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Dapagliflozin reduces weight through glucose excretion, not fluid loss
8 February 2012
MedWire News: Adding dapagliflozin to metformin results in significant weight loss among diabetes patients principally as a result of caloric loss through glucose excretion rather than fluid loss, report researchers.
The findings come from a study investigating the underlying components of the weight-reducing effects of dapagliflozin that have consistently been observed in previous studies.
Led by Jan Bolinder (Karolinska Institutet, Stockholm, Sweden), the team recruited 182 patients, with a mean glycated hemoglobin (HbA1c) level of 7.17%, a body mass index of 31.9 kg/m2, and a body weight of 91.5 kg, who had been inadequately controlled on a stable dose of metformin (1500 mg/day) for at least 12 weeks.
The researchers aimed to determine the relative contribution of changes from baseline in fat mass (FM) versus lean mass (LM [incorporating the fluid component]) to overall weight loss using whole-body dual-energy X-ray absorptiometry (DXA).
The team randomly allocated the patients to receive either dapagliflozin 10 mg or placebo once daily as an add-on therapy to continuing open-label metformin monotherapy for a period of 24 weeks, and compared their baseline measurements of body weight, body composition, and glycemic variables with those taken at the end of the study.
As reported in the Journal of Clinical Endocrinology and Metabolism, patients receiving dapagliflozin had significantly greater reductions in mean total body weight, HbA1c, and fasting plasma glucose than did those receiving placebo over the study period, by 2.96 kg, 0.28%, and 17.1 mg/dL, respectively.
Treatment with dapagliflozin also resulted in significantly greater reductions in mean waist circumference, FM, LM, visceral adipose tissue, and subcutaneous adipose tissue, (1.52 cm, 1.48 kg, 0.6 kg, 258.4cm3, and 184.9 cm3, respectively) and a significantly greater increase in the proportion of patients achieving weight reduction of at least 5% (26.2%).
The authors also report that about two-thirds of the weight loss observed with dapagliflozin was attributable to reductions in fat (FM vs LM, 2.20 vs 1.10 kg), and for weight loss with placebo, about one half was attributable to reductions in fat (FM vs LM, 0.74 vs 0.60 kg).
“Moreover, the reductions in total body weight, fat mass, and waist circumference with dapagliflozin treatment occurred in the context of a sustained elevation in spot urinary glucose excretion, which itself was significantly associated with decreases in total body weight and fat mass,” write the researchers, who add that this supports that caloric loss from glucosuria, and not fluid loss, was principally responsible for these changes.
“Dapagliflozin reduces hyperglycemia in patients with Type 2 diabetes by increasing urinary glucose excretion, and weight loss is a consistent associated finding,” write Bolinder and team.
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