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

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.

Comparative safety and cardiovascular effectiveness of sodium‐glucose cotransporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists in nursing homes

“…dipeptidyl peptidase-4 inhibitors). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Guidelines for the management of type 2 diabetes mellitus (T2DM) now make specific recommendations for SGLT2is or GLP-1RAs for individuals with certain conditions [i.e. cardiovascular disease, heart failure (HF), chronic kidney disease] and SGLT2is are recommended as part of guidelinedirected medical therapy for HF.…”

“…However, most studies included community-dwelling adults, and no studies had an explicit focus on nursing home (NH) residents. 1,4,7,9,15, Limited evidence from post-hoc analyses of randomized clinical trials suggests that the magnitude of benefit from SGLT2is and GLP-1RAs may differ for patients depending on their underlying diseases, severity of illness and age. 4,7,8,53 It is possible that the effectiveness and safety of these medication classes differ among NH residents.…”

“…Randomized clinical trials and observational studies have shown that SGLT2is and GLP‐1RAs reduce the risk of mortality, cardiovascular events and kidney outcomes compared with placebo or other glucose‐lowering medications (e.g. dipeptidyl peptidase‐4 inhibitors) 1–16 . Guidelines for the management of type 2 diabetes mellitus (T2DM) now make specific recommendations for SGLT2is or GLP‐1RAs for individuals with certain conditions [i.e.…”

“…Previous observational studies have compared the safety and effectiveness of SGLT2is and GLP‐1RAs. However, most studies included community‐dwelling adults, and no studies had an explicit focus on nursing home (NH) residents 1,4,7,9,15,20–52 . Limited evidence from post‐hoc analyses of randomized clinical trials suggests that the magnitude of benefit from SGLT2is and GLP‐1RAs may differ for patients depending on their underlying diseases, severity of illness and age 4,7,8,53 .…”