Rimonabant: Time to SERENADE A New Oral Antidiabetic Agent?

Dr Julio Rosenstock (University of Texas Southwestern Medical School, Dallas), who presented SERENADE, said the issue of whether rimonabant should now be labeled an oral antidiabetic agent "was an issue of semantics." The new study met its primary objective, and the findings on HbA1c were "robust." "There was a lot of consistency with the RIO-Diabetes study, where blood-sugar control was a secondary end point," he noted.

He believes that rimonabant has "tremendous potential" in the treatment of diabetes. "Every time we improve diabetes control, we have a price to pay in terms of weight gain. But with rimonabant we see an improvement in HbA1c with important reductions in weight—that is what makes it different and distinct." Rimonabant also showed improvements in multiple cardiometabolic risk factors in the trial, and there is hope that it can be successfully combined with other antidiabetic drugs, he said.

Dr Nick Finer (University of Cambridge, UK) said: "SERENADE doesn't allow us to say yet that rimonabant is a primary treatment for diabetes, but I hope it will persuade general practitioners, when faced with overweight or obese diabetics, that they should be considering rimonabant as part of a wide variety of treatments they have to offer."

SERENADE was a multicenter, randomized, placebo-controlled study comparing rimonabant 20 mg once daily with placebo in improving blood-sugar control in treatment-naive type 2 diabetics not adequately controlled by diet alone for a period of six months. There were 278 patients enrolled at 56 study centers in the US, Germany, Argentina, Chile, Hungary, Poland, and the Netherlands.

At baseline, both the placebo and active-treatment groups had HbA1c levels of 7.9%, and by the end of six months of treatment, those receiving rimonabant had a significant 0.8% lowering of HbA1c from baseline, compared with 0.3% in the placebo group (p=0.002). In addition, those with levels of HbA1c of 8.5% or greater at baseline had "very robust" reductions of HbA1c with rimonabant, Rosenstock said—1.9% vs 0.7% with placebo (p<0.0009). These effects on HbA1c were accompanied by significant improvements in a range of other cardiometabolic risk factors, with the exception of blood pressure.

Approximately 57% of the improvements in HbA1c were independent of the weight loss achieved, said Rosenstock, "suggesting a direct pharmacologic effect of rimonabant" on blood sugar, he noted. He also applauded the reduction in waist circumference seen with rimonabant. "Every time you get your waist circumference down, you are potentially reducing cardiovascular events, and this is an important issue. This opens the door to a new approach addressing the multiple issues in diabetes."

But Rosenstock and other panel members present during the webcast reiterated that metformin is still the first choice of antidiabetic agent, as agreed in a consensus issued a few months ago by the American Diabetes Association and its European equivalent.

Nevertheless, metformin plus rimonabant—a combination used in RIO-Diabetes—should probably be the first-choice combination therapy in diabetes, Rosenstock said. Other combinations to be examined are rimonabant with glitazones, "which have a major problem with weight gain," DPP4 inhibitors, and even insulin itself, he added.

Rimonabant is currently available in several European countries, including the UK and Germany, as well as a few other markets, such as Argentina, for the treatment of obesity or overweight patients with associated risk factors, such as diabetes or dyslipidemia. In the US, however, approval has been slow in coming. At the end of October, Sanofi Aventis said it submitted a complete response to the FDA's approvable letter for rimonabant, which was issued in February.

Rosenstock R. International Diabetes Federation 19th World Diabetes Congress. December 3-7, 2006. Cape Town, South Africa.

==========================

Advertisement
Do you have patients in pain? Over 4,800 Anodyne Therapy Care Providers are increasing circulation and reducing pain for thousands of patients per month. To find out how you can help your patients get back to life, click here.
http://www.diabetesincontrol.com/annodyne/anodyne10_31_01.php