March 10, 2023Cardiovascular DiabetologyOpen 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

Q: 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).

View Full Paper

Ask AI

Bookmark

Key result

SGLT2i linked to ~33% lower heart failure hospitalization risk versus DPP4i in HFrEF.

HR 0.67
95% CI 0.63, 0.72
n=47,379

Why the study?

No study has compared cardiovascular outcomes for SGLT2 inhibitors head-to-head against DPP4 inhibitors or GLP-1 receptor agonists in patients with HFrEF or HFpEF.

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?

Study Design

Type

Cohort (n=47,379)

Structured PICO

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

Main Result

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

Absolute Event Rate: 52.2% vs 80.9%

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.

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
Bias from residual confounding cannot be ruled out
Definitions to identify HF subtypes prioritize positive predictive values at the possible cost of lowered sensitivity (under-detection of patients with HF)

Implication

Supports SGLT2i preference over DPP4i for HHF reduction in T2D-HFrEF; leaves open effects versus GLP-1RA pending RCTs.

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.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Gonzalez et al. (2023) conducted a cohort in Type 2 diabetes with heart failure (HFrEF and HFpEF) (n=47,379). SGLT2 inhibitors vs. DPP4 inhibitors and GLP-1 receptor agonists was evaluated on Hospitalization for heart failure (HFrEF cohort, SGLT2i vs DPP4i) (HR 0.67, 95% CI 0.63, 0.72). SGLT2 inhibitors reduced the risk of hospitalization for heart failure by 33% compared to DPP4 inhibitors in patients with type 2 diabetes and HFrEF.

synapsesocial.com/papers/6a0de09a1e1a6dfdb4bae553 https://doi.org/10.1186/s12933-023-01784-w