Study investigating metformin versus an sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitor) as first-line treatment in type 2 diabetes

Metformin versus an Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2 inhibitor) as first-line treatment in type 2 diabetes

• a population based cohort study was undertaken to assess cardiovascular outcomes among adults with type 2 diabetes (T2D) who initiated first-line treatment with SGLT2 inhibitors (SGLT-2i) versus 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.
  • study results: among 8613 first-line SGLT-2i initiators matched to 17226 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
  • the study 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
  • limitations of study
    • treatment selection was not randomized - therefore there could be an unstated bias for why a patient was started on an SGLT2i rather than metformin e.g. thought to be more at risk of heart failure which could then explain the greater heart failure related benefits in this cohort
    • the study was only for 12 months - most of the CVOT (cardiovascular outcome trials) related to the use of diabetes medications (and the sources of the CV benefit signals seen in trials such as EMPA-REG) are generally 3 years or more

Reference:

• Shin H, Schneeweiss S, Glynn RJ, Patorno E. 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. doi: 10.7326/M21-4012. Epub ahead of print. PMID: 35605236
• Zinman B, Wanner C, Lachin JM et al., Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; DOI: 10.1056/NEJMoa1504720