What’s noteworthy about the study, say the researchers, is that dapagliflozin leads to loss of fat mass, with significant reductions vs placebo in both abdominal visceral adipose tissue and subcutaneous adipose tissue.
Dapagliflozin, a highly selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), belongs to a new class of anti-diabetes drugs designed to allow more sugar to be excreted with urine.
In clinical trials, the drug’s been shown to improve glycemic control in patients with type 2 diabetes when used alone, or when added to metformin, glimepiride or insulin. Moderate weight loss has been a consistent finding in these trials, but the exact make up of that weight loss has been unknown.
The objective of the current study, say the investigators, was to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid.
Dr. Jan Bolinder from the Karolinska Institute in Stockholm and colleagues had 182 overweight middle-aged patients with type 2 diabetes inadequately controlled by metformin add dapagliflozin 10 mg daily or placebo for 24 weeks. As is common with diabetes trials, all patients received general diet and exercise advice.
In a report online February 1 in the Journal of Endocrinology and Metabolism, Dr. Bolinder and colleagues report that the addition of dapagliflozin improved glycemic control (as expected) and yielded a placebo-corrected reduction in total body weight of 2.1 kg at 24 weeks (p<0.0001).
Compared with placebo, dapagliflozin treatment showed statistically-significant reductions in waist circumference (-1.52 cm; p=0.0143) and fat mass (-1.48 kg; p=0.0001) and in the proportion of patients achieving weight loss of at least 5% (26.2%; p<0.0001). About two-thirds of the weight loss observed with dapagliflozin was attributable to reductions in fat mass as measured by dual-energy x-ray absorptiometry (fat mass vs lean mass, -2.2 vs -1.1 kg), they say.
The researchers say longer-term data are needed to establish whether the weight loss observed with dapagliflozin therapy is sustained. [disc1]
In terms of safety, the proportions of patients with at least one adverse event were similar in the dapagliflozin (43%) and the placebo arm (40%). More patients taking dapagliflozin experienced a serious adverse event (6.6% vs 1.1%), or were taken off study medication due to a serious adverse event (4.4% vs 0.0%). Two patients on dapagliflozin and three on placebo experienced at least one hypoglycemic event; none of these events were classified as major. As seen in prior studies, events suggestive of genital infections and lower urinary tract infections were seen more often in the dapagliflozin arm.
v (See Reuters Health story of Jan 19, 2012). Several of the authors on the current study have ties with pharmaceutical companies including AstraZeneca. A complete list can be found with the original article.
Effects of Dapagliflozin on Body Weight, Total Fat Mass, and Regional Adipose Tissue Distribution in Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Metformin
The Journal of Clinical Endocrinology & Metabolism 2012