Potential unrealized mortality benefit of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transport-2 inhibitors: A report from the Veterans Health Administration Clinical Assessment, Reporting and Tracking program

Diabetes Obes Metab. 2021 Jan;23(1):97-105. doi: 10.1111/dom.14193. Epub 2020 Oct 3.

Abstract

Aim: To assess the unrealized potential of glucagon-like peptide-1 receptor agonist (GLP-1RA) or sodium-glucose co-transport-2 inhibitor (SGLT2i) use to reduce mortality in veterans with type 2 diabetes (T2D), coronary artery disease (CAD), and other characteristics congruent with clinical trial cohorts that established the efficacy of these agents.

Methods: Veterans with T2D and CAD on angiography in 2014 who were untreated with either a GLP-1RA or a SGLT2i were assessed for key eligibility criteria of the LEADER (GLP-1RA) and EMPA-REG OUTCOME (SGLT2i) trials. Trial hazard ratios and 95% confidence intervals for all-cause death were applied to deaths observed in veterans through 2018 to estimate the potential benefit of GLP-1RA or SGLT2i use.

Results: Median observation was 4.3 years. Of 15 987 veterans with T2D and CAD, 1186 (7.4%) were excluded for GLP-1RA or SGLT2i treatment, and 1386 lacked glycated haemoglobin measurement. Of the remaining 13 415 patients, 4103 (30.1%) and 5313 (39.6%) fulfilled the key criteria for the LEADER and EMPA-REG OUTCOME trials, respectively. Death occurred in 1009 (24.6%) of LEADER-eligible patients and 1335 (25.1%) of EMPA-REG OUTCOME-eligible patients. Under treatment with liraglutide in LEADER-eligible veterans, a 3.5% (0.7%-6.2%) potential absolute mortality reduction, corresponding to 144 (28-253) fewer deaths (0.88 [0.17-1.56] per 100 person-years), might have been expected. Similarly, under treatment with empagliflozin in EMPA-REG OUTCOME-eligible veterans, a 7.9% (4.5%-10.8%) potential absolute mortality reduction, corresponding to 418 (230-573) fewer deaths (1.98 [1.14-2.72] per 100 person-years), might have been expected.

Conclusions: This analysis indicates unrealized opportunities to reduce mortality in selected veterans with T2D and CAD via increased GLP-1RA and SGLT2i use.

Keywords: cardiovascular disease; empagliflozin; GLP-1; liraglutide; SGLT2 inhibitor; type 2 diabetes.

MeSH terms

  • Cardiovascular Diseases*
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucagon-Like Peptide-1 Receptor
  • Glucose
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Sodium
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Veterans Health

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sodium
  • Glucose