Active Ingredient: Orlistat
In 1 study the reduction was 6. Orlistat 120 mg 3 times daily was significantly more effective than placebo also given in conjunction with a hypocaloric diet in these studies.
During the second year of treatment, when patients were switched from a hypocaloric diet to a eucaloric diet, orlistat recipients regained significantly less weight than placebo recipients. Orlistat appears to improve lipid profiles in non-diabetic obese patients, reducing levels of total cholesterol and low density lipoprotein cholesterol.
In a study of patients with obesity associated with type 2 diabetes, patients treated with orlistat lost more weight and had improved serum lipid profiles compared with placebo recipients. Similarly in humans, extreme changes in the ratio of fat to carbohydrate modulate insulin sensitivity, whereas smaller changes, which are more feasible in daily life, appear to have no effect on insulin sensitivity 2.
More promising results regarding the possibility of enhancing insulin action via changes in diet were achieved by altering the composition of dietary fat.
In animals, diets containing saturated fat impair insulin action more than do isocaloric diets enriched with monounsaturated and polyunsaturated fatty acids MUFAs and PUFAs, respectively; 1.
The mechanism underlying these changes is unclear. One possibility is that incorporation of SFAs into membrane phospholipids of insulin-sensitive tissues such as skeletal muscle impairs insulin action 4.
It was also shown to alter the proportion of fatty acids in serum triacylglycerols, cholesterol esters, and phospholipids 14.
Weight loss is accompanied by loss of both subcutaneous and visceral fat and by improved insulin sensitivity 15 — 20.
Inhibition of fat absorption with the use of orlistat has been associated with greater improvement in insulin sensitivity than has the use of placebo 21 — 23, but it is unclear whether these beneficial metabolic effects are specific to orlistat or are secondary to a hypocaloric diet and weight loss: in studies reporting data on serum insulin concentrations, weight loss has been greater in the orlistat group than in the placebo group 21 — 23.
In a placebo-controlled study including 523 subjects with initially normal glucose tolerance, orlistat decreased serum insulin and glucose concentrations during an oral-glucose-tolerance test, and this treatment effect remained significant even after adjustment for changes in body weight between the orlistat and placebo groups 23.
These data thus suggested that orlistat improved insulin sensitivity independent of body weight.
In an uncontrolled study involving 6 patients, orlistat was found to improve insulin sensitivity, which was measured with the use of the euglycemic insulin clamp technique, independent of changes in body weight 24.
In the present study, we wished to ascertain whether orlistat has weight loss—independent effects on insulin sensitivity or body composition in obese women with a history of gestational diabetes, which increases the risk of developing type 2 diabetes 25.
Insulin sensitivity was measured by using the euglycemic insulin clamp technique, and body composition was measured by using magnetic resonance imaging.
To determine whether orlistat modified fatty acid composition as expected on the basis of previous studies 14, 26, we measured the composition of fatty acids in serum phospholipids by gas chromatography.
A 2-h oral-glucose-tolerance test with 75 g glucose was performed to exclude women with diabetes 27. A total of 57 women who met the inclusion and exclusion criteria were included in the study. In each woman, insulin sensitivity measured by using the euglycemic hyperinsulinemic clamp technique, intraabdominal and subcutaneous fat measured by using magnetic resonance imaging, and waist-to-hip ratio were measured before and after weight loss as detailed below.
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