June 19, 2010
2 min read

Dramatic weight loss benefits with combination phentermine, topiramate

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The Endocrine Society 92nd Annual Meeting

SAN DIEGO — A low-dose, once-daily, controlled-release formulation of phentermine plus topiramate reduced weight and produced additional metabolic benefits in overweight and obese patients after 56 weeks, new data indicate.

“Phentermine and topiramate have been demonstrated to cause weight loss through different mechanisms, and we have seen a greater response from the combination of the two than in just one, which allows for lower doses of each agent,” W. Timothy Garvey, MD, professor and chair of the department of nutrition sciences at University of Alabama at Birmingham, said at a clinical trials symposium.

The multicenter, phase 3 study included 2,500 overweight (BMI, 27 to 45) patients with two or more metabolic comorbidities, including dyslipidemia, dysglycemia and hypertension. Garvey and colleagues randomly assigned patients in a 2:1:2 ratio to receive placebo (n=994), phentermine 7.5 mg plus topiramate 46 mg (n=498) or phentermine 15 mg plus topiramate 92 mg (n=995).

At week 56, mean percent weight loss was significantly greater among patients assigned to combination therapy (Qnexa, Vivus) compared with placebo. The placebo group recorded a 1.2% loss, the low-dose group a 7.8% loss and the high-dose group a 9.8% loss (P<.0001), using intention-to-treat, last observation carried forward data.

Significant, dose-related improvements in lipids, glycemic parameters and insulin sensitivity were observed in the phentermine plus topiramate group in a secondary analysis for cardiometabolic risk factors. These improvements were significantly greater than those observed in the placebo group, except for the decrease in LDL only in the low-dose combination therapy group.

Patients assigned to phentermine plus topiramate also had greater mean improvements in adiponectin, C-reactive protein and fibrinogen vs. placebo.

Thus, combination therapy also improved cardiometabolic risk factors known to increase the risk for type 2 diabetes and cardiovascular disease. Further, the greater weight loss recorded with high-dose phentermine plus topiramate was associated with the greatest improvements in cardiometabolic risk factors.

Both doses of phentermine plus topiramate were well tolerated, and therapy was associated mild adverse events.

“The complementary mechanisms [of the two drugs] may counter each agent’s side effects,” Garvey said. – by Matthew Brannon


I was extremely interested to see the data from this study after reading the initial phase 2 results a couple of years ago. Any option available that can help to improve our patients’ ability to experience weight loss as well as improve their metabolic parameters is exciting. The only question is the issue of hypertension, but drawing from Dr. Garvey's presentation it appears that blood pressure was stable and even slightly decreased. With this combination of phentermine and topiramate we have much lower doses, and far more dramatic weight losses, which is promising.

Carol H. Wysham, MD

Assistant Clinical Professor of Medicine at the University of Washington School of Medicine,
Section Head of the Department of Endocrinology at Rockwood Clinic in Spokane, Wash.

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