GLP-1 Receptor Agonists Along With SGLT2 Inhibitors for HFpEF
Quick Takes
- Patients with overweight or obesity, diabetes, and HFpEF prescribed SGLT2 inhibitors experienced reduced risk of HF exacerbations, hospitalizations, and ED visits with addition of GLP-1 RA.
- This was the largest trial to date of adding GLP-1 RA therapy for patients prescribed SGLT2 inhibitors with BMI ≥27 kg/m2, diabetes, and HFpEF suggesting incremental benefit on a variety of clinical outcomes.
Study Questions:
What is the incremental benefit in patients with heart failure and preserved ejection fraction (HFpEF) of glucagon-like peptide-1 receptor agonists (GLP-1 RA) combined with sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) and body mass index (BMI) ≥27 kg/m2?
Methods:
This was a retrospective, observational cohort study of 29,922 patients ≥18 years old, diagnosed with T2DM, BMI of ≥27 kg/m2, and documented history of HFpEF (left ventricular EF [LVEF] ≥45%) who were prescribed an SGLT2i using data from the TriNetX Global Research Network. Comparison groups were patients receiving both GLP-1 RA and SGLT2i (n = 7,044) and those receiving SGLT2i alone (n = 7,044) within 12 months of diagnosis of HFpEF after propensity-score matching. Subgroups based on BMI, B-type natriuretic peptide (BNP)/N-terminal pro-BNP (NT-proBNP), and LVEF were evaluated. Outcomes over a 12-month follow-up included: HF exacerbations, all-cause hospitalizations or emergency department (ED) visits, all-cause mortality, new-onset atrial fibrillation/atrial flutter (AF/AFL), pulmonary hypertension, C-reactive protein (CRP) levels ≥5 mg/dL, acute kidney injury (AKI), and new-onset renal replacement therapy.
Results:
Baseline characteristics were well matched after propensity-score matching for demographics, comorbidities, medication use at baseline, and laboratory values. The GLP-1 RA and SGLT2i cohort experienced lower risk over the 12-month follow-up period of HF exacerbations (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.58-0.67), all-cause hospitalizations or ED visits (HR, 0.74; 95% CI, 0.71-0.78), all-cause mortality (HR, 0.64; 95% CI, 0.54-0.75), new-onset AF/AFL, pulmonary hypertension, CRP levels ≥5 mg/dL, AKI, and new-onset renal replacement therapy within a 12-month follow-up period compared to patients receiving SGLT2i alone. Addition of GLP-1 RA was associated across all subgroups of LVEF, BMI, and BNP/NT-proBNP with lower risk of HF exacerbation and all-cause ED visits or hospitalizations, and in the BMI and BNP/NT-proBNP subgroups for AKI. Safety outcomes were similar between cohorts, except a higher risk of diabetic retinopathy in the combination GLP-1 RA and SGLT2i cohort (HR, 1.36; 95% CI, 1.215-1.516).
Conclusions:
The authors report that patients with HFpEF with overweight/obesity with T2DM on an SGLT2i experienced a lower rate of adverse cardiovascular outcomes, including HF exacerbations, with the addition of a GLP-1 RA.
Perspective:
Clinical outcomes trials have been eagerly awaited after the STEP-HFpEF trial suggested addition of GLP-1 RA may improve quality-of-life outcomes for patients with overweight/obesity and HFpEF. The 2022 American College of Cardiology/American Heart Association guideline provides a Class 2a recommendation for SGLT2i for patients with HFpEF and HF with mid-range EF. Only a small portion of the study population was concomitantly prescribed SGLT2i in the STEP-HFpEF (3.6%) and STEP-HFpEF DM (32.8%) trials, leading to questions of whether additional benefit would remain in patients optimized on SGLT2i therapy. This trial suggests incremental benefit of GLP-1 RA addition in patients with overweight or obesity, diabetes, and HFpEF who are also prescribed SGLT2i in reducing the rates of clinical outcomes such as HF exacerbations, hospitalizations, and ED visits, among others.
Clinical Topics: Cardiovascular Care Team, Heart Failure and Cardiac Biomarkers, Prevention
Keywords: Cardiometabolic Risk Factors, Glucagon-Like Peptide-1 Receptor, Heart Failure, Preserved Ejection Fraction, Sodium-Glucose Transporter 2 Inhibitors
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