June 15, 2009 (New Orleans, Louisiana) — An investigational compound that combines phentermine and a controlled-release formulation of topiramate (Qnexa [formerly VI-0521], Vivus) appears to stop progression toward type 2 diabetes in nondiabetic obese subjects.
Results of a clinical trial presented here at the American Diabetes Association (ADA) 69th Scientific Sessions show that the drug (one component of which is approved for the treatment of obesity and the other for pediatric epilepsy) changes the trajectory of hemoglobin A1c and appears to have the potential to halt progression to type 2 diabetes in obese nondiabetic subjects.
Results were presented by lead investigator Louis Aronne, MD, from the Department of Medicine at Weill-Cornell Medical Center and New York Presbyterian Hospital in New York City.
The 6-month phase 3 study involved 756 subjects aged 18 to 71 years (mean, 45.6), with a body mass index ranging from 30 to 45 kg/m2 (mean, 36.3) and a mean baseline A1c of 5.5%, were randomized to phentermine 7.5 or 15 mg, topiramate 46 or 92 mg, combinations of the 2 drugs (VI-0521) at either the lower 2 or the higher 2 doses, or placebo.
Treatment effect on A1c, metabolic parameters, and body weight were assessed.
Subjects were also placed on a 500 kcal deficit diet and received a structured lifestyle modification and exercise program.
Subjects in the placebo group lost 1.71% of their body weight. However, A1c increased by 0.09% during the course of the 6-month study (P < .0001, compared with baseline).
For VI-0521, subjects in the lower-dose combination group lost an average of 8.46% of their body weight, and those in the higher-dose combination group lost an average of 9.21%. A1c levels decreased 0.01% with the lower-dose combination and 0.02% with the higher-dose combination (P < .0001 for each dose, compared with placebo).
The most commonly observed adverse events, all mild and transient, were headache, paresthesia, upper respiratory infection, dry mouth, nasopharyngitis, and constipation. There were no serious drug-related adverse effects reported during the study.
"The difference in A1c trajectory during this 6-month study was remarkable, considering the study was conducted in nondiabetic subjects," Dr. Aronne told meeting attendees.
"Moreover, the primary driver for the difference [between active treatment and placebo] was a worsening of A1c levels in placebo-treated subjects that was arrested over the course of the study in subjects treated with VI-0521."
"The drug lowers A1c in diabetic patients, and for patients who haven't been diagnosed with diabetes, [it] can prevent increases in A1c levels," Dr. Aronne said. He predicted that "the next generation of diabetes medications will focus on weight-loss drugs" rather than solely on drugs that manage insulin sensitivity or resistance.
"One of the biggest problems of type 2 diabetes is obesity, which leads to a whole host of other problems — heart disease, joint problems, and metabolic problems," noted R. Paul Robertson, MD, ADA's president of medicine and science and an endocrinologist at Swedish Medical Center in Seattle, Washington, in an interview with Medscape Diabetes & Endocrinology after Dr. Aronne's presentation.
"We need to treat obesity aggressively, and that could resolve a lot of these other problems. An effective drug would be preferable to bariatric surgery, which is about the best option we have at the moment," Dr. Robertson said.
Phase 3 clinical trials of VI-0521 for the treatment of obesity are scheduled to be completed by the end of this year, and phase 2 trials for the treatment of type 2 diabetes are expected to conclude within the next year.
This study was study funded by Vivus. Dr. Aronne reports financial relationships with Amylin, Arena Pharmaceuticals, Orexigen Therapeutics, Sanofi-Aventis, and Vivus. Dr. Robertson receives support from Merck & Co.
American Diabetes Association (ADA) 69th Scientific Sessions: Abstract 119-OR. Presented June 8, 2009.
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Cite this: ADA 2009: New Weight-Loss Drug Stops Progression Toward Type 2 Diabetes - Medscape - Jun 15, 2009.