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

TY - JOUR

T1 - Primary Prevention of Cardiovascular and Heart Failure Events With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Their Combination in Type 2 Diabetes

AU - Wright, Alison K

AU - Carr, Matthew J

AU - Kontopantelis, Evangelos

AU - Leelarathna, Lalantha

AU - Thabit, Hood

AU - Emsley, Richard

AU - Buchan, Iain

AU - Mamas, Mamas A

AU - van Staa, Tjeerd P

AU - Sattar, Naveed

AU - Ashcroft, Darren M

AU - Rutter, Martin K

N1 - Funding Information: was funded by Diabetes UK (BDA: 14/0004971). We also acknowledge financial support from Medical Research Council Health eResearch Centre grant MR/K006665/1 and methodology award MR/T025085/1. M.J.C. and D.M.A. are funded by the National Institute for Health Research Greater Manchester Patient Safety Translational Research Centre (award PSTRC-2016-003). D.M.A. reports research funding from AbbVie, Almirall, Celgene, Eli Lilly, Janssen, Novartis, Union Chimique Belge (UCB), and the LEO Foundation outside the submitted work. M.K.R. has received nonpromotional speaker fees from Novo Nordisk and consultancy fees from Cell Catapult and Roche Diabetes Care and reports a modest owning of shares in GlaxoS-mithKline outside the submitted work. I.B. reports grants from the National Institute for Health Research during the conduct of the study and personal fees from AstraZeneca (chief data scientist advisor) outside the submitted work. N.S. reports grants and personal fees from Boehringer Ingelheim and personal fees from Amgen (advisory board and speaker honoraria), AstraZeneca (advisory board and speaker honoraria), Eli Lilly (advisory board and speaker honoraria), Merck Sharp & Dohme (advisory board), Novartis (advisory board), Novo Nordisk (advisory board and speaker honoraria), Pfizer (advisory board), and Sanofi (advisory board and speaker honoraria) outside the submitted work. No other potential conflicts of interest relevant to this article were reported. Publisher Copyright: © 2022 by the American Diabetes Association.

PY - 2022/4/1

Y1 - 2022/4/1

N2 - OBJECTIVE: 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.

AB - OBJECTIVE: 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.

UR - http://www.scopus.com/inward/record.url?scp=85127317713&partnerID=8YFLogxK

U2 - 10.2337/dc21-1113

DO - 10.2337/dc21-1113

M3 - Article

C2 - 35100355

SN - 0149-5992

VL - 45

SP - 909

EP - 918

JO - Diabetes Care

JF - Diabetes Care

IS - 4

ER -