Weight loss drug reported to reverse diabetes
An investigational weight loss drug was reported to reverse type 2 diabetes; the results were presented at the International Diabetes Federation World Diabetes Congress 2011 (December 4-8; Dubai, United Arab Emirates) The medication, which has the proposed name Qnexa, was rejected by the US Food and Drug Administration (FDA) last year. Qnexa is a controlled-release combination of phentermine, an appetite suppressant, and topiramate, an anticonvulsant. "We need more options to treat the twin epidemics of diabetes and obesity," said Nancy J.V. Bohannon, MD, director of clinical research in the cardiovascular risk reduction program at St. Luke's Hospital (San Francisco, California), who presented the findings. She noted, "This could potentially be an approach that is nonsurgical for treating obesity and improving glycemic control." Dr. Bohannon, who is a consultant to, serves on the advisory board of, and holds stock in Vivus (Mountain View, California), the company that manufactures the drug.
In a subanalysis of the previously published CONQUER trial, researchers examined the effect of two different doses of the drug on 146 adults with type 2 diabetes and a body mass index (BMI) of 35 kg/m² or higher. The mean BMI of participants was 39 to 40 kg/m², the mean duration of their diabetes was four years, 65% were female, and diabetes treatment in the group included diet and exercise, with about 50% using the antidiabetic drug metformin.
The subjects were randomized to receive 52 weeks of placebo (58 patients), a half dose daily of the study drug (phentermine 7.5 mg/topiramate 46 mg; 24 patients), or a full dose daily (phentermine 15 mg/topiramate 92 mg; 64 patients).
At the end of the study period, subjects on the lower dose medication had a weight loss of 6.6%, while those on the higher dose had a 12.1% weight loss; weight loss in the placebo group was 2.8%. The investigators measured the drug's impact on excess weight, defined as the amount of weight above an ideal BMI of 25 kg/m². Compared with the placebo group, who lost 7.4% of their excess weight, subjects on the lower medication lost 17.8% and those on the higher dose lost 32.6%.
"Fasting blood sugar and hemoglobin A1c [a measurement of diabetes] showed statistically significant changes from baseline at the full dose," said Dr. Bohannon; however, she did not elaborate.
Resolution of diabetes, defined as the absence of clinical and laboratory manifestations of diabetes was seen in 1.7% of subjects in the placebo group, 8.3% of those on the loser dose of the medication, and 15.4% of those on the higher dose.
Dr. Bohannon noted that the most common adverse events included constipation, paresthesia (tingling sensation on the skin), insomnia, dry mouth, headache, and dysgeusia (distortion of the sense of taste).
With the FDA’s rejection of the medication, the use of the drug is controversial. The FDA's major reasons for rejecting the drug were teratogenicity and elevated heart rate. (Teratogenicity is a drug’s ability to develop genetic abnormalities in a developing fetus.) Other reasons cited by the FDA were metabolic acidosis (acidic blood), depression, anxiety, and sleep disorders, as well as attention, memory, language, and other cognitive disorders.
Dr. Bohannon noted that an excess weight loss of 32.6% was comparable to that attained by a laparoscopic gastric (stomach) banding procedure for the treatment of obesity. A recent study reported a 32% weight loss in diabetic subjects one year after gastric banding; another study reported a 47% loss two years after surgery.
"These are promising results. The question is: Will they be able to show enough safety so the FDA will be comfortable enough to approve it? The hope is that they will," said Francine Ratner Kaufman, MD, professor of pediatrics at the Keck School of Medicine, University of South California (USC), and head of the Center for Diabetes, Endocrinology and Metabolism at the Children's Hospital Los Angeles, who co-chaired the session. She added, "It will be part of the armamentarium of all the potential options for treating obesity and its comorbidities. I am a pediatrician, so it would be one of my last options, but certainly as a diabetologist, I am excited about as many options as possible."