Abstract 16764: Metformin Use and Clinical Outcomes Among Patients With Diabetes Mellitus and Heart Failure or Kidney Dysfunction - Observations From the SAVOR-TIMI 53 Trial
Introduction: Metformin is the recommended first line therapy for T2DM. The safety of metformin in patients with heart failure (HF) or chronic kidney disease (CKD) remains uncertain.
Hypothesis: Metformin is not associated with increased cardiovascular risk, even in patients with HF or CKD.
Methods: Patients in SAVOR-TIMI 53 (NCT01107886) were classified as ever vs never taking metformin during the trial period. Treatment effects of metformin were estimated with Cox models for the primary endpoint (PEP) (CV death, MI, or ischemic stroke), CV death, and all-cause mortality using 3,509 propensity-score matched pairs based on metformin exposure. Additional sensitivity analyses were done using a weighted Cox model with inverse probability of treatment weighting (IPTW) in the entire SAVOR population.
Results: Of the 16,492 patients randomized, 12,155 (74%) had metformin exposure, including 10.2% with HF and 5.8% with CKD (eGFR ≤ 45 mL/min). Overall, in propensity-matched cohort analyses, metformin was associated with a lower risk of the PEP (HR 0.80 [0.67-0.95]), CV death (HR 0.74 [0.57-0.95]), and all-cause mortality (HR 0.75 [0.61-0.92]). In IPTW analyses, among patients without HF (n=14,387) or CKD (n=14,706), metformin was also associated with a lower risk of the PEP, overall mortality, and CV death (Figure). In contrast, there was no relationship between metformin and cardiovascular outcomes in patients with HF (n=2,105) and/or CKD (n=1,786) (p for interaction between metformin, HF and CKD, and outcomes all <0.05) (Figure).
Conclusion: In this large clinical trial, metformin use was associated with a lower CV risk among patients without HF or CKD, supporting the use of metformin as first-line therapy in T2DM. Metformin was also used frequently in patients with HF and/or CKD, with heterogeneity of its association with outcomes in these high-risk subgroups demonstrating neither CV benefit nor harm associated with metformin.
Author Disclosures: B.A. Bergmark: None. D.L. Bhatt: Research Grant; Significant; AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb Company. D. McGuire: Consultant/Advisory Board; Modest; Boehringer-Ingelheim, Janssen R&D, Sanofi-Aventis Group, Merck Sharp & Dohme, Daiichi Sankyo, Lilly USA, Novo Nordisk, GlaxoSmithKline, Takeda Pharmaceuticals, AstraZeneca, Lexicon, Regeneron, University of Oxford, Duke Clinical Research Institute, Partners Healthcare, Cleveland Clinic Foundation, Eisai. A. Cahn: Consultant/Advisory Board; Modest; AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Novo Nordisk, Sanofi. O. Mosenzon: None. P.G. Steg: Research Grant; Significant; Sanofi, Servier, Merck. Consultant/Advisory Board; Modest; Amarin, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL-Behring, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Janssen, Novartis, Pfizer, The Medicines Company, Regeneron, Roche. Consultant/Advisory Board; Significant; AstraZeneca, Sanofi, Servier. K. Im: None. E. Kanevsky: None. I. Raz: None. E. Braunwald: Research Grant; Modest; Astra Zeneca, Johnson & Johnson, Bristol Myers Squibb, Merck & Co., Daiichi Sankyo, Glaxo Smith Kline, Sanofi Aventis, Duke University and Novartis.. Honoraria; Modest; Merck & Co (no compensation), The Medicines Co., Medscape, Bayer, Daiichi Sankyo, Menarini International, Sanofi, Novartis (Uncompensated). B.M. Scirica: Research Grant; Significant; AstraZeneca, Eisai, Merck, Poxel. Consultant/Advisory Board; Modest; GE Healthcare, Lexicon, Merck, Health@Scale, Biogen Idec. Consultant/Advisory Board; Significant; Significant, Boehringer Ingelheim, Covance, Dr. Reddy’s Laboratory, Elsevier Practice Update Cardiology, GlaxoSmithKline, St. Jude Medical.
- © 2016 by American Heart Association, Inc.