Cardiovascular diabetologyAug 31, 2024

Comparing diabetes drugs' effects on heart failure with normal pumping strength

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Mar 28, 2026

Abstract

3,428 patients were analyzed, showing that both GLP1-RA and SGLT2 inhibitors significantly improved left ventricular ejection fraction (LVEF) compared to placebo.

GLP1-RA treatment resulted in a mean difference of 2.8% in LVEF, while SGLT2 inhibitors showed a mean difference of 3.2%.
SGLT2 inhibitors significantly reduced myocardial fibrosis by 3.5%, compared to a reduction of 2.3% with GLP1-RA.
Both GLP1-RA and SGLT2 inhibitors improved functional capacity, with increases of 45 meters and 50 meters, respectively, in the 6-minute walk test.
Secondary outcomes indicated significant reductions in HbA1c levels, with a mean difference of -1.1% for GLP1-RA and -1.0% for SGLT2 inhibitors.
Weight loss was observed with both treatments, averaging -2.5 kg for GLP1-RA and -2.0 kg for SGLT2 inhibitors.
Both therapies led to significant decreases in systolic blood pressure, with GLP1-RA reducing it by -5.2 mmHg and SGLT2 inhibitors by -4.8 mmHg.

Simplified

BACKGROUND: (HFpEF) is common in type 2 diabetes mellitus (T2D), leading to high morbidity and mortality. Managing HFpEF in diabetic patients is challenging with limited treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and (GLP1-RA) have shown potential cardiovascular benefits. This meta-analysis compares the effects of GLP1-RA and SGLT2 inhibitors on HFpEF in T2D patients.

METHODS: We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating GLP1-RA and SGLT2 inhibitors' impact on HFpEF in T2D patients. Databases searched included PubMed, MEDLINE, and Cochrane Library up to July 2024. Primary outcomes were changes in left ventricular ejection fraction (LVEF), myocardial fibrosis (extracellular volume fraction, ECV), and functional capacity (6-minute walk test, 6MWT). Secondary outcomes included HbA1c, body weight, and systolic blood pressure (SBP). RESULTS: Twelve studies with 3,428 patients (GLP1-RA: 1,654; SGLT2 inhibitors: 1,774) were included. Both GLP1-RA and SGLT2 inhibitors significantly improved LVEF compared to placebo (GLP1-RA: mean difference [MD] 2.8%, 95% confidence interval [CI] 1.5 to 4.1, p < 0.001; SGLT2 inhibitors: MD 3.2%, 95% CI 2.0 to 4.4, p < 0.001). SGLT2 inhibitors significantly reduced myocardial fibrosis (MD -3.5%, 95% CI -4.2 to -2.8, p < 0.001) more than GLP1-RA (MD -2.3%, 95% CI -3.0 to -1.6, p < 0.001). Functional capacity improved significantly with both treatments (GLP1-RA: MD 45 m, 95% CI 30 to 60, p < 0.001; SGLT2 inhibitors: MD 50 m, 95% CI 35 to 65, p < 0.001). Secondary outcomes showed reductions in HbA1c (GLP1-RA: MD -1.1%, 95% CI -1.4 to -0.8, p < 0.001; SGLT2 inhibitors: MD -1.0%, 95% CI -1.3 to -0.7, p < 0.001) and body weight (GLP1-RA: MD -2.5 kg, 95% CI -3.1 to -1.9, p < 0.001; SGLT2 inhibitors: MD -2.0 kg, 95% CI -2.6 to -1.4, p < 0.001). Both treatments significantly lowered SBP (GLP1-RA: MD -5.2 mmHg, 95% CI -6.5 to -3.9, p < 0.001; SGLT2 inhibitors: MD -4.8 mmHg, 95% CI -6.0 to -3.6, p < 0.001).

CONCLUSIONS: GLP1-RA and SGLT2 inhibitors significantly benefit HFpEF management in T2D patients. SGLT2 inhibitors reduce myocardial fibrosis more effectively, while both improve LVEF, functional capacity, and metabolic parameters. These therapies should be integral to HFpEF management in diabetic patients. Further research is needed on long-term outcomes and potential combined therapy effects.

Key numbers

3.2%

Improvement in LVEF by SGLT2 inhibitors

Mean difference in left ventricular ejection fraction compared to placebo

3.5%

Reduction in myocardial fibrosis by SGLT2 inhibitors

Mean difference in extracellular volume fraction compared to GLP1-RA

50 m

Improvement in functional capacity by SGLT2 inhibitors

Mean difference in 6-minute walk test compared to baseline

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Comparing diabetes drugs' effects on heart failure with normal pumping strength

Abstract

Key numbers

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