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Dapagliflozin Added to Usual Care in Individuals with Type 2 Diabetes Mellitus with Preexisting Cardiovascular Disease: A 24‐Week, Multicenter, Randomized, Double‐Blind, Placebo‐Controlled Study with a 28‐Week Extension
Author(s) -
Leiter Lawrence A.,
Cefalu William T.,
Bruin Tjerk W. A.,
GauseNilsson Ingrid,
Sugg Jennifer,
Parikh Shamik J.
Publication year - 2014
Publication title -
journal of the american geriatrics society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.992
H-Index - 232
eISSN - 1532-5415
pISSN - 0002-8614
DOI - 10.1111/jgs.12881
Subject(s) - dapagliflozin , medicine , placebo , diabetes mellitus , clinical endpoint , body mass index , blood pressure , randomization , type 2 diabetes , randomized controlled trial , weight loss , endocrinology , obesity , alternative medicine , pathology
Objectives To assess the efficacy of dapagliflozin, a sodium–glucose cotransporter 2 inhibitor, for the treatment of individuals with type 2 diabetes mellitus (T2 DM ) and preexisting cardiovascular disease ( CVD ). Design Randomized, double‐blind, age‐stratified (<65 and ≥65), 24‐week clinical trial with a 28‐week extension. Setting One hundred seventy‐three centers in 10 countries. Participants Individuals (N = 964) with T2 DM , glycosylated hemoglobin (HbA1c) of 7.0% to 10.0%, and documented CVD . Intervention Dapagliflozin 10 mg/d or placebo was added to usual care. Participants receiving insulin had their total daily insulin dose reduced by 25% at randomization. Measurements Two equal primary end points: change from baseline in HbA1c and proportion of participants achieving a three‐item end point (reduction of ≥0.5% in HbA1c, ≥3% in body weight, and ≥3 mmHg in systolic blood pressure) at 24 weeks. Results Forty‐seven percent were aged 65 and older, 7.7% were aged 75 and older, mean duration of T2 DM was 13 years, mean baseline HbA1c was 8.1%, and approximately 60% were taking insulin. The placebo‐corrected change in HbA1c with dapagliflozin was −0.4% at 24 weeks. Significantly more participants achieved the three‐item end point with dapagliflozin (10.0%) than with placebo (1.9%). The placebo‐corrected percentage change in body weight for dapagliflozin was −1.9% (−1.8 kg). Similar results were observed in both age strata, and changes were maintained over 52 weeks. More than one‐quarter (28.2%) of participants receiving dapagliflozin and 25.3% of those receiving placebo experienced hypoglycemia. More participants receiving dapagliflozin had vulvovaginitis, balanitis, or urinary tract infection. Conclusion When added to a usual background regimen in an older population with advanced T2 DM and preexisting comorbid CVD , dapagliflozin improved glycemic control without an increase in hypoglycemic risk, promoted weight loss, and was well tolerated.