Pramlintide Found Safe and Effective for Weight Loss in Obese Subjects With or W

PRAM-treated subjects completing 16 wks experienced progressive weight loss, with a 3.6kg reduction in body weight . In addition to its glucoregulatory effects in insulin-treated patients with diabetes, pramlintide (PRAM), an analog of the -cell hormone amylin, has shown various effects relevant to obesity in previous trials.

These include meal-related satiation, food intake reduction, and sustained weight loss in overweight/obese subjects with insulin-treated type 2 diabetes mellitus. This randomized, triple-blind, placebo (PBO)-controlled study assessed the safety, dose tolerance, and weight-related effects of PRAM, at doses &>120 g, in obese, non-insulin-treated subjects.

After a 1-wk PBO lead-in, 204 obese subjects (160 nondiabetic, 44 T2DM [metformin only], were randomized (2:1) to 16 wks of treatment with PRAM or PBO TID (4-wk dose escalation based on tolerability, 12-wk dose maintenance, no lifestyle intervention).

PRAM was well tolerated with 90% of subjects able to escalate to 240 g TID. No unexpected safety signals and no severe hypoglycemia were observed. The most common adverse event reported for PRAM vs. PBO was mild, transient nausea (36% vs. 22%).

PRAM-treated subjects completing 16 wks experienced progressive weight loss, with a mean SE PBO-corrected 3.6kg reduction in body weight .

Approximately 31% (vs. 2% PBO) of these subjects achieved 5% weight loss. The PBO-corrected weight loss with PRAM was observed in both nondiabetic and T2DM subjects (3.4and 3.7kg) and was most pronounced in subjects with a baseline BMI <35 kg/m2 and was accompanied by a reduction in waist circumference (3.4 cm).

PRAM-treated subjects who did not report nausea during the study experienced similar weight loss as those who did (3.5 0.5 and 3.6 0.7 %). These results provide additional insights into the safety and tolerability of PRAM and support further evaluation of PRAM as a potential treatment for obesity.

Christian Weyer, Ken Fujioka, Vanita Aroda, Steve Edelman, Kim Chen, Cameron Lush, Yan Wang, Colleen Burns, Karen Lutz, Shereen McIntyre, Jonathan Kornstein, Matthew Wintle, Alain Baron. Amylin Pharm, Inc, San Diego, CA; Scripps Clin, San Diego, CA; Univ of California, San Diego, San Diego, CA

ENDO 2005 POSTER SESSION: BASIC/CLINICAL – Obesity & Metabolic Syndrome I (11:00 AM-12:00 PM and 2:30 PM-3:30 PM)

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FACT: The coffee diterpene cafestol (CAF) is present in unfiltered coffee brews such as Scandinavian boiled, Turkish and cafetiere coffee. CAF is the most potent cholesterol-elevating compound known in the human diet. A study by Marie-Louise Ricketts of Baylor College of Medicine sought to determine whether CAF exerts its effects via nuclear hormone receptors that control genes involved in cholesterol homeostasis.

The data determined that CAF acts as an agonist ligand for both FXR and PXR, and this may contribute to its ability to raise cholesterol levels. CAF acts as a potential agonist ligand for both FXR and PXR, and this may contribute to its effect on cholesterol homeostasis.
ENDO 2005