Weight Loss Drug Therapy in Type 2 Diabetes

The long-acting glucagon-like peptide-1 receptor agonist liraglutide appears to promote long-term weight loss among patients with type 2 diabetes mellitus (T2DM), according to the results of a large international trial.

Weight loss of 5-10% can improve T2DM and related comorbidities, but few safe, effective weight-management drugs are currently available, note the authors, led by Melanie J. Davies, MD, of the Diabetes Research Centre, University of Leicester, Leicester, United Kingdom.

Liraglutide may be a useful pharmacotherapy for diabetes patients looking to lose weight when used in combination with intensive lifestyle interventions. The drug’s manufacturer, Novo Nordisk, began marketing it in the U.S. under the brand name Saxenda early this year as a treatment for obesity in adults with at least 1 weight-related comorbid condition. It was approved by the FDA on December 23, 2014 for treatment for obesity in adults with some related comorbidity.

In the trial, 846 overweight or obese patients with T2DM randomized to once-daily liraglutide 1.8 mg (the upper dose approved for treating T2DM, sold as Victoza), 3-mg liraglutide (Saxenda), or placebo, along with a low-calorie diet (500 kcal per day) and exercise (150 minutes or more per week).

The adult patients had a body mass index (BMI) of 27 kg/m² or greater, were taking 0 to 3 oral hypoglycemic agents (metformin, thiazolidinedione, or sulfonylurea) with stable body weight, and had glycated hemoglobin levels of 7-10%.

At 56 weeks, the patients’ body weight loss averaged 6% for the 3-mg dose, 4.7% for the 1.8-mg dose, and 2% with placebo. Weight loss greater than 10% occurred in 25.2% with liraglutide 3 mg and 15.9% with liraglutide 1.8 mg compared to 6.7% with placebo. The proportions of patients losing at least 5% of their initial body weight were 54%, 40%, and 21%, respectively.

Significant reductions in mean waist circumference and BMI were also seen with both liraglutide doses compared with placebo.

More than two-thirds of patients achieved HbA_1c levels of less than 7% with liraglutide compared to only 27% with placebo.

More gastrointestinal disorders were reported with the higher dose liraglutide group than those who took the lower dose of the drug or placebo. The most commonly reported adverse events were nausea, vomiting, and diarrhea. These typically occurred early in treatment and were mild in severity. No pancreatitis was reported.

Serious adverse events occurred in 9% of both liraglutide groups and in 6% of the placebo group. There was one death, of a pulmonary embolism, in the 1.8-mg group.

In conclusion, the authors state: “Among overweight and obese participants with type 2 diabetes, use of subcutaneous liraglutide (3.0 mg) daily, compared with placebo, resulted in weight loss over 56 weeks. Further studies are needed to evaluate longer-term efficacy and safety.”

In an exploratory analysis comparing the 2 doses, the higher dose was statistically significantly better with regard to weight-loss measures and glycemic control than the lower dose. Currently, no study has examined whether switching diabetes patients from the 1.8-mg to the 3-mg dose would improve weight loss.