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

Cardiovascular Diabetology

卷:18

Stephanie Gustavson¹  C. David Sjöström¹  James A. Ruggles²  Robert C. Penland³  Lindsay E. Clegg³  Srinivas Bachina³  David W. Boulton³  Hiddo J. L. Heerspink⁴  Rury R. Holman⁵  Robert J. Mentz⁶  Adrian F. Hernandez⁶  Marcus Thuresson⁷  John B. Buse⁸ 

[1] BioPharmaceuticals R&D, AstraZeneca;

[2] BioPharmaceuticals, AstraZeneca;

[3] Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca;

[4] Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen;

[5] Diabetes Trials Unit, University of Oxford;

[6] Duke University and Duke Clinical Research Institute, Duke University School of Medicine;

[7] Statisticon AB;

[8] University of North Carolina School of Medicine;

关键词: SGLT2 inhibitor;    GLP-1 receptor agonist;    Exenatide;    Cardiovascular outcomes;    eGFR slope;    Type 2 diabetes mellitus;   

DOI  :  10.1186/s12933-019-0942-x

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown