Metformin use lowered rates of all-cause mortality in a study of patients with type 2 diabetes who had a high risk of cardiovascular events (CV), according to investigators. Treatment with drug, however, did not lower rates of a composite end point of CV death, myocardial infarction, or ischemic stroke.
The finding is from a post hoc analysis of the SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53) trial and included 12,156 patients who had baseline biomarker samples. Of these patients, 8971 (74%) had taken metformin, 1611 (13%) had prior heart failure, and 1332 (11%) had at least moderate chronic kidney disease (CKD), defined as an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or below. Although the risk of the composite end point was similar between patients who had ever used metformin and those who never did, the metformin group had a significant 25% decreased risk of death from any cause in adjusted analyses, Brian A. Bergmark, MD of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues reported in Circulation.
The investigators found no significant association between these end points and metformin use among patients with prior HF or moderate to severe CKD.
In a previous systematic review of 17 observational studies published in the Annals of Internal Medicine in 2017, researchers concluded that metformin use is associated with decreased all-cause mortality in patients with CKD, congestive heart failure, or chronic liver disease with hepatic impairment.
SAVOR-TIMI 53 was a randomized, double-blind, placebo-controlled trial evaluating the cardiovascular efficacy and safety of saxaglipitin, a dipeptidyl peptidase 4 inhibitor, when added to standard of care in patients with type 2 diabetes. A previous study of 16,492 participants published in Diabetes Care in 2017 found that saxagliptin was associated with improvement in and/or less deterioration in albumin-creatinine ratio from baseline to the end of the trial among patients with baseline normo-, micro-, and macroalbuminuria, with no effect on eGFR.
Bergman BA, Bhatt DL, McGuire DK, et al. Metformin use and clinical outcomes among patients with diabetes with or without heart failure or kidney dysfunction: Observations from the SAVOR-TIMI 5 trial. Circulation. 2019.
Crowley MJ, Diamantidis CJ, McDuffie JR, et al. Chronic outcomes of metformin use in populations with chronic kidney disease, congestive heart failure, or chronic liver disease: A systematic review. Ann Intern Med. 2019;166:191-200. doi: 10.7326/M16-1901
Mosenzon O, Leibowitz G, Bhatt DL, et al. Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial. Diabetes Care. 2017;40:69-76.