GLP-1 Receptor Agonists Among Patients With Overweight or Obesity, Diabetes, and HFpEF on SGLT2 Inhibitors

Rushin Patel; Mark Wadid; Bhargav Makwana; Ashish Kumar; Sumanth Khadke; Ammar Bhatti; Ahan Banker; Zaid Husami; Sherif Labib; David Venesy; Gregg Fonarow; Mikhail Kosiborod; Sadeer Al-Kindi; Deepak L Bhatt; Sourbha Dani; Anju Nohria; Javed Butler; Sarju Ganatra

doi:10.1016/j.jchf.2024.07.006

GLP-1 Receptor Agonists Among Patients With Overweight or Obesity, Diabetes, and HFpEF on SGLT2 Inhibitors

JACC Heart Fail. 2024 Aug 16:S2213-1779(24)00561-4. doi: 10.1016/j.jchf.2024.07.006. Online ahead of print.

Authors

Rushin Patel¹, Mark Wadid¹, Bhargav Makwana¹, Ashish Kumar², Sumanth Khadke¹, Ammar Bhatti¹, Ahan Banker¹, Zaid Husami¹, Sherif Labib¹, David Venesy¹, Gregg Fonarow³, Mikhail Kosiborod⁴, Sadeer Al-Kindi⁵, Deepak L Bhatt⁶, Sourbha Dani¹, Anju Nohria⁷, Javed Butler⁸, Sarju Ganatra⁹

Affiliations

¹ Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA.
² Department of Internal Medicine, Cleveland Clinic Akron General Hospital, Cleveland, Ohio, USA.
³ Ahmanson-UCLA Cardiomyopathy Center, Division of Cardiology, University of California Los Angeles, Los Angeles, California, USA.
⁴ Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.
⁵ Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Cardiovascular Center, Houston, Texas, USA.
⁶ Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁷ Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁸ Baylor Scott and White Research Institute, Dallas, Texas, USA; and iDepartment of Cardiovascular Medicine, University of Mississippi, Jackson, Mississippi, USA.
⁹ Department of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA. Electronic address: Sarju.Ganatra@Lahey.org.

PMID: 39207323
DOI: 10.1016/j.jchf.2024.07.006

Abstract

Background: Although the use of glucagon-like peptide-1 receptor agonist (GLP-1 RA) in patients with obesity and heart failure with preserved ejection fraction (HFpEF) has demonstrated improvement in cardiovascular outcomes, the incremental benefits of GLP-1 RA for patients already on sodium-glucose cotransporter 2 inhibitors (SGLT2is) remain underexplored.

Objectives: This study aimed to assess the incremental benefits of GLP-1 RA in patients with type 2 diabetes mellitus, overweight/obesity, and HFpEF receiving SGLT2i therapy.

Methods: The authors conducted a retrospective cohort study using the TriNetX research database including patients ≥18 years with type 2 diabetes mellitus, body mass index ≥27 kg/m², and HFpEF on SGLT2i. Two cohorts were created based on GLP-1 RA prescription. The outcomes were heart failure exacerbation, all-cause emergency department visits/hospitalizations among others over a 12-month period.

Results: A total of 7,044 patients remained in each cohort after propensity score matching. There was a significantly lower risk of heart failure exacerbations, all-cause emergency department visits/hospitalizations, new-onset atrial arrhythmias, new-onset acute kidney injury, and pulmonary hypertension in the GLP-1 RA plus SGLT2i cohort compared with the SGLT2i-only cohort. The associated benefits persisted across different body mass indexes and ejection fractions as well as in patients with elevated natriuretic peptide. The risk of diabetic retinopathy was higher in the combination therapy group than with SGLT2i-only use.

Conclusions: GLP-1 RA, in addition to SGLT2i, was associated with a significantly lower risk of heart failure hospitalizations in this patient population, suggesting a potential incremental benefit. This highlights the need for prospective studies to confirm the clinical benefits.

Keywords: GLP-1 receptor agonists; SGLT2is; heart failure with preserved ejection fraction; obesity; overweight.