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Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With SGLT2 Inhibitors vs Metformin
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
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.
Additional Info
Disclosure statements are available on the authors' profiles:
Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors Versus Metformin : A Cohort Study
Ann. Intern. Med 2022 May 24;[EPub Ahead of Print], H Shin, S Schneeweiss, RJ Glynn, E PatornoFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The cardioprotective effects of sodium–glucose cotransporter-2 inhibitors (SGLT-2i) are well-documented in several populations including type 2 diabetes (T2D), heart failure, and chronic kidney disease. However, data on the cardiovascular outcomes of first-line treatment with SGLT-2i are limited due to the small number of participants with T2D not on metformin in randomized trials. In this population-based cohort study, SGLT-2i use was associated with a similar rate of myocardial infarction (MI)/stroke/mortality and a lower rate of hospitalization for heart failure (HHF)/mortality (primarily driven by a 22% lower rate of HHF), suggesting a possible benefit of SGLT-2i as a first-line treatment. Differences in observed rates of safety events between the treatment groups were negligible for acute kidney injury, bone fractures, severe hypoglycemia, severe urinary tract infections, diabetic ketoacidosis, and lower limb amputations. A higher incidence of genital infections was found in the SGLT-2i group. Several sensitivity analyses supported the efficacy observations.
These results are qualitative like previous randomized trials and meta-analyses of SGLT-2i versus placebo, with greatest cardiovascular efficacy on HHF and consistently higher rates of genital infections. Despite careful propensity score matching, non-randomized comparisons of therapy have the risk of confounding, including confounding by indication, socioeconomic status, and other measured or unmeasured variables. The risk of confounding may be increased given the much smaller group of first-line SGLT-2i use (1.1% of the cohort). These results, therefore, should be considered as hypothesis-generating. However, these data are consistent with a broad range of subgroups of clinical trials showing consistent benefits of SGLT-2i in multiple populations. In heart failure and renal studies that included patients without diabetes, results have been largely consistent between diabetes and non-diabetes patients, suggesting that effects are not dependent on diabetes or use of other diabetes therapies analogous to first-therapy. Current diabetes therapy guidelines include the use of SGLT-2i in appropriate patients as first-line therapy.1 Although randomized data would be preferred and are anticipated in the future, these data in context of a growing body of trial evidence supporting SGLT-2i provide compelling support for this recommendation.
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