Phase 3 clinical trial evaluating the effects of dapaglifozin on weight loss in overweight patients with type 2 diabetes mellitus

This research evaluated the effect of dapagliflozin on weight loss in patients with type 2 diabetes mellitus (T2DM) uncontrolled with metformin therapy. The results showed that dapagliflozin reduced blood sugar levels by reducing patients’ weight and increasing the elimination of glucose in urine.

T2DM is a condition in which patients have high blood sugar levels (hyperglycemia), mainly due to insulin resistance (the body cannot properly use glucose as energy). Another mechanism for hyperglycemia is when the pancreas does not produce enough insulin. Treatment options available for patients with T2DM include oral anti-diabetic drugs (OAD) and insulin injections. However, many of these treatments have been associated with some side effects such as weight gain, hypoglycemia (abnormally low blood sugar) or fluid retention. Dapagliflozin (Forxiga) is a OAD used to treat patients with T2DM, alone or in combination with other OAD. Dapaglifozin works by eliminating glucose through the urine (glycosuria). Glycosuria reduces body fat and increases the loss of fluids, leading to rapid weight loss. However, the increased amount of glucose in the urine leads to tiredness, dehydration and an increased risk of urinary tract infections. 

This phase 3 clinical trial included 182 patients with T2DM who were overweight and whose disease was not well controlled with metformin therapy. In addition to metformin, the patients were randomly assigned to receive either dapaglifozin or placebo (a substance with no effect on the body, used as a control in testing new drugs). All patients also received advice on lifestyle, diet and physical exercise. The main parameters evaluated were changes in body weight, in the waistline (a larger waistline is associated with diabetes complications) and total body fat measured with a test called dual-energy x-ray absorptiometry (DXA). Safety was also evaluated through reported side effects.

After 24 weeks of treatment, patients who received dapaglifozin had lost 2.5 to 3.5 kg compared to patients in the placebo group who had lost 0.4 to 1.5 kg. Compared to patients who received placebo, patients treated with dapaglifozin had a significant reduction in waistline (0.3 cm compared to 1.5 cm) and in total body fat (0.75 kg versus 1.5 kg). However, more patients in the dapaglifozin group reported adverse effects (42.9%) compared to patients who received placebo (39.6%). The most common side effects reported by these patients were common cold, high blood pressure, bladder infection or pneumonia.  

In summary, this study showed that the use of dapagliflozin was associated with weight loss and improved blood sugar control in overweight patients with T2DM uncontrolled with metformin.  

A limitation of this study stems from the fact that it included a small group of patients who were followed up for a short period of time. As of January 2014, dapagliflozin is approved by the FDA  for the management of type 2 diabetes.

This study was funded by AstraZeneca and Bristol-Myers Squibb, the manufacturers of Forxiga.