Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors Versus Metformin

May 23, 2022Annals of internal medicine

Heart health outcomes in people starting type 2 diabetes treatment with SGLT2 inhibitors versus metformin

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Abstract

Among 8,613 adults with type 2 diabetes initiating treatment, SGLT-2 inhibitors are associated with a lower risk for hospitalization due to heart failure compared to metformin.

SGLT-2 inhibitor initiators had a hazard ratio of 0.80 for hospitalization for heart failure or all-cause mortality compared to metformin initiators.
The risk for myocardial infarction, ischemic or hemorrhagic stroke, and all-cause mortality was similar between SGLT-2 inhibitor and metformin users (HR, 0.96).
SGLT-2 inhibitor users showed a lower risk for hospitalization due to heart failure (HR, 0.78) and a numerically lower risk for myocardial infarction (HR, 0.70).
No difference was observed in risk for stroke, mortality, and the composite of myocardial infarction, stroke, heart failure hospitalization, or mortality between the two groups.
SGLT-2 inhibitor initiators had a higher risk for genital infections (HR, 2.19) while having a similar overall safety profile compared to metformin initiators.

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BACKGROUND: Evidence on the risk for cardiovascular events associated with use of first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared with metformin is limited.

OBJECTIVE: To assess cardiovascular outcomes among adults with type 2 diabetes (T2D) who initiated first-line treatment with SGLT-2i versus metformin.

DESIGN: Population-based cohort study.

SETTING: Claims data from 2 large U.S. commercial and Medicare databases (April 2013 to March 2020).

PARTICIPANTS: Patients with T2D aged 18 years and older (>65 years in Medicare) initiating treatment with SGLT-2i or metformin during April 2013 to March 2020, without any use of antidiabetic medications before cohort entry, were identified. After 1:2 propensity score matching in each database, pooled hazard ratios (HRs) and 95% CIs were reported.

INTERVENTION: First-line SGLT-2i (canagliflozin, empagliflozin, or dapagliflozin) or metformin.

MEASUREMENTS: Primary outcomes were a composite of hospitalization for myocardial infarction (MI), hospitalization for ischemic or hemorrhagic stroke or all-cause mortality (MI/stroke/mortality), and a composite of hospitalization for heart failure (HHF) or all-cause mortality (HHF/mortality). Safety outcomes including genital infections were assessed.

RESULTS: Among 8613 first-line SGLT-2i initiators matched to 17 226 metformin initiators, SGLT-2i initiators had a similar risk for MI/stroke/mortality (HR, 0.96; 95% CI, 0.77 to 1.19) and a lower risk for HHF/mortality (HR, 0.80; CI, 0.66 to 0.97) during a mean follow-up of 12 months. Initiators receiving SGLT-2i showed a lower risk for HHF (HR, 0.78; CI, 0.63 to 0.97), a numerically lower risk for MI (HR, 0.70; CI, 0.48 to 1.00), and similar risk for stroke, mortality, and MI/stroke/HHF/mortality compared with metformin. Initiators receiving SGLT-2i had a higher risk for genital infections (HR, 2.19; CI, 1.91 to 2.51) and otherwise similar safety as those receiving metformin.

LIMITATION: Treatment selection was not randomized.

CONCLUSION: As first-line T2D treatment, initiators receiving SGLT-2i showed a similar risk for MI/stroke/mortality, lower risk for HHF/mortality and HHF, and a similar safety profile except for an increased risk for genital infections compared with those receiving metformin.

PRIMARY FUNDING SOURCE: Brigham and Women's Hospital and Harvard Medical School.

Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors Versus Metformin

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