orlistat and Hyperglycemia

Obesity is a global epidemic with important healthcare and financial implications. Most current antiobesity pharmacological therapies are unsatisfactory due to undesirable side effects. Many drugs have been withdrawn due to safety concerns. Maintaining weight loss remains the Achilles' heel of antiobesity therapy.. This is an overview of the use of liraglutide for obesity treatment. Clinical efficacy on weight, cardiovascular parameters, as well as safety and tolerability issues are discussed.. Liraglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist, which has a protracted pharmacokinetic profile compared to native GLP-1 while maintaining its biological activity. It induces weight loss by reducing appetite and energy intake. It stimulates insulin release and decreases glucagon secretion in response to hyperglycaemia. Treatment with liraglutide, in addition with diet and exercise, induces sustained mean weight loss of 7.6 kg at 2 years (weight loss induced by orlistat = 5.7 kg, phentermine/topiramate controlled release 15/92 = 10.9 kg). It reduces blood pressure and improves glycaemic control, which has clinically relevant significance on reducing obesity-related morbidity and mortality. Liraglutide is reasonably well tolerated with gastrointestinal side effects being most commonly encountered. Novo Nordisk filed for regulatory approval of liraglutide 3.0 mg for obesity treatment in December 2013.

Topics: Animals; Anti-Obesity Agents; Blood Glucose; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hyperglycemia; Hypoglycemic Agents; Lactones; Liraglutide; Obesity; Orlistat; Receptors, Glucagon; Treatment Outcome; Weight Loss

Glucagon-like peptide-1 is an insulin secretion-stimulating gut hormone that is produced in response to food intake. Orlistat (Xenical, F. Hoffman-La Roche, Basel, Switzerland), which decreases fat absorption and increases intestinal fat content, may therefore affect the secretion of glucagon-like peptide-1. In this study we examined the immediate effects of orlistat on postprandial serum glucose, insulin and glucagon-like peptide-1 levels prior to a change in body weight.. Randomized, clinical study.. Sixteen nondiabetic obese patients (body mass index 35.7 +/- 3.8 kg/m(2), range 32.5-43.1) were enrolled in this study. The patients were randomly assigned to either the group treated with orlistat (120 mg, single dose) or the control group. There were eight patients in each of the two groups. Orlistat was given before a standard 600-kcal mixed meal containing 60% carbohydrates, 25% lipids and 15% protein. Blood samples were collected at baseline and at 30-min intervals for 180 min after the test meal. Graphical tendencies, peak value, time to reach the peak value, and area under the curve in the two groups were compared.. Blood samples were obtained for the measurement of GLP-1, glucose, insulin, high density lipoprotein, total cholesterol and triglycerides.. We found no difference in sex distribution, mean age, anthropometric measurements, or baseline glucose, insulin and glucagon-like peptide-1 levels between the orlistat and placebo groups. The peak insulin and glucagon-like peptide-1 levels were determined at 60 min in the control group. Hourly changes in serum glucose and insulin levels were similar between the groups, although the peak insulin and glucagon-like peptide-1 levels were reached at 120 min in the orlistat group. There were no statistically significant differences between the groups.. A single dose of 120-mg orlistat caused no change in postprandial serum glucose, insulin or glucagon-like peptide-1 levels in nondiabetic obese patients. Although glucagon-like peptide-1 increases were delayed in the orlistat group, these changes were nonsignificant.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Diabetes Mellitus; Female; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Insulin; Lactones; Male; Middle Aged; Obesity; Orlistat

Topics: Adult; Anti-Obesity Agents; Chronic Disease; Clozapine; Humans; Hyperglycemia; Lactones; Male; Obesity; Orlistat; Schizophrenia