Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes.
Derosa G, Cicero AF, D'Angelo A, Fogari E, Maffioli P.
Clin Pharm Ther. 2011 Aug 4.
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
Department of Internal Medicine, Aging and Kidney diseases, "G. Descovich"
Atherosclerosis Study Center, University of Bologna, Bologna, Italy.
The behavioural approach is usually slow and not known and not always sufficient to achieve optimal targets in weight and metabolic control in obese diabetic patients, and a pharmacological treatment is often necessary. The aim of this study was to compare the effects of orlistat and placebo on body weight, glycaemic and lipid profile and insulin Two hundred and resistance in patients with type 2 diabetes.
Fifty-four obese, diabetic patients were enrolled in this study and randomized to take orlistat. We evaluated at baseline and after 3, 6, mg or placebo for 1, 3, and 6 months body weight, waist circumference (WC), body mass index 9 and 12 (BMI), glycated haemoglobin (HbA(1c) ), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), lipid profile, retinol-binding protein-4 (RBP-4), resistin, visfatin and high-sensitivity C-reactive protein (Hs-CRP). Results and Discussion: We observed a significant reduction in body weight, WC, BMI, lipid profile, RBP-4 and visfatin in the orlistat group but not in control group. Faster improvements in HbA(1c) , PPG, FPI, HOMA-IR, resistin and Hs-CRP were recorded with orlistat than with placebo. A similar decrease in FPG was seen in the two groups. Significant predictors of change in insulin resistance (HOMA-IR) were RBP-4 and resistin concentration in the orlistat -0·53, P = group (r< -0·59, P = 0·05, and r <0·01, respectively).
This is the first study investigating the effect of orlistat on insulin resistance and markers of inflammation. Orlistat improved lipid profile and led to faster glycaemic control and insulin resistance parameters than the control, without any serious adverse event. Orlistat also improved RBP-4 and visfatin, effects not observed with placebo.
Obesity: Orlistat 60 mg reduces levels of visceral adipose tissue in obese individuals.
Adherence to weight loss medications; post-marketing study from HMO pharmacy data of one million individuals.
Hemo B, Endevelt R, Porath A, Stampfer MJ, Shai I.
Nat Rev Gastroenterol Hepatol. 2011 Sep 2
Franks I. Diabetes Res Clin Pract. 2011 Sep 8.
Research and Evaluation Unit, Maccabi Healthcare Services, Tel-Aviv, Israel.
Post-marketing data on weight-loss medications in free living population are a necessary adjunct to data from clinical trials.
MATERIALS AND METHODS:
We conducted a population-based analysis of first-time medication users based on HMO pharmacy purchasing data serving>one million adults.
During 5 years, usage of orlistat and sibutramine more than doubled and rates were higher during the months May-Aug. As compared to non-users (n=1,038,828), annual weight-loss drug users (n=7175) had higher women proportion, body-mass-index (BMI), bariatric surgery history, and usage of diabetes, depression, and cardiovascular medications (p<0.001 for all). Among users, men had higher BMI (34.4kg/m(2) vs. 32.5kg/m(2)), prevalence of diabetes (25.4% vs. 10.7%) and heart disease (14.2% vs. 3.5%) than women. Mean duration of purchasing weight-loss medications was 2.1 months for orlistat and 2.9 months for sibutramine. Fewer than 2% completed 12months of weight-loss medication therapy. Among the 25% who continued to purchase at least 4months, BMI (sub-group analysis) reduced from 33.02kg/m(2) to 32.04kg/m(2) (p<0.001). In a multivariate model, long-term adherence (≥4months) to weight-loss medications was associated with use of sibutramine vs. orlistat (OR=2.08; 95%CI: 1.76- 2.45), and prevalence of diabetes (OR=1.20; 95%CI: 1.01-1.25). Age, gender, and baseline BMI were not associated with long-term adherence.
Usage of weight-loss drugs is higher among diabetes patients. However, the poor adherence to therapy is substantially below levels reported in clinical trials.
Novel strategy for the use of leptin for obesity therapy.
Tam CS, Lecoultre V, Ravussin E.
Expert Opin Biol Ther. 2011 Sep 13
Human Physiology, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808 , USA +1 225 763 3186 ; +1 225 763 3030 ;email@example.com.
Obesity is a chronic disease and a major global health challenge. Apart from bariatric surgery, which is costly and not without risk, there are currently no successful long-term treatment options for obesity. The history of pharmacological agents for obesity has been turbulent with many examples of drugs being removed from the market due to significant side effects. Orlistat and sibutramine (the latest drugs on the market) provide only modest weight loss and are both associated with high attrition rates due to intolerable side effects. Furthermore, sibutramine was recently withdrawn from the market. There is a need for the development of safe and efficacious drug treatments for obesity.
This review covers the history of leptin therapy as an orphan drug, leptin-replacement therapy as a treatment for obesity, preclinical studies showing the efficacy of leptin/amylin combination and finally, the very promising early clinical findings using pramlintide/meteleptin combination therapy in overweight to obese individuals. Expert opinion: Combination pharmacological therapy, such as pramlintide/metreleptin, for the treatment of obesity is very promising and is supported by encouraging weight loss results and improvement in metabolic makers in early-phase clinical studies. However, the latest randomized clinical trial on pramlintide/metreleptin was recently stopped due to safety concerns.