nateglinide and Weight-Gain

The complications of diabetes mellitus, arising from inadequate glycemic control, have serious consequences for society as well as individuals. It is now urged that tight glycemic control be the goal for all patients, regardless of type of diabetes. Unfortunately, hypoglycemia can be a consequence of this aggressive approach. Treatment with a combination of agents and improved therapies are needed to maintain glycemic balance in patients. A better understanding of the pathophysiology of diabetes has yielded many treatment options based on various mechanisms of action. The sulfonyluereas, repaglinide, metformin, acarbose and the thiazolidinediones are effective in decreasing fasting plasma glucose levels, but their limitations may include adverse effects, such as weight gain and hypoglycemia, and an inability to modify some of the important comorbidities of diabetes. Therapies aimed at treating mealtime hyperglycemia are gaining attention. One promising investigational agent in this category is nateglinide. Early data suggest that its rapid onset and short duration of action result in increased early mealtime insulin release, reduced mealtime glucose excursions, and improved glycemic control.

Topics: Acarbose; Administration, Oral; Blood Glucose; Carbamates; Cyclohexanes; Diabetes Mellitus, Type 2; Drug Combinations; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Insulin-Secreting Cells; Metformin; Nateglinide; Phenylalanine; Piperidines; Randomized Controlled Trials as Topic; Thiazolidinediones; United States; Weight Gain

The respiratory quotient (RQ) is useful for evaluating glucose and lipid metabolism in vivo. We previously reported that the RQ value, even after fasting, was high in diabetics being treated with sulphonylurea (SU), which might explain the accumulation of fat, leading to weight gain in such individuals. In the present study, we measured the RQ in type II diabetic patients who were being treated with a rapid-onset/short-duration insulinotropic agent, nateglinide, and compared it with those being treated with SU.. A glucose tolerance test was performed in 20 patients with type II diabetes mellitus treated with nateglinide and in 14 patients treated with SU, and the RQ was simultaneously measured.. The RQ values in the patients treated with nateglinide, were similar to those in healthy adults, but was lower than in those treated with SU. No weight gain was observed in patients treated with nateglinide.. A significant weight gain was reported in subjects treated with SU, accompanied by an increase in RQ. However, weight gain was less frequent in diabetics treated with nateglinide.

Topics: Aged; Blood Glucose; Body Weight; Cyclohexanes; Diabetes Mellitus, Type 2; Female; Glyburide; Humans; Hypoglycemic Agents; Insulin Resistance; Lipid Metabolism; Lipids; Male; Middle Aged; Nateglinide; Phenylalanine; Weight Gain