Sodium-glucose co-transporter-2 inhibitors in type 2 diabetes: Are clinical trial benefits for heart failure reflected in real-world clinical practice? A systematic review and meta-analysis of observational studies.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), London, UK.

Diabetes, obesity & metabolism. 2023;(2):501-515

Abstract

AIM: To determine the absolute risk reduction (ARR) of heart failure events in people treated with sodium-glucose co-transporter-2 (SGLT2) inhibitors. MATERIALS AND METHODS We searched PubMed, EMBASE, CINAHL and ISI Web of Science for observational studies published to 9 May 2022 that explored the association between SGLT2 inhibitors and any indication for heart failure (including new diagnosis or hospitalization for heart failure) in type 2 diabetes. Identified studies were independently screened by two reviewers and assessed for bias using the Newcastle-Ottawa scale. Eligible studies with comparable outcome data were pooled for meta-analysis using random-effects models, reporting hazard ratios (HRs) with 95% confidence intervals (CIs). The ARR per 100 person-years was determined overall, and in subgroups with and without baseline cardiovascular disease (CVD). RESULTS From 43 eligible studies, with a total of 4 818 242 participants from 17 countries, 21 were included for meta-analysis. SGLT2 inhibitors were associated with a reduced risk of hospitalization for heart failure (HR 0.65, 95% CI 0.59-0.72) overall and both in those with CVD (HR 0.78, 95% CI 0.68-0.89) and without CVD (HR 0.53, 95% CI 0.39-0.71). Risk reduction for hospitalization for heart failure in people with a history of CVD (ARR 1.17, 95% CI 0.78-1.55) was significantly greater than for those without CVD (ARR 0.39, 95% CI 0.32-0.47). The number-needed-to-treat to prevent one event of hospitalization for heart failure was 86 (95% CI 65-128) person-years of treatment for the CVD group and 256 (95% CI 215-316) person-years for those without CVD. CONCLUSIONS Real-world SGLT2 inhibitor use supports randomized trial data for the size effect of reduced hospitalization for heart failure in type 2 diabetes, although with a much lower ARR in people without CVD.

Methodological quality

Publication Type : Meta-Analysis

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