Response by Bergmark et al to Letter Regarding Article, "Metformin Use and Clinical Outcomes Among Patients With Diabetes Mellitus With or Without Heart Failure or Kidney Dysfunction: Observations From the SAVOR-TIMI 53 Trial".
Abstract
January 28, 2020 e57 Brian A. Bergmark, MD Deepak L. Bhatt, MD, MPH Darren K. McGuire, MD, MHSc Benjamin M. Scirica, MD, MPH In Response: We appreciate the letter written by Drs Mordi, Mohan, and Lang describing their findings of reduced left ventricular mass index in patients with coronary artery disease and insulin resistance or pre–diabetes mellitus randomized to 12 months of treatment with metformin compared with placebo. The observation we recently reported in Circulation1 of an association between metformin exposure and a lower rate of all-cause mortality in the SAVOR-TIMI 53 trial (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus–Thrombolysis in Myocardial Infarction) is hypothesis-generating. We agree with Drs Mordi, Mohan, and Lang that identifying potential mechanism(s) of cardiovascular benefit with metformin is of high scientific interest. Numerous theories exist,2 though few have been tested as rigorously as in the MET-REMODEL trial (Metformin and its Effects on Left Ventricular Hypertrophy in Normotensive Patients With Coronary Artery Disease).3 Recent experience with cardiovascular outcomes trials of the sodium-glucose cotransporter 2–inhibitors and the glucagon-like peptide-1 receptor agonists reinforces the importance of appropriately powered randomized, controlled trials that can drastically change the paradigm of treatment of cardiometabolic disease even in the absence of a clear mechanism for risk reduction.4,5 We…
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