Primary Prevention of Cardiovascular and Heart Failure Events With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Their Combination in Type 2 Diabetes

Abstract

OBJECTIVES To assess associations between current use of sodium–glucose cotransporter 2 inhibitors (SGLT2is), glucagon-like peptide 1 receptor agonists (GLP-1RAs), and their combination and risk for major adverse cardiac and cerebrovascular events (MACCE) and heart failure (HF) in people with type 2 diabetes. RESEARCH DESIGN AND METHODS In three nested case-control studies involving patients with type 2 diabetes in England and Wales (primary care data from the Clinical Practice Research Datalink and Secure Anonymised Information Linkage Databank with linkage to hospital and mortality records), we matched each patient experiencing an event with up to 20 control subjects. Adjusted odds ratios (ORs) for MACCE and HF among patients receiving SGLT2i or GLP-1RA regimens versus other combinations were estimated using conditional logistic regression and pooled using random-effects meta-analysis. RESULTS Among 336,334 people with type 2 diabetes and without cardiovascular disease, 18,531 (5.5%) experienced a MACCE. In a cohort of 411,206 with type 2 diabetes and without HF, 17,451 (4.2%) experienced an HF event. Compared with other combination regimens, the adjusted pooled OR and 95% CI for MACCE associated with SGLT2i regimens was 0.82 (0.73, 0.92), with GLP-1RA regimens 0.93 (0.81, 1.06), and with the SGLT2i/GLP-1RA combination 0.70 (0.50, 0.98). Corresponding data for HF were SGLT2i 0.49 (0.42, 0.58), GLP-1RA 0.82 (0.71, 0.95), and SGLT2i/GLP-1RA combination 0.43 (0.28, 0.64). CONCLUSIONS SGLT2i and SGLT2i/GLP-1RA combination regimens may be beneficial in primary prevention of MACCE and HF and GLP-1RA for HF. These data call for primary prevention trials using these agents and their combination.

Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study (Diabetes Metab J 2022;46: 658-62)

“…Last, Dr. Kawada proposed a discussion regarding the cardiovascular benefits of the combination of SGLT2 inhibitor and GLP-1 receptor agonist. We agree that these two drug classes, both individually and combined, are effective in reducing the risk of cardiovascular disease and death by different mechanisms [2][3][4]. However, this aspect is out of the scope of this study, as the primary outcome of our study was the efficacy of the combination therapy in terms of glycemic control for at Response https://doi.org/10.4093/dmj.2022.0166 pISSN 2233-6079 • eISSN 2233-6087 Diabetes Metab J 2022;46:665-666 Diabetes Metab J 2022;46:665-666 https://e-dmj.org least 1 year.…”

Learning by reading: A review of recent diabetes articles

“…Another study of the dataset found 18.1 and 13.9 major adverse cardiovascular events (MACE) and HF events per 1000 person‐years of follow‐up among persons with T2D not having prior cardiovascular disease or prior HF, respectively; 2‐3% of persons in the data set used SGLT2i and glucagon‐like peptide 1 receptor agonists (GLP‐1RA), and 0.2‐0.3% used both. Use of SGLT2i, GLP‐1RA, and their combination was associated with 18%, 7%, and 30% lower odds of MACE, and with 51%, 18%, and 43% lower odds of HF events, respectively 11 …”

“…Use of SGLT2i, GLP-1RA, and their combination was associated with 18%, 7%, and 30% lower odds of MACE, and with 51%, 18%, and 43% lower odds of HF events, respectively. 11 In a propensity score matched analysis of GLP-1RA use in the Taiwan National Health Insurance Research Database of >4 million persons with T2D from 1998 to 2018, the average compliance rate was 40% overall, but 65% for those with >251 days of GLP-1RA use; the hazard rate for stroke was 1.03, 0.83, 0.69, and 0.25 for those with 1-59, 60-153, 154-251, and >251 days of GLP-1RA use, respectively, 12 confirming randomized controlled trial evidence of benefit of these agents. Another analysis from Taiwan compared persons with T2D initiating glyburide or glipizide, which block cardiac mitochondrial ATP-sensitive potassium channels, with those initiating gliclazide or glimepiride, not having this effect, from 2007 to 2016; the former agents were associated with 1.2-fold greater risk of MACE than the latter, with 1.2-fold greater risk of stroke and 2.6-fold greater risk of cardiovascular death, with significant 4.7-fold increase in MACE risk appearing during the first 90 days of use of the agents.…”

“…Use of SGLT2i, GLP‐1RA, and their combination was associated with 18%, 7%, and 30% lower odds of MACE, and with 51%, 18%, and 43% lower odds of HF events, respectively. 11 …”

Microstructure: a potential path to elucidate sex-specific pathological mechanisms in heart failure?

“…Until recently, the options for the very early prevention of HF were very limited, without significant improvement in cardiovascular outcomes. However, the enthusiasm for the primary prevention of HF visibly increased in recent years following the encouraging and clinically significant results established by SGLT2 inhibitor trials in patients with diabetes without HF 9. Nevertheless, further research is necessary to identify additional effective pathways to prevent HF in all comers, and non-invasive characterisation of myocardial microstructure could help target patients at increased risk of incident HF.…”