Systematic Reviews/Meta-Analysis
Monday, November 13, 2023
01:00 PM–02:30 PM
Abstract
Background:
This network meta-analysis evaluates the long-term safety and efficacy of SGLT2 inhibitors and placebo on serious and cardiovascular adverse events from outcome trials in individuals with diabetes at high-risk for cardiovascular events.
Methods:
A comprehensive literature search was conducted in PubMed from January 2010 to December 2022 to identify randomized controlled trials with a follow-up period of two or more years. The search utilized generic terms for canagliflozin, empagliflozin, dapagliflozin, and ertugliflozin. Trials focusing on heart failure, microvascular disease, or renal disease outcomes were excluded. Outcomes of interest included serious adverse events (SAEs) and cardiovascular adverse events (combined endpoint of CV death, myocardial infarction, and stroke). Three independent evaluators assessed risk of bias using the Cochrane Risk of Bias (RoB) tool. Frequentist and Bayesian network meta-analyses were employed for pair-wise comparisons of active treatment against placebo. Surface Under the Cumulative RAnking (SUCRA) values were calculated to rank the outcomes.
Results:
Five trials involving 46,961 high-risk individuals with diabetes and minimal risk of bias were included. Canagliflozin and empagliflozin were associated with fewer SAEs compared to placebo in the frequentist analysis but not in Bayesian analysis. Canagliflozin and empagliflozin had the highest probability of success (fewer SAEs compared to placebo) according to weighted SUCRA rankings. Similar findings were observed for cardiovascular events, with canagliflozin and empagliflozin showing a significant reduction in events compared to placebo in the frequentist analysis and not replicated in Bayesian analysis. Canagliflozin and empagliflozin had the highest probability of success (fewer SAEs and cardiovascular outcomes compared to placebo) based on the weighted SUCRA rankings.
Discussion:
Canagliflozin and empagliflozin were similarly ranked better than placebo in respect to SAEs and cardiovascular events in frequentist but not Bayesian analysis. High-risk patients may benefit from canagliflozin or empagliflozin treatment.
Other:
This work was unfunded, non-registered and the authors have no potential conflicts of interest.
Presenting Author
Matthew Silva PharmDMCPHS
Authors
Dhaval Mandli PharmD
MCPHS
Rachna Sharma PharmD
MCPHS