant from Sanofi (significant).
Keywords
- cardiovascular disease
- diabetes complications
- diabetic nephropathy
- metformin
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Endocrinology
