Orlistat and effects on glycaemia

• orlistat is a lipase inhibitor that alters the absorption of fat through the gastrointestinal (GI) tract
  • results in the excretion of approximately 30% of ingested fat - thus reducing the calorie intake of the patient
  • studies have demonstrated that orlistat is clinically beneficial in reducing body weight and co-morbid risk factors in patients with Type 2 diabetes treated concomitantly with oral hypoglycaemic medications (1,2,3)
    • orlistat and effects on glycaemia
      • the XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) study revealed that orlistat can also delay or prevent the development of Type 2 diabetes in high-risk patients (4)
      • use of orlistat in newly diagnosed type 2 diabetics not receiving oral hypoglycaemic agents
        • a study investigated evaluated the efficacy of 24 weeks’ treatment with orlistat, combined with a mildly reduced-calorie diet, on weight loss and glycaemic control in overweight and obese patients with newly diagnosed and previously untreated Type 2 diabetes (5)
          • study results revealed that orlistat-treated patients achieved a significantly greater decrease in fasting plasma glucose (-1.3 vs. -0.5 mmol/l; P = 0.0003) and in the 2-h oral glucose tolerance test (-4.1 vs. -1.4 mmol/l; P < 0.0001) than placebo recipients
          • a significant decrease in HbA1c from baseline was obtained with orlistat (-1.0 vs. -0.6%; P = 0.0008)
      • various studies have revealed the glycaemic benefits of using orlistat in patients with type 2 diabetes (1,2,3)
        • use of orlistat in patients already treated with maximal metformin and sulphonylyurea treatment (3) was investigated in a small study
          • total of 60 female type 2 diabetic patients with BMI > 25 kg/m2 and glycosylated haemoglobin (HbA1c) > 8% were assigned to two groups. In addition to their maximal doses of sulphonylureas (gliclazide (320 mg/day) or glipizide (20 mg/day)) and metformin (2000 mg/day), one group (n = 30) received a placebo and the other (n = 30) received orlistat (120 mg t.i.d.) for 12 weeks
            • study results revealed that mean fasting insulin levels decreased more in the orlistat group than in the placebo group (28.8 ± 3.0 vs. 2.4 ± 1.2 pmol/l; p < 0.01)
            • mean HbA1c values dropped by 1.7 ± 0.01% (p < 0.05) in the orlistat group, but remained unchanged in the placebo group
      • based on the glycaemic lowering effects of orlistat seen in studies, orlistat was classified as an oral hypoglycaemic agent in Canada in 2003 (6)

Reference:

• (1) Hollander PA et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study. Diabetes Care 1998; 21: 1288-1294.
• (2) Hanefeld M et al The effects of orlistat on body weight and glycaemic control in overweight patients with type 2 diabetes: a randomized, placebo-controlled trial. Diabetes Obes Metab 2002; 4: 415- 423.
• (3) Kuo CS et al. Effect of orlistat in overweight poorly controlled Chinese female type 2 diabetic patients: a randomised, double-blind, placebo-controlled study.Int J Clin Pract. 2006 Aug;60(8):906-10.
• (4) Torgerson JS et al. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004; 27: 155-161
• (5) Shi YF et al. Orlistat in the treatment of overweight or obese Chinese patients with newly diagnosed Type 2 diabetes.Diabet Med. 2005 Dec;22(12):1737-43.
• (6) Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, Canadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada, Can. J. Diabetes 2003;27 (Suppl. 2): S1–S152.