Orlistat does not improve insulin sensitivity independent of weight loss - Weight Loss

Nutrition Research Newsletter, Feb, 2004

It has been shown that diet composition influences insulin sensitivity independent of body weight. Diets with a high fat content seem to impair insulin sensitivity more than high-carbohydrate, low-fat diets do. However, not all fats impact insulin sensitivity in the same way. It appears that decreasing the proportion of saturated fatty acids (SFAs) and increasing that of mono-unsaturated fatty acids (MUFAs) improves insulin sensitivity, although, the underlying mechanism is unknown. Orlistat, a weight loss medication that inhibits gastric and pancreatic lipases, has also been shown to alter the proportion of fatty acids in serum triacylglycerols. The inhibition of fat absorption with the use of orlistat has been associated with a greater improvement in insulin sensitivity than has the use of placebos.

In order to ascertain whether orlistat has weight loss-independent effects on insulin sensitivity or body composition in obese women with a history of gestational diabetes (a risk factor for developing type 2 diabetes), a double-blind, placebo-controlled study was conducted. The aim was to achieve 8% weight loss over a similar period in women taking orlistat and in those taking a placebo. Forty-seven obese women were randomly assigned to receive either orlistat (120 mg 3 times per day; n = 23) or placebo (n = 24) with a hypocaloric diet. Whole-body insulin sensitivity (insulin clamp technique), serum fatty acids, and body composition (magnetic resonance imaging) were measured before and after weight loss.

The two groups did not differ significantly at baseline in regard to age, body weight, intra-abdominal and subcutaneous fat volumes, or insulin sensitivity. Weight loss did not differ significantly between the orlistat (7.3 kg [ or -] 0.2 kg, or 8.3% [ or -] 0.1%) and placebo (7.4 kg [ or -] 0.2 kg, or 8.2% [ or -] 0.1%) groups. Insulin sensitivity improved significantly (P < 0.001) after weight loss in the orlistat (from 4.0 [ or -] 0.3 mg x kg fat-free [mass.sup.-1] x [min.sup.-1] to 5.1 [ or -] 0.3 mg x kg fat-free [mass.sup.-1] x [min.sup.-1]) and placebo (from 4.4 [ or -] 0.4 mg x kg fat-free [mass.sup.-1] x [min.sup.-1] to 5.4 [ or -] 0.4 mg x kg fat-free [mass.sup.-1] x [min.sup.-1]) groups. Intra-abdominal fat and subcutaneous fat decreased significantly in both groups, but the ratio of these two decreased significantly only in the orlistat group. The proportion of dihomo-a-linolenic acid (20:3n-6) in serum phospholipids was inversely related to insulin sensitivity both before (r=-0.48, P<0.001) and after (r = -0.46, P < 0.001) weight loss, but it did not change significantly in either group.

It appears that weight loss, rather than the inhibition of fat absorption, improves insulin sensitivity. A decrease in fat absorption caused by orlistat does appear to favorably influence the ratio between intra-abdominlal and subcutaneous fat.

M. Tiikkainen, R. Bergholm, A. Rissanen, et al. Effects of equal weight loss with orlistat and placebo on body fat and serum fatty acid composition and insulin resistance in obese women. Am. J. Clin. Nutr. 79:22-30 (January 2004) [Correspondence: H Yki-Jarvinen, Department of Medicine, University of Helsinki, P.O. Box 340, FIN-00029 HUCH, Helsinki, Finland E-mail: ykijarvi@helsinki.fi.]