What is the clinical evidence from this study?

Study design: Cohort. Population: Type 2 diabetes with heart failure (HFrEF and HFpEF) (n=47379). Intervention: SGLT2 inhibitors vs. DPP4 inhibitors and GLP-1 receptor agonists. Primary outcome: Hospitalization for heart failure (HFrEF cohort, SGLT2i vs DPP4i) (HR 0.67, 95% CI 0.63, 0.72).

March 10, 2023Open Access

Cardiovascular outcomes with SGLT2 inhibitors versus DPP4 inhibitors and GLP-1 receptor agonists in patients with heart failure with reduced and preserved ejection fraction

JGJimmy GonzalezRutgers, The State University of New Jersey BBBenjamin BatesRutgers, The State University of New Jersey SSSoko SetoguchiGeneral Cardiology

Key Result

SGLT2 inhibitors reduced the risk of hospitalization for heart failure by 33% compared to DPP4 inhibitors in patients with type 2 diabetes and HFrEF.

Study Design

Type

Cohort (n=47,379)

Structured PICO

Does initiation of SGLT2 inhibitors reduce hospitalization for heart failure and MI or stroke compared to DPP4 inhibitors or GLP-1 receptor agonists in older adults with type 2 diabetes and heart failure?

Population

47,379 US Medicare fee-for-service beneficiaries >65 years of age with type 2 diabetes and heart failure (HFrEF or HFpEF). Four cohorts: HFrEF SGLT2i vs DPP4i (n=13,882), HFrEF SGLT2i vs GLP-1RA (n=6,951), HFpEF SGLT2i vs DPP4i (n=17,493), HFpEF SGLT2i vs GLP-1RA (n=9,053). Excluded: gestational or type 1 diabetes, cancer, end-stage renal disease, HIV.

Intervention

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a class

Comparator

Dipeptidyl peptidase 4 inhibitors (DPP4i) or glucagon-like peptide-1 receptor agonists (GLP-1RA) as a class, adjusted using inverse probability of treatment weighting (IPTW)

Outcome

(1) Hospitalization for heart failure (HHF) and (2) myocardial infarction (MI) or stroke hospitalizationshard clinical

In older adults with type 2 diabetes and heart failure, initiation of SGLT2 inhibitors is associated with a significantly lower risk of heart failure hospitalization compared to DPP4 inhibitors and GLP-1 receptor agonists, regardless of ejection fraction.

Main Result

Effect estimate: HR 0.67 (95% CI 0.63, 0.72)

Absolute Event Rate: 52.2% vs 80.9%

Limitations

Susceptible to residual confounding due to observational nature
Lack of direct clinical variables like HbA1c, body weight, or HF severity in claims data
Generalizable mainly to older adults in Medicare fee-for-service
Lacked power for individual SGLT2i comparisons
Unable to study heart failure patients without diabetes

Abstract

BACKGROUND: No study has compared the cardiovascular outcomes for sodium-glucose cotransporter-2 inhibitors (SGLT2i) head-to-head against other glucose-lowering therapies, including dipeptidyl peptidase 4 inhibitor (DDP4i) or glucagon-like peptide-1 receptor agonist (GLP-1RA)-which also have cardiovascular benefits-in patients with heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction. METHODS: Medicare fee-for-service data (2013-2019) were used to create four pair-wise comparison cohorts of type 2 diabetes patients with: (1a) HFrEF initiating SGLT2i versus DPP4i; (1b) HFrEF initiating SGLT2i versus GLP-1RA; (2a) HFpEF initiating SGLT2i versus DPP4i; and (2b) HFpEF initiating SGLT2i versus GLP-1RA. The primary outcomes were (1) hospitalization for heart failure (HHF) and (2) myocardial infarction (MI) or stroke hospitalizations. Adjusted hazards ratios (HR) and 95% CIs were estimated using inverse probability of treatment weighting. RESULTS: Among HFrEF patients, initiation of SGLT2i versus DPP4i (cohort 1a; n = 13,882) was associated with a lower risk of HHF (adjusted Hazard Ratio HR (95% confidence interval), 0.67 (0.63, 0.72) and MI or stroke (HR: 0.86 0.75, 0.99), and initiation of SGLT2i versus GLP-1RA (cohort 1b; n = 6951) was associated with lower risk of HHF (HR: 0.86 0.79, 0.93), but not MI or stroke (HR: 1.02 0.85, 1.22). Among HFpEF patients, initiation of SGLT2i versus DPP4i (cohort 2a; n = 17,493) was associated with lower risk of HHF (HR: 0.65 0.61, 0.69) but not MI or stroke (HR: 0.90 0.79, 1.02), and initiation of SGLT2i versus GLP-1RA (cohort 2b; n = 9053) was associated with lower risk of HHF (0.89 0.83, 0.96), but not MI or stroke (HR: 0.97 0.83, 1.14). Results were robust across range of secondary outcomes (e.g., all-cause mortality) and sensitivity analyses. CONCLUSIONS: Bias from residual confounding cannot be ruled out. Use of SGLT2i was associated with reduced risk of HHF against DPP4i and GLP-1RA, reduced risk of MI or stroke against DPP4i within the HFrEF subgroup, and comparable risk of MI or stroke against GLP-1RA. Notably, the magnitude of cardiovascular benefit conferred by SGLT2i was similar among patients with HFrEF and HFpEF.

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