Randomized Controlled Trial Multicenter Study Comparative Study
Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes.
- Hertzel C Gerstein, Naveed Sattar, Julio Rosenstock, Chinthanie Ramasundarahettige, Richard Pratley, Renato D Lopes, LamCarolyn S PCSPFrom the Population Health Research Institute, Hamilton Health Sciences (H.C.G., C.R., L.H., L.D.), and McMaster University (H.C.G.) - both in Hamilton, ON, Canada; the Institute of Cardiovascular and Medical Sciences, University of Glasg, Nardev S Khurmi, Laura Heenan, Stefano Del Prato, Leanne Dyal, Kelley Branch, and AMPLITUDE-O Trial Investigators.
- From the Population Health Research Institute, Hamilton Health Sciences (H.C.G., C.R., L.H., L.D.), and McMaster University (H.C.G.) - both in Hamilton, ON, Canada; the Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (N.S.); the Dallas Diabetes Research Center at Medical City, Dallas (J.R.); AdventHealth Translational Research Institute, Orlando, FL (R.P.); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (R.D.L.); National Heart Centre Singapore and Duke-National University of Singapore, Singapore (C.S.P.L.); Sanofi, Bridgewater, NJ (N.S.K.); the Section of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (S.D.P.); and the Division of Cardiology, University of Washington, Seattle (K.B.).
- N. Engl. J. Med. 2021 Sep 2; 385 (10): 896-907.
BackgroundFour glucagon-like peptide-1 (GLP-1) receptor agonists that are structurally similar to human GLP-1 have been shown to reduce the risk of adverse cardiovascular events among persons with type 2 diabetes. The effect of an exendin-based GLP-1 receptor agonist, efpeglenatide, on cardiovascular and renal outcomes in patients with type 2 diabetes who are also at high risk for adverse cardiovascular events is uncertain.MethodsIn this randomized, placebo-controlled trial conducted at 344 sites across 28 countries, we evaluated efpeglenatide in participants with type 2 diabetes and either a history of cardiovascular disease or current kidney disease (defined as an estimated glomerular filtration rate of 25.0 to 59.9 ml per minute per 1.73 m2 of body-surface area) plus at least one other cardiovascular risk factor. Participants were randomly assigned in a 1:1:1 ratio to receive weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg or placebo. Randomization was stratified according to use of sodium-glucose cotransporter 2 inhibitors. The primary outcome was the first major adverse cardiovascular event (MACE; a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or undetermined causes).ResultsA total of 4076 participants were enrolled; 2717 were assigned to receive efpeglenatide and 1359 to receive placebo. During a median follow-up of 1.81 years, an incident MACE occurred in 189 participants (7.0%) assigned to receive efpeglenatide (3.9 events per 100 person-years) and 125 participants (9.2%) assigned to receive placebo (5.3 events per 100 person-years) (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P<0.001 for noninferiority; P = 0.007 for superiority). A composite renal outcome event (a decrease in kidney function or macroalbuminuria) occurred in 353 participants (13.0%) assigned to receive efpeglenatide and in 250 participants (18.4%) assigned to receive placebo (hazard ratio, 0.68; 95% CI, 0.57 to 0.79; P<0.001). Diarrhea, constipation, nausea, vomiting, or bloating occurred more frequently with efpeglenatide than with placebo.ConclusionsIn this trial involving participants with type 2 diabetes who had either a history of cardiovascular disease or current kidney disease plus at least one other cardiovascular risk factor, the risk of cardiovascular events was lower among those who received weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg than among those who received placebo. (Funded by Sanofi; AMPLITUDE-O ClinicalTrials.gov number, NCT03496298.).Copyright © 2021 Massachusetts Medical Society.
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