Primary Occurrence of Cardiovascular Events After Adding Sodium–Glucose Cotransporter-2 Inhibitors or Glucagon-like Peptide-1 Receptor Agonists Compared With Dipeptidyl Peptidase-4 Inhibitors: A Cohort Study in Veterans With Diabetes

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Diabetes. Intervention: GLP1RA or SGLT2i vs. DPP4i. Primary outcome: MACE (acute myocardial infarction, stroke, or cardiovascular death) and heart failure (HF) hospitalization (aHR 0.82, 95% CI 0.72 to 0.94).

Tadarro L. Richardson; Alese E. Halvorson; Amber J. Hackstadt; Adriana M. Hung; Robert A. Greevy; Carlos G. Grijalva; Tom A. Elasy; Christianne L. Roumie

doi:10.7326/m22-2751

May 8, 2023Annals of Internal MedicineOpen Access

Primary Occurrence of Cardiovascular Events After Adding Sodium–Glucose Cotransporter-2 Inhibitors or Glucagon-like Peptide-1 Receptor Agonists Compared With Dipeptidyl Peptidase-4 Inhibitors: A Cohort Study in Veterans With Diabetes

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Key result

Adding GLP1RA linked to ~18% lower MACE and HF hospitalization versus DPP4i, unlike SGLT2i.

aHR 0.82
95% CI 0.72 to 0.94

Why the study?

The effectiveness of GLP1RA and SGLT2i in preventing MACE was uncertain for patients without preexisting cardiovascular disease.

Does the addition of GLP1RA or SGLT2i reduce MACE and HF hospitalization compared with DPP4i in veterans with diabetes without preexisting cardiovascular disease?

Study Design

Type

Cohort

Multicenter

Yes

Structured PICO

Does the addition of GLP1RA or SGLT2i reduce MACE and HF hospitalization compared with DPP4i in veterans with diabetes without preexisting cardiovascular disease?

P

Population

U.S. veterans aged 18 years or older with diabetes and without preexisting cardiovascular disease (primary prevention), adding GLP1RA, SGLT2i, or DPP4i onto metformin, sulfonylurea, or insulin treatment. Median age 67 years, diabetes duration 8.5 years. Total N=99,757.

I

Intervention

Addition of a glucagon-like peptide-1 receptor agonist (GLP1RA) or sodium-glucose cotransporter-2 inhibitor (SGLT2i) onto metformin, sulfonylurea, or insulin treatment alone or in combination.

C

Comparator

Addition of a dipeptidyl peptidase-4 inhibitor (DPP4i) onto metformin, sulfonylurea, or insulin treatment alone or in combination.

O

Outcome

Composite of MACE (acute myocardial infarction, stroke, or cardiovascular death) and heart failure (HF) hospitalization.composite

Main Result

Effect estimate: aHR 0.82 (95% CI 0.72 to 0.94)

In veterans with diabetes without prior cardiovascular disease, adding a GLP1RA, but not an SGLT2i, to standard therapy was associated with a reduced risk of MACE and heart failure hospitalization compared to adding a DPP4i.

Limitations

Residual confounding
Use of DPP4i, GLP1RA, and SGLT2i as first-line therapies were not examined
use of DPP4i, GLP1RA, and SGLT2i as first-line therapies were not examined

Implication

Should not yet change practice in veterans with diabetes without CVD; leaves open comparative effectiveness of GLP-1RA versus SGLT2i additions.

Abstract

BACKGROUND: The effectiveness of glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in preventing major adverse cardiac events (MACE) is uncertain for those without preexisting cardiovascular disease. OBJECTIVE: To test the hypothesis that MACE incidence was lower with the addition of GLP1RA or SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) for primary cardiovascular prevention. DESIGN: Retrospective cohort study of U.S. veterans from 2001 to 2019. SETTING: Veterans aged 18 years or older receiving care from the Veterans Health Administration, with data linkage to Medicare, Medicaid, and the National Death Index. PATIENTS: Veterans adding GLP1RA, SGLT2i, or DPP4i onto metformin, sulfonylurea, or insulin treatment alone or in combination. Episodes were stratified by history of cardiovascular disease. MEASUREMENTS: Study outcomes were MACE (acute myocardial infarction, stroke, or cardiovascular death) and heart failure (HF) hospitalization. Cox models compared the outcome between medication groups using pairwise comparisons in a weighted cohort adjusted for covariates. RESULTS: The cohort included 28 759 GLP1RA versus 28 628 DPP4i weighted pairs and 21 200 SGLT2i versus 21 170 DPP4i weighted pairs. Median age was 67 years, and diabetes duration was 8.5 years. Glucagon-like peptide-1 receptor agonists were associated with lower MACE and HF versus DPP4i (adjusted hazard ratio [aHR], 0.82 [95% CI, 0.72 to 0.94]), yielding an adjusted risk difference (aRD) of 3.2 events (CI, 1.1 to 5.0) per 1000 person-years. Sodium-glucose cotransporter-2 inhibitors were not associated with MACE and HF (aHR, 0.91 [CI, 0.78 to 1.08]; aRD, 1.28 [-1.12 to 3.32]) compared with DPP4i. LIMITATION: Residual confounding; use of DPP4i, GLP1RA, and SGLT2i as first-line therapies were not examined. CONCLUSION: The addition of GLP1RA was associated with primary reductions of MACE and HF hospitalization compared with DPP4i use; SGLT2i addition was not associated with primary MACE prevention. PRIMARY FUNDING SOURCE: VA Clinical Science Research and Development and supported in part by the Centers for Diabetes Translation Research.

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Cite This Study

Richardson et al. (2023) conducted a cohort in Diabetes. GLP1RA or SGLT2i vs. DPP4i was evaluated on MACE (acute myocardial infarction, stroke, or cardiovascular death) and heart failure (HF) hospitalization (aHR 0.82, 95% CI 0.72 to 0.94). Adding GLP1RA to baseline diabetes therapy was associated with lower MACE and heart failure hospitalization compared with DPP4i (aHR 0.82; 95% CI 0.72-0.94), whereas SGLT2i addition was not.

synapsesocial.com/papers/6a0de09a1e1a6dfdb4bae551 https://doi.org/10.7326/m22-2751