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Sodium‐glucose co‐transporter‐2 inhibitors versus dipeptidyl peptidase‐4 inhibitors and the risk of heart failure: a nationwide cohort study of older adults with diabetes mellitus


Aims — SGLT2 inhibitors decrease the risk of heart failure among middle‐aged adults. Whether this benefit also applies to older adults is unknown. The aim of this study is to analyze the rate of heart failure hospitalization for older adults prescribed an SGLT2‐inhibitor.

Materials and Methods — Cohort study of adults over 65 years diagnosed with diabetes mellitus in Ontario, Canada, from July 2015 to March 2019 who received either an SGLT2 inhibitor or DPP4‐inhibitor. The primary outcome was a composite of heart failure hospitalization and all‐cause mortality. Secondary outcomes included diabetic ketoacidosis and hypoglycemia.

Results — 29,916 adults prescribed an SGLT2‐inhibitor were compared to 29,916 adults prescribed a DPP4‐inhibitor. The mean age was 72, 60% were men, the baseline hemoglobin A1C was 8.2% and the baseline creatinine was 89 mmol/L. The incidence rate of the primary outcome was 19/1,000 person‐years for adults prescribed an SGLT2 inhibitor compared to 38/1,000 person‐years in those prescribed a DPP4 inhibitor. This results in a hazard ratio (HR) of 0.49, (95% confidence interval (CI):0.45‐0.54) and a rate difference (RD) of 19 less events per 1,000 person‐years (RD=‐19,95% CI ‐22,‐17). Patients prescribed an SGLT2‐inhibitor also had a lower rate of hypoglycemia (HR=0.61,95% CI 0.46‐0.81); RD=‐1.6 (95% CI ‐2.4,‐0.8) but a higher rate of diabetic ketoacidosis (HR=1.84,95% CI 1.26‐2.70); RD=1.0 (95% CI 0.4‐1.6).

Conclusions — Older adults prescribed an SGLT2‐inhibitor had a lower rate of heart failure hospitalization or death, and a lower rate of hypoglycemia, but an increased rate of diabetic ketoacidosis compared to older adults prescribed a DPP4‐inhibitor.



Fralick M, Colacci M, Thiruchelvam D, Gomes T, Redelmeier DA. Diabetes Obes Metab. 2021; 23(4):950-60. Epub 2020 Dec 18.

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