1. Effects of exenatide and open-label SGLT2 inhibitor treatment, given in parallel or sequentially, on mortality and cardiovascular and renal outcomes in type 2 diabetes: insights from the EXSCEL trial
- Author
-
Robert C. Penland, Marcus Thuresson, Robert J. Mentz, James Ruggles, C. David Sjöström, Adrian F. Hernandez, Srinivas Bachina, John B. Buse, Lindsay E. Clegg, Stephanie M. Gustavson, David W. Boulton, Hiddo J.L. Heerspink, Rury R. Holman, Groningen Kidney Center (GKC), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
- Subjects
Male ,eGFR slope ,lcsh:Diseases of the circulatory (Cardiovascular) system ,Time Factors ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Kidney ,THERAPY ,DOUBLE-BLIND ,0302 clinical medicine ,Risk Factors ,Cause of Death ,Multicenter Studies as Topic ,Medicine ,Original Investigation ,Randomized Controlled Trials as Topic ,Hazard ratio ,SGLT2 inhibitor ,Middle Aged ,Treatment Outcome ,Cardiovascular Diseases ,Drug Therapy, Combination ,Female ,Cardiology and Cardiovascular Medicine ,Glomerular Filtration Rate ,medicine.drug ,medicine.medical_specialty ,Cardiovascular outcomes ,GLP-1 receptor agonist ,030209 endocrinology & metabolism ,Placebo ,Incretins ,Risk Assessment ,Drug Administration Schedule ,03 medical and health sciences ,Propensity score matching ,Diabetes mellitus ,Internal medicine ,Post-hoc analysis ,Type 2 diabetes mellitus ,Humans ,COTRANSPORTER 2 INHIBITORS ,Combination therapy ,Sodium-Glucose Transporter 2 Inhibitors ,Aged ,business.industry ,Proportional hazards model ,medicine.disease ,Diabetes Mellitus, Type 2 ,lcsh:RC666-701 ,PEPTIDE-1 RECEPTOR AGONISTS ,Exenatide ,business ,Mace - Abstract
Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve cardiovascular and renal outcomes in patients with type 2 diabetes through distinct mechanisms. However, evidence on clinical outcomes in patients treated with both GLP-1 RA and SGLT2i is lacking. We aim to provide insight into the effects of open-label SGLT2i use in parallel with or shortly after once-weekly GLP-1 RA exenatide (EQW) on cardiorenal outcomes. Methods In the EXSCEL cardiovascular outcomes trial EQW arm, SGLT2i drop-in occurred in 8.7% of participants. These EQW+SGLT2i users were propensity-matched to: (1) placebo-arm participants not taking SGLT2i (n = 572 per group); and to (2) EQW-arm participants not taking SGLT2i (n = 575), based on their last measured characteristics before SGLT2i initiation, and equivalent study visit in comparator groups. Time-to-first major adverse cardiovascular event (MACE) and all-cause mortality (ACM) were compared using Cox regression analyses. eGFR slopes were quantified using mixed model repeated measurement analyses. Results In adjusted analyses, the risk for MACE with combination EQW+SGLT2i use was numerically lower compared with both placebo (adjusted hazard ratio 0.68, 95% CI 0.39–1.17) and EQW alone (0.85, 0.48–1.49). Risk of ACM was nominally significantly reduced compared with placebo (0.38, 0.16–0.90) and compared with EQW (0.41, 0.17–0.95). Combination EQW+SGLT2i use also nominally significantly improved estimated eGFR slope compared with placebo (+ 1.94, 95% CI 0.94–2.94 mL/min/1.73 m2/year) and EQW alone (+ 2.38, 1.40–3.35 mL/min/1.73 m2/year). Conclusions This post hoc analysis supports the hypothesis that combinatorial EQW and SGLT2i therapy may provide benefit on cardiovascular outcomes and mortality. Trial registration Clinicaltrials.gov, Identifying number: NCT01144338, Date of registration: June 15, 2010.
- Published
- 2019
- Full Text
- View/download PDF