Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes
Por:
Gerstein, HC, Sattar, N, Rosenstock, J, Ramasundarahettige, C, Pratley, R, Lopes, RD, Lam, CSP, Khurmi, NS, Heenan, L, Del Prato, S, Dyal, L, Branch, K, Sionis A., AMPLITUDE-O Trial Investigators
Publicada:
2 sep 2021
Ahead of Print:
1 jun 2021
Resumen:
Cardiovascular and Renal Outcomes with Efpeglenatide This trial compared weekly injections of efpeglenatide, an exendin-based glucagon-like peptide-1 receptor agonist, at a dose of 4 or 6 mg with placebo in participants with known type 2 diabetes and 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 with efpeglenatide.
Background Four 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. Methods In 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 m(2) 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). Results A 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. Conclusions In 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, .)
Filiaciones:
Gerstein, HC:
Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada
McMaster Univ, Hamilton, ON, Canada
Sattar, N:
Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland
Rosenstock, J:
Dallas Diabet Res Ctr Med City, Dallas, TX USA
Ramasundarahettige, C:
Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada
Pratley, R:
AdventHlth Translat Res Inst, Orlando, FL USA
Lopes, RD:
Duke Univ, Duke Clin Res Inst, Med Ctr, Durham, NC USA
Lam, CSP:
Natl Heart Ctr Singapore, Singapore, Singapore
Duke Natl Univ Singapore, Singapore, Singapore
Khurmi, NS:
Sanofi, Bridgewater, NJ USA
Heenan, L:
Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada
Del Prato, S:
Univ Pisa, Sect Metab Dis & Diabet, Dept Clin & Expt Med, Pisa, Italy
Dyal, L:
Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada
Branch, K:
Univ Washington, Div Cardiol, Seattle, WA 98195 USA
Sionis A.:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Green Accepted
|