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Efpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O Trial.

Publication ,  Journal Article
Lam, CSP; Ramasundarahettige, C; Branch, KRH; Sattar, N; Rosenstock, J; Pratley, R; Del Prato, S; Lopes, RD; Niemoeller, E; Khurmi, NS; Baek, S ...
Published in: Circulation
February 22, 2022

BACKGROUND: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists reduce cardiovascular events among patients with type 2 diabetes. However, no cardiovascular outcome trial has evaluated the long-term effects of their combined use. The AMPLITUDE-O trial (Effect of Efpeglenatide on Cardiovascular Outcomes) reported that once-weekly injections of the glucagon-like peptide-1 receptor agonists efpeglenatide (versus placebo) reduced major adverse cardiovascular events (MACEs); MACEs, coronary revascularization, or unstable angina hospitalization (expanded MACEs); a renal composite outcome; and MACEs or death in people with type 2 diabetes and cardiovascular 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 glucagon-like peptide-1 receptor agonist cardiovascular 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 with Cox proportional hazards models adjusted for region, SGLT2 inhibitor randomization strata, and the SGLT2 inhibitor-by-treatment interaction. Continuous variables were analyzed with a mixed-effects models for repeated measures that also included an interaction term. RESULTS: The effect (hazard ratio [95% CI]) of efpeglenatide versus placebo in the absence and presence of baseline SGLT2 inhibitors on MACEs (0.74 [0.58-0.94] and 0.70 [0.37-1.30], respectively), expanded MACEs (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 MACEs 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). The reduction of blood pressure, body weight, low-density lipoprotein cholesterol, and urinary albumin-to-creatinine ratio by efpeglenatide also appeared to be independent of concurrent SGLT2 inhibitor use (all interaction P≥0.08). Last, adverse events did not differ by baseline SGLT2 inhibitor use. CONCLUSIONS: The efficacy and safety of efpeglenatide appear to be independent of concurrent SGLT2 inhibitor use. These data support combined SGLT2 inhibitor and glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03496298.

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Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

February 22, 2022

Volume

145

Issue

8

Start / End Page

565 / 574

Location

United States

Related Subject Headings

  • Sodium-Glucose Transporter 2 Inhibitors
  • Sodium-Glucose Transporter 2
  • Proline
  • Middle Aged
  • Male
  • Hypoglycemic Agents
  • Humans
  • Female
  • Diabetes Mellitus, Type 2
  • Cardiovascular System & Hematology
 

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Lam, C. S. P., Ramasundarahettige, C., Branch, K. R. H., Sattar, N., Rosenstock, J., Pratley, R., … Gerstein, H. C. (2022). Efpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O Trial. Circulation, 145(8), 565–574. https://doi.org/10.1161/CIRCULATIONAHA.121.057934
Lam, Carolyn S. P., Chinthanie Ramasundarahettige, Kelley R. H. Branch, Naveed Sattar, Julio Rosenstock, Richard Pratley, Stefano Del Prato, et al. “Efpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O Trial.Circulation 145, no. 8 (February 22, 2022): 565–74. https://doi.org/10.1161/CIRCULATIONAHA.121.057934.
Lam CSP, Ramasundarahettige C, Branch KRH, Sattar N, Rosenstock J, Pratley R, et al. Efpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O Trial. Circulation. 2022 Feb 22;145(8):565–74.
Lam, Carolyn S. P., et al. “Efpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O Trial.Circulation, vol. 145, no. 8, Feb. 2022, pp. 565–74. Pubmed, doi:10.1161/CIRCULATIONAHA.121.057934.
Lam CSP, Ramasundarahettige C, Branch KRH, Sattar N, Rosenstock J, Pratley R, Del Prato S, Lopes RD, Niemoeller E, Khurmi NS, Baek S, Gerstein HC. Efpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O Trial. Circulation. 2022 Feb 22;145(8):565–574.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

February 22, 2022

Volume

145

Issue

8

Start / End Page

565 / 574

Location

United States

Related Subject Headings

  • Sodium-Glucose Transporter 2 Inhibitors
  • Sodium-Glucose Transporter 2
  • Proline
  • Middle Aged
  • Male
  • Hypoglycemic Agents
  • Humans
  • Female
  • Diabetes Mellitus, Type 2
  • Cardiovascular System & Hematology