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Cardiovascular Outcomes Comparing First-Line SGLT-2i vs. Metformin
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- Patients initiating treatment with first-line SGLT-2i had a similar risk for MI/stroke/mortality but lower risk for hospitalization for heart failure (HHF)/mortality and HHF compared with those initiating treatment with metformin.
- These findings would support the use of SGLT-2i as first-line T2D treatment for cardiovascular outcomes.
- Given limitations of the current study design, there is a need for additional prospective randomized studies to provide more definitive evidence.
Study Questions:
What are the cardiovascular outcomes among adults with type 2 diabetes (T2D) who initiated first-line treatment with sodium–glucose cotransporter-2 inhibitors (SGLT-2i) versus metformin?
Methods:
The investigators conducted a population-based cohort study using claims data from two large US commercial and Medicare databases (April 2013–March 2020). Patients with T2D aged ≥18 years (>65 years in Medicare) initiating treatment with SGLT-2i or metformin during April 2013–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% confidence intervals (CIs) were reported for first-line SGLT-2i (canagliflozin, empagliflozin, or dapagliflozin) or metformin. 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. The authors calculated database-specific unadjusted and propensity score-matched numbers of events, incidence rates, and incidence rate differences per 1,000 person-years with 95% CIs for all outcomes.
Results:
Among 8,613 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, 0.77-1.19) and a lower risk for HHF/mortality (HR, 0.80; CI, 0.66-0.97) during a mean follow-up of 12 months. Initiators receiving SGLT-2i showed a lower risk for HHF (HR, 0.78; CI, 0.63-0.97), a numerically lower risk for MI (HR, 0.70; CI, 0.48-1.00), 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, 1.91-2.51) and otherwise similar safety as those receiving metformin.
Conclusions:
The authors concluded that 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.
Perspective:
This population-based cohort study reports that patients initiating treatment with first-line SGLT-2i had a similar risk for MI/stroke/mortality and lower risk for HHF/mortality and HHF compared with those initiating treatment with metformin. Of note, the risk for adverse events was similar except for an increased risk for genital infections among SGLT-2i initiators. These findings support the use of SGLT-2i as first-line T2D treatment for cardiovascular outcomes, but given limitations of the current study design, there is a need for additional prospective randomized studies to provide more definitive evidence.
Clinical Topics: Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, Acute Heart Failure
Keywords: Cardiometabolic Risk Factors, Diabetes Mellitus, Type 2, Genitalia, Heart Failure, Hemorrhagic Stroke, Metformin, Myocardial Infarction, Myocardial Ischemia, Outcome Assessment, Health Care, Primary Prevention, Sodium-Glucose Transporter 2 Inhibitors
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