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

Aug 29, 2024JACC. Heart failure

Use of GLP-1 Receptor Drugs in Overweight or Obese Patients with Diabetes and Heart Failure with Preserved Pumping, Taking SGLT2 Inhibitors

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Abstract

A total of 7,044 patients were analyzed, revealing that GLP-1 RA combined with SGLT2i is associated with a significantly lower risk of heart failure exacerbations and hospitalizations.

Patients receiving both GLP-1 RA and SGLT2i showed a reduced risk of heart failure exacerbations compared to those on SGLT2i only.
There was a lower incidence of all-cause emergency department visits and hospitalizations in the combination therapy group.
New-onset atrial arrhythmias and acute kidney injury occurred less frequently in patients on GLP-1 RA plus SGLT2i.
The combination therapy was associated with a decreased risk of pulmonary hypertension.
Higher rates of diabetic retinopathy were observed in patients using both GLP-1 RA and SGLT2i compared to SGLT2i alone.

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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/m, 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. 2

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.

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

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