Efficacy and Safety of Dapagliflozin in the Elderly: Analysis From the DECLARE-TIMI 58 Study

Cahn, Avivit, Mosenzon, Ofri, Wiviott, Stephen D, Rozenberg, Aliza, Yanuv, Ilan, Goodrich, Erica L, Murphy, Sabina A, Bhatt, Deepak L, Leiter, Lawrence A, McGuire, Darren K
et al (show 7 more authors) (2020) Efficacy and Safety of Dapagliflozin in the Elderly: Analysis From the DECLARE-TIMI 58 Study. DIABETES CARE, 43 (2). pp. 468-475.

[img] Text
elderly in declare DC submission revision CLEAN.docx - Author Accepted Manuscript

Download (391kB)


<h4>Objective</h4>Data regarding the effects of sodium-glucose cotransporter 2 inhibitors in the elderly (age ≥65 years) and very elderly (age ≥75 years) are limited.<h4>Research design and methods</h4>The Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 assessed cardiac and renal outcomes of dapagliflozin versus placebo in patients with type 2 diabetes. Efficacy and safety outcomes were studied within age subgroups for treatment effect and age-based treatment interaction.<h4>Results</h4>Of the 17,160 patients, 9,253 were <65 years of age, 6,811 ≥65 to <75 years, and 1,096 ≥75 years. Dapagliflozin reduced the composite of cardiovascular death or hospitalization for heart failure consistently, with a hazard ratio (HR) of 0.88 (95% CI 0.72, 1.07), 0.77 (0.63, 0.94), and 0.94 (0.65, 1.36) in age-groups <65, ≥65 to <75, and ≥75 years, respectively (interaction <i>P</i> value 0.5277). Overall, dapagliflozin did not significantly decrease the rates of major adverse cardiovascular events, with HR 0.93 (95% CI 0.81, 1.08), 0.97 (0.83, 1.13), and 0.84 (0.61, 1.15) in age-groups <65, ≥65 to <75, and ≥75 years, respectively (interaction <i>P</i> value 0.7352). The relative risk reduction for the secondary prespecified cardiorenal composite outcome ranged from 18% to 28% in the different age-groups with no heterogeneity. Major hypoglycemia was less frequent with dapagliflozin versus placebo, with HR 0.97 (95% CI 0.58, 1.64), 0.50 (0.29, 0.84), and 0.68 (0.29, 1.57) in age-groups <65, ≥65 to <75, and ≥75 years, respectively (interaction <i>P</i> value 0.2107). Safety outcomes, including fractures, volume depletion, cancer, urinary tract infections, and amputations were balanced with dapagliflozin versus placebo, and acute kidney injury was reduced, all regardless of age. Genital infections that were serious or led to discontinuation of the study drug and diabetic ketoacidosis were uncommon, yet more frequent with dapagliflozin versus placebo, without heterogeneity (interaction <i>P</i> values 0.1058 and 0.8433, respectively).<h4>Conclusions</h4>The overall efficacy and safety of dapagliflozin are consistent regardless of age.

Item Type: Article
Uncontrolled Keywords: Kidney, Cardiovascular System, Humans, Urinary Tract Infections, Diabetic Ketoacidosis, Diabetes Mellitus, Type 2, Hypoglycemia, Benzhydryl Compounds, Glucosides, Hypoglycemic Agents, Treatment Outcome, Incidence, Survival Analysis, Age Factors, Aging, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Sodium-Glucose Transporter 2 Inhibitors
Depositing User: Symplectic Admin
Date Deposited: 20 Dec 2019 09:36
Last Modified: 19 Jan 2023 00:12
DOI: 10.2337/dc19-1476
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3067208