Efpeglenatide and clinical outcomes with and without concomitant sodium-glucose co-transporter-2 inhibition use in type 2 diabetes: exploratory analysis of the AMPLITUDE-O trial

Lam, C. S.P. et al. (2022) Efpeglenatide and clinical outcomes with and without concomitant sodium-glucose co-transporter-2 inhibition use in type 2 diabetes: exploratory analysis of the AMPLITUDE-O trial. Circulation, 145(8), pp. 565-574. (doi: 10.1161/CIRCULATIONAHA.121.057934) (PMID:34775781)

Abstract

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) both reduce cardiovascular (CV) events among patients with type 2 diabetes. However, no CV outcome trial has evaluated the long-term effects of their combined use. The AMPLITUDE-O trial reported that once weekly injections of the GLP-1 RA efpeglenatide (vs. placebo) reduced major adverse cardiovascular events (MACE); MACE, coronary revascularization or unstable angina hospitalization (expanded MACE); a renal composite outcome; and MACE or death in people with type 2 diabetes and CV and/or renal disease. The trial uniquely stratified randomization by baseline or anticipated use of SGLT2 inhibitors and included the highest prevalence at baseline (N=618, 15.2%) of SGLT2 inhibitor use among GLP-1 RA CV outcome trials to date. Its results were analyzed to estimate the combined effect of SGLT2 inhibitors and efpeglenatide on clinical outcomes. Methods: Cardiovascular and renal outcomes were analyzed using Cox proportional hazards models adjusted for region, SGLT2 inhibitor randomization strata, and the SGLT2 inhibitor-by-treatment interaction. Continuous variables were analyzed using a mixed-effects models for repeated measures that also included an interaction term. Results: The effect (hazard ratio [95% confidence interval]) of efpeglenatide versus placebo in the absence and presence of baseline SGLT2 inhibitors, respectively, on MACE (0.74 [0.58- 0.94] and 0.70 [0.37- 1.30]), expanded MACE (0.77 [0.62- 0.96] and 0.87 [0.51- 1.48]), renal composite (0.70 [0.59- 0.83] and 0.52 [0.33- 0.83]), and MACE or death (0.74 [0.59- 0.93] and 0.65 [0.36- 1.19]) did not differ by baseline SGLT2 inhibitor use (P for all interactions >0.2). Efpeglenatide's reduction of blood pressure, body weight, low density lipoprotein cholesterol and urinary albumin:creatinine ratio also appeared to be independent of concurrent SGLT2 inhibitor use (all interaction P ≥0.08). Finally, adverse events did not differ by baseline SGLT2 inhibitor use. Conclusions: The efficacy and safety of efpeglenatide appear independent of concurrent SGLT2 inhibitor use. These data support combined SGLT2 inhibitor and GLP-1 RA therapy in type 2 diabetes.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sattar, Professor Naveed
• Authors: Lam, C. S.P., Ramasundarahettige, C., Branch, K. R.H., Sattar, N., Rosenstock, J., Pratley, R., Del Prato, S., Lopes, R. D., Niemoeller, E., Khurmi, N. S., Baek, S., and Gerstein, H. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Circulation
• Publisher: American Heart Association
• ISSN: 0009-7322
• ISSN (Online): 1524-4539
• Published Online: 14 November 2021
• Copyright Holders: Copyright © 2021 American Heart Association, Inc
• First Published: First published in Circulation 145(8): 565-574
• Publisher Policy: Reproduced in accordance with the publisher copyright policy