SAN FRANCISCO — Combination treatment of a sodium-glucose cotransporter 2 (SGLT2) inhibitor with exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, may protect renal function and reduce all-cause mortality risk in patients with type 2 diabetes, according to a post-hoc analysis from the EXSCEL study (Exenatide Study of Cardiovascular Event Lowering Trial; ClinicalTrials.gov Identifier: NCT01144338) presented at the American Diabetes Association 79th Scientific Sessions, held June 7 to 11, 2019.
Previous studies have shown that both SGLT2 inhibitors and GLP-1 receptor agonists may improve cardiovascular and renal outcomes. In this analysis, the researchers aimed to assess these outcomes in patients receiving a combination of exenatide and SGLT2 inhibitor, as approximately 10% of the participants in the EXSCEL study were using this combination.
The investigators propensity-matched patients receiving the combination of SGLT2 inhibitor with exenatide to 575 patients receiving exenatide but not SGLT2 inhibitor and 572 patients receiving placebo and no SGLT2 inhibitor. They compared major adverse cardiovascular events and all-cause mortality between the study groups, and also looked at changes in estimated glomerular filtration rate (eGFR).
While combination of SGLT2 inhibitor with exenatide numerically reduced the risk for major adverse cardiovascular events compared with exenatide only (incidence rate of 3.27 vs 4.38 events/100 participants-years) and placebo (3.29 vs 4.81 events/100 participants-years), the adjusted hazard ratios were not significantly different.
The all-cause mortality risk was significantly reduced with the combination of SGLT2 inhibitor and exenatide compared with exenatide only (0.99 vs 2.96 events/100 participants-years; adjusted hazard ratio, 0.41, 95% CI, 0.17-0.95) and compared with placebo (1.00 vs 2.71 events/100 participants-years; adjusted hazard ratio, 0.38, 95% CI, 0.16-0.90).
The combination therapy also significantly improved eGFR slope compared with exenatide only (eGFR slope, +1.27 vs -1.11, respectively; P <.001) and placebo (eGFR slope, +1.21 vs -0.71; respectively, P <.001).
“This post hoc analysis offers support for the hypothesis that combinatorial exenatide and [SGLT2 inhibitor] use may provide benefit on renal function and all-cause mortality,” concluded the researchers.
Multiple authors declared associations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Clegg LE, Penland RC, Boulton DW, et al. Effect of open-label SGLT inhibitor treatment when combined with exenatide on cardiovascular and renal outcomes in EXSCEL. Presented at: American Diabetes Association 79th Scientific Sessions; June 7-11, 2019; San Francisco, CA. Poster 6-LB.