Systematic Reviews/Meta-Analysis
Sunday, November 12, 2023
12:45 PM–02:15 PM
Abstract
Background:
Sodium-glucose co-transporter 2 inhibitors (SGLT2I), glucagon-like peptide-1 receptor agonists (GLP-1RA), and finerenone have shown renoprotective effects in patients with diabetic kidney disease (DKD). However, the combination effects of these agents have not been established. This network meta-analysis (NMA) was to compare the effects of combination therapy using these agents with monotherapy in DKD patients.
Methods:
PubMed, EMBASE, and CENTRAL were searched up to May 1, 2023 to identify randomized controlled trials comparing the kidney outcomes of SGLT2I, GLP1RA, or finerenone as mono- or combined therapy with placebo in DKD patients. Therapy with finerenone+SGLT2I, finerenone+GLP1RA, SGLT2I, GLP1RA, finerenone, and placebo were analyzed. Trial quality was assessed using Cochrane risk-of-bias tool. Primary outcomes were kidney composite outcome and discontinuation due to adverse effects (AE). Secondary outcomes were urinary-albumin-creatinine ratio change, glomerular filtration rate slope, and safety outcomes. Frequentist NMA was performed and therapies were ranked with P-score.
Results:
A total of twenty-four trials (n=51,508) were included. From 19 trials (n=34,402), finerenone+SGLT2I was more effective to reduce the risk of kidney composite outcome than SGLT2I (hazard ratio [HR] 0.42; 95% confidence interval [CI] 0.14–1.26), finerenone+GLP1RA (HR 0.39; 95% CI 0.11–1.43), finerenone (HR 0.35, 95% CI 0.11–1.05), GLP1RA (HR 0.32, 95% CI 0.11–0.99), or placebo (HR 0.27, 95% CI 0.09–0.82) (in P-score order). Discontinuation due to AE was fewer with finerenone+SGLT2I than SGLT2I (odds ratio [OR] 0.78, 95% CI 0.41–1.46), placebo (OR 0.74, 95% CI 0.39–1.42), finerenone (OR 0.62, 95% CI 0.32–1.20), GLP1RA (OR 0.17, 95% CI 0.07–0.42), or finerenone+GLP1RA (OR 0.14, 95% CI 0.05–0.40) (in P-score order).
Discussion:
In this NMA, finerenone+SGLT2I therapy was better to reduce the risk of kidney events and better tolerated than monotherapy or finerenone+GLP1RA in DKD patients. However, due to a limited number of finerenone trials included, further studies are warranted.
Other:
No funding/conflicts of interest. Registered at PROSPERO (CRD42023382484).
Presenting Author
Susan Lewis PharmDUniversity of Findlay College of Pharmacy
Authors
Mi Sung Kim BS
Ewha Woman's University, Graduate School of Pharmaceutical Sciences, Seoul, Republic of Korea.
Myeong Gyu Kim Ph.D.
Ewha Womans University
Soo Min Jang PharmD
Loma Linda University School of Pharmacy
Sandy (Jeong Yeon) Rhie PharmD, PhD
Ewha Womans University