Effects of Weight Loss With Orlistat on Glucose Tolerance and Progression to Type 2 Diabetes in Obese Adults

University of Helsinki, Helsinki, Uusimaa, Finland
Archives of Internal Medicine (Impact Factor: 17.33). 05/2000; 160(9):1321-6. DOI: 10.1001/archinte.160.9.1321
Source: PubMed


Orlistat is a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, promotes weight loss, and may reduce the risk of developing impaired glucose tolerance and type 2 diabetes in obese subjects.
To test the hypothesis that orlistat combined with dietary intervention improves glucose tolerance status and prevents worsening of diabetes status more effectively than placebo.
We pooled data from 675 obese (body mass index, 30-43 kg/m2) adults at 39 US and European research centers in 3 randomized, double-blind, placebo-controlled multicenter clinical trials. Subjects received placebo plus a low-energy diet during a 4-week lead-in period. On study day 1, the diet was continued, and subjects were randomized to receive placebo 3 times a day (n=316) or treatment with orlistat, 120 mg 3 times a day (n=359), for 104 weeks. A standard 3-hour oral glucose tolerance test was performed on day 1 and at the end of treatment.
The categorical assessment of glucose tolerance status (normal, impaired, diabetic) and changes in status from randomization to end of treatment were the primary efficacy measures. The secondary measures were fasting and postchallenge glucose and insulin levels.
The mean length of follow-up was 582 days. Subjects who were treated with orlistat lost more weight (mean +/- SEM, 6.72 +/- 0.41 kg from initial weight) than subjects who received placebo (3.79+/-0.38 kg; P<.001). A smaller percentage of subjects with impaired glucose tolerance at baseline progressed to diabetic status in the orlistat (3.0%) vs placebo (7.6%) group. Conversely, among subjects with impaired glucose tolerance at baseline, glucose levels normalized in more subjects after orlistat treatment (71.6%) vs placebo (49.1%; P=.04).
The addition of orlistat to a conventional weight loss regimen significantly improved oral glucose tolerance and diminished the rate of progression to the development of impaired glucose tolerance and type 2 diabetes.

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    • "Therefore, further investigation is needed about the effects of anti-lipase IgY treatment for longer period on the body weight gain and obesity-induced metabolic disorders, in future. However, a specific pancreatic lipase inhibitor, Orlistat, has been used in clinics for the prevention of obesity [2], and Orlistat has been shown not only to prevent body weight gain but also to improve obesity-induced metabolic disorders, such as glucose intolerance and diabetes [32]. Our results showed that anti-lipase IgY has more potent inhibitory effect on the pancreatic lipase than Orlistat (IC50 values: 0.49 μM vs 0.96 μM) [17]. "
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    ABSTRACT: There is completely no report about both hen egg anti-lipase immunoglobulin yolk (IgY) and its anti-obesity action. Thus, we tried to isolate and characterize a novel anti-lipase immunoglobulin from hen egg yolk. Moreover, we investigated whether hen egg yolk anti-lipase IgY inhibits pancreatic lipase activity in vitro, and examined its ability to prevent obesity in a murine high fat diet-induced obesity model. We determined the inhibitory action of Anti-lipase IgY on lipase activity in vitro. We also focused our evaluation on the anti-obesity properties of Anti-lipase IgY in a murine high fat diet-induced obesity model. Anti-lipase IgY blocked porcine lipase activity with an IC50 of 0.49 muM. Supplementing the high fat diet with only 0.2% (w/w) of Anti-lipase IgY for 35 days significantly decreased the weights of intraperitoneal adipose tissues, epididymal, mesenteric, retroperitoneal and perirenal adipose tissues, and the amounts of hepatic total lipid, triglyceride, and cholesterol. This was accompanied by a significant increase in the fecal excretion of triglyceride in the absence of diarrhea. Furthermore, Anti-lipase IgY treatment restored body weight gain to levels similar to mice fed with Control IgY. This study provides the first report of the development of anti-lipase IgY and the direct evidence that inhibition of pancreatic lipase using Anti-lipase IgY is an effective anti-obesity treatment due to the associated increase in fecal excretion of triglyceride.
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    • "Beneficial renal effects, like reduction of glomerular hyperfiltration and albuminuria, have been demonstrated after weight loss (either through diet or bariatric surgery) [105] [155], although these results still need to be demonstrated by properly designed clinical trials. Additionally, the impact on renal outcomes resulting from improved insulin resistance through pharmacologic weight loss [156] or the Mediterranean diet [157] has not been studied. Moreover, in light of what is known about renal hemodynamics (see above), the safety of the so popular " high-protein lowcarbohydrate " weight reduction diet should also be analyzed. "
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    ABSTRACT: The metabolic syndrome (MS) and chronic kidney disease (CKD) have both become global public health problems, with increasing social and economic impact due to their high prevalence and remarkable impact on morbidity and mortality. The causality between MS and CKD, and its clinical implications, still does remain not completely understood. Moreover, prophylactic and therapeutic interventions do need to be properly investigated in this field. Herein, we critically review the existing clinical evidence that associates MS with renal disease and cardiovascular disease, as well as the associated pathophysiologic mechanisms and actual treatment options.
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    • "An initial effort to state that anti-obesity drugs could prevent T2DM was a multicenter evaluation of orlistat, a pooled post hoc analysis (n = 675 obese adults with impaired glucose tolerance treated for a men follow-up of 582 days) of three randomized, placebo-controlled clinical trials (Heymsfield et al 2000). Obese nondiabetic individuals received either orlistat (120 mg three times a day with food) or placebo for two years, combined with a mild low energy diet. "
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    ABSTRACT: There has been an increase in the concern about preventing type 2 diabetes mellitus (T2DM), a disease with great and increasing prevalence. The prevalence of obesity, physical inactivity, Western processed diet, important risk factors for the development of T2DM, are also rising. Free fatty acids are increased in obesity and reduce insulin clearance and increase hepatic glucose production. Implementation of a healthy lifestyle has been show to slow the progression of impaired glucose tolerance to T2DM. Orlistat is an inhibitor of lipase activity, with proved efficacy in body weight reduction and long-term management of obesity and more favorable effects on carbohydrate metabolism and it was prospectively shown in XENDOS study that orlistat promoted long-term weight loss and prevented T2DM onset in obese individuals with normal and impaired glucose tolerance at baseline over four years. This benefit could be associated to the weight loss itself, to the limited absorption of lipids and reduction of plasma free fatty acids, to increased production of incretins or to modulation of secretion of cytokines by adipocytes, all effects secondary to orlistat treatment. A proposed strategy is to identify subjects at highest risk to receive a drug intervention, using lifestyle interventions alone at the community level.
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