Phentermine/topiramate combo helps type 2 diabetes patients lose weight, control glucose

Obese and overweight patients with type 2 diabetes lost more weight and had better glycemic control when treated with phentermine/topiramate extended-release medication than with placebo, 2 industry-funded studies reported.

In a randomized, double-blind, phase 2 study, 130 patients were randomized to receive either placebo or active treatment of 15 mg of phentermine (PHEN) in the morning followed by 100 mg of topiramate (TPM) in the afternoon. There was a 4-week titration followed by 24 weeks of treatment. Patients were 18 to 70 years old with chronic, moderate to severe type 2 diabetes controlled by diet or oral antidiabetic medications. Patients who completed the first 28 weeks of the study were eligible to continue for an additional 28 weeks in their assigned treatment group; however, the active treatment group switched to an extended-release capsule combining 15 mg of PHEN and 92 mg of TPM, taken once each morning. The main outcome was change in HbA1c level at 56 weeks; secondary outcomes included percentage of weight lost and changes in use of concomitant diabetes medications. Patients in both groups also made lifestyle modifications.

Patients in the active treatment group reduced their mean HbA1c level by 1.6% compared to 1.2% in the placebo group (P=0.0381). Fifty-three percent of PHEN/TPM patients achieved an HbA1c goal of ≤7.0% compared with 40% of placebo patients (P<0.05). The treatment group also had significantly greater improvements in fasting glucose levels than the placebo group (−2.3 mmol/L vs. −1.5 mmol/L; P<0.05). The treatment group had a mean weight loss of 9.6% versus 2.6% with placebo (P<0.0001). At week 56, 65% of the active treatment group had lost at least 5% of their body weight compared to 24% in the placebo group. PHEN/TPM patients were more likely to decrease their number of antidiabetic medications taken during the study, as well (18.7% vs. 5.5%).

Researchers also performed a post hoc analysis of a subpopulation of 388 patients with type 2 diabetes from a separate study, CONQUER. One hundred fifty-seven patients were randomized to placebo, 164 received the 15-mg/92-mg PHEN/TPM combination, and 67 received a 7.5-mg/46-mg PHEN/TPM combination. Patients in both groups made lifestyle modifications. Seventy-five percent of patients completed all study visits. PHEN/TPM patients saw greater reductions in body weight and HbA1c values and were more likely to achieve HbA1c targets than placebo patients (P<0.05 for all); they also had greater reductions in antidiabetic medications.

The PHEN/TPM extended-release drug was generally well tolerated, the researchers noted, and the degree of weight loss in the active treatment groups met or exceeded the 5% to 7% goal recommended by the American Diabetes Association for type 2 diabetes patients. Study limitations include the fact that patients got lifestyle modification as well as drug treatment, which makes it more difficult to isolate the direct cause of changes. Also, patients had active management of care, so changes in the use of concomitant medications may have affected related study variables and masked true clinical differences, the researchers noted. “However, active management was applied consistently by treatment-blinded clinicians across placebo and PHEN/TPM [extended-release] treatment groups in an effort to approximate real-world clinical practice,” they added.

The studies were published online Sept. 23 by Diabetes Care. Funding for the studies was provided by VIVUS, Inc.