GLP1 receptor agonist with add-on SGLT2 inhibitor therapy is associated with lower risks of major adverse cardiovascular events: a population-based and machine learning causal inference analysis

Zhiyao Luo; Oscar Chou; Zita Ng; Chung Cheuk To; Jeffrey Chan; Raymond Chan; Lei Lu; Tingting Zhu; Quinncy Lee; Carmel McCEniery; Ian Wilkinson; Gregory Lip; Bernard Cheung; Gary Tse; Jiandong Zhou

doi:10.1530/endoabs.109.P110

P110

Prev Next

Section Contents Cite

Endocrine Abstracts (2025) 109 P110 | DOI: 10.1530/endoabs.109.P110

SFEBES2025 Poster Presentations Metabolism, Obesity and Diabetes (68 abstracts)

GLP1 receptor agonist with add-on SGLT2 inhibitor therapy is associated with lower risks of major adverse cardiovascular events: a population-based and machine learning causal inference analysis

Zhiyao Luo ¹ , Oscar Chou ² , Zita Ng ² , Cheuk To Chung ³ , Jeffrey Chan ⁴ , Raymond Chan ⁴ , Lei Lu ¹ , Tingting Zhu ¹ , Quinncy Lee ⁴ , Carmel McCEniery ⁵ , Ian Wilkinson ⁵ , Gregory Lip ⁶ , Bernard Cheung ² , Gary Tse ⁷ & Jiandong Zhou ²

Author affiliations

¹University of Oxford, Oxford, United Kingdom; ²University of Hong Kong, Hong Kong, China; ³Chinese University of Hong Kong, Hong Kong, China; ⁴PowerHealth Research Institute, Hong Kong, China; ⁵University of Cambridge, Cambridge, United Kingdom; ⁶University of Liverpool, Liverpool, United Kingdom; ⁷Hong Kong Metropolitan University, Hong Kong, China

Background: Both GLP-1 receptor agonists (GLP1a) and sodium-glucose cotransporter-2 (SGLT2) inhibitors confer benefits against cardiovascular diseases in type 2 diabetes mellitus (T2DM). However, the effects of SGLT2I add-on therapy amongst patients already on GLP1a users remain unknown.

Objective: This real-world study compared the risks of cardiovascular diseases in GLP1a users with or without SGLT2I add-on therapy.

Methods: This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus (T2DM) on GLP1a between 1st January 2015 and 31st December 2020 using a territory-wide registry from Hong Kong. The primary outcomes were new-onset myocardial infarction, atrial fibrillation, heart failure, and stroke/transient ischaemic attack (TIA). The secondary outcome was all-cause mortality. Propensity score matching (1:2 ratio) using the nearest neighbour search was performed. Multivariable Cox regression was used to identify significant associations. The machine learning causal inference analysis was used to estimate the treatment effects.

Results: This cohort included 2526 T2DM patients on GLP1a (median age: 52.5 years old [SD: 10.9]; 57.34 % males). The SGLT2I users and non-SGLT2I users consisted of 1968 patients and 558 patients, respectively. After matching, non-SGLT2I users were associated with high risks of myocardial infarction (Hazard ratio [HR]: 2.91; 95% Confidence Interval [CI]: 1.30-6.59) and heart failure (HR: 2.49; 95% CI: 1.22-5.08) compared to non-SGLT2I users after adjusting for demographics, comorbidities, medications, renal function, and glycaemic tests. However, non-SGLT2I users were not associated with the risks of atrial fibrillation (HR: 1.52; 95% CI: 0.65-3.53) and stroke/TIA (HR: 1.72; 95% CI: 0.70-4.24). The results remained consistent in the competing risk and the sensitivity analyses.

Conclusions: GLP1Ra with SGLT2I add-on therapy is associated with lower risks of MACE, myocardial infarction and heart failure. The results remained consistent in the machine learning causal inference analysis.