Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding.Objectives:
Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components.Design and Setting:
This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries.Patients:
Included were 182 patients with T2DM (mean values: women 63.3 and men 58.6 yr of age; hemoglobin A1c 7.17%, body mass index 31.9 kg/m2, and body weight 91.5 kg) inadequately controlled on metformin.Intervention:
Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk.Main Outcome Measures:
Primary endpoint was total body weight (TBW) change from baseline at wk 24. Key secondary endpoints were waist circumference and dual-energy x-ray absorptiometry total-body fat mass (FM) changes from baseline at wk 24, and patient proportion achieving body weight reduction of at least 5% at wk 24. In a subset of patients, magnetic resonance assessment of visceral adipose tissue (VAT) and sc adipose tissue (SAT) volume and hepatic lipid content were also evaluated.Results:
At wk 24, placebo-corrected changes with dapagliflozin were as follows: TBW, −2.08 kg [95% confidence interval (CI) = −2.84 to −1.31; P < 0.0001]; waist circumference, −1.52 cm (95% CI = −2.74 to −0.31; P = 0.0143); FM, −1.48 kg (95% CI = −2.22 to −0.74; P = 0.0001); proportion of patients achieving weight reduction of at least 5%, +26.2% (95% CI = 15.5 to 36.7; P < 0.0001); VAT, −258.4 cm3 (95% CI = −448.1 to −68.6; nominal P = 0.0084); SAT, −184.9 cm3 (95% CI = −359.7 to −10.1; nominal P = 0.0385). In the dapagliflozin vs. placebo groups, respectively, serious adverse events were reported in 6.6 vs. 1.1%; events suggestive of vulvovaginitis, balanitis, and related genital infection in 3.3 vs. 0%; and lower urinary tract infections in 6.6 vs. 2.2%.Conclusions:
Dapagliflozin reduces TBW, predominantly by reducing FM, VAT and SAT in T2DM inadequately controlled with metformin.