Alpha-glucosidase inhibitors and lipase inhibitors for treatment of diabetes mellitus
- David K McCulloch, MD
David K McCulloch, MD
- Clinical Professor of Medicine
- University of Washington
Two oral classes of drugs lower blood glucose by modifying the intestinal absorption of carbohydrates and fat: alpha-glucosidase inhibitors and lipase inhibitors. The pharmacology and use of these drugs will be discussed here. Other oral hypoglycemic drugs are reviewed separately. (See "Metformin in the treatment of adults with type 2 diabetes mellitus" and "Thiazolidinediones in the treatment of diabetes mellitus" and "Sulfonylureas and meglitinides in the treatment of diabetes mellitus".)
The alpha-glucosidase inhibitors (acarbose, miglitol, voglibose) have been studied extensively in Europe and Japan; two of them, acarbose and miglitol, are available in the United States. Taken orally, they inhibit the upper gastrointestinal enzymes (alpha-glucosidases) that convert complex polysaccharide carbohydrates into monosaccharides in a dose-dependent fashion. These drugs slow absorption of glucose; the slower rise in postprandial blood glucose concentrations is potentially beneficial in both type 1 and type 2 diabetes. In older patients with type 2 diabetes, acarbose may also increase insulin sensitivity .
In patients with type 1 diabetes, acarbose therapy decreases the amplitude of postprandial glycemic excursions and lowers glycated hemoglobin (A1C) values [2,3]. (See "Estimation of blood glucose control in diabetes mellitus".)
Acarbose and voglibose have also been evaluated for the prevention of type 2 diabetes. (See "Prevention of type 2 diabetes mellitus", section on 'Alpha-glucosidase inhibitors'.)
Efficacy — Several trials have demonstrated the efficacy of acarbose in patients with type 2 diabetes [4-6]. In one trial 96 patients who were inadequately controlled by diet alone were randomly assigned to receive either glyburide or acarbose . The A1C values and fasting blood glucose concentrations fell by a similar amount in both groups; postprandial blood glucose concentrations, however, remained high in the glyburide group but fell in the acarbose group. A second trial evaluated 354 patients treated with diet alone or diet plus a sulfonylurea, metformin, or insulin . As compared with placebo, the addition of acarbose in each of these groups reduced the mean postprandial blood glucose concentration by 63 mg/dL (3.5 mmol/L) and lowered A1C values by 0.4 to 0.9 percentage points; furthermore, more than 50 percent of patients responded to acarbose. In general acarbose has resulted in greater improvement in A1C values than in fasting blood glucose concentrations, consistent with its predominant effect on postprandial hyperglycemia .
- Meneilly GS, Ryan EA, Radziuk J, et al. Effect of acarbose on insulin sensitivity in elderly patients with diabetes. Diabetes Care 2000; 23:1162.
- Hollander P, Pi-Sunyer X, Coniff RF. Acarbose in the treatment of type I diabetes. Diabetes Care 1997; 20:248.
- McCulloch DK, Kurtz AB, Tattersall RB. A new approach to the treatment of nocturnal hypoglycemia using alpha-glucosidase inhibition. Diabetes Care 1983; 6:483.
- Hoffmann J, Spengler M. Efficacy of 24-week monotherapy with acarbose, glibenclamide, or placebo in NIDDM patients. The Essen Study. Diabetes Care 1994; 17:561.
- Chiasson JL, Josse RG, Hunt JA, et al. The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial. Ann Intern Med 1994; 121:928.
- Holman RR, Cull CA, Turner RC. A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44). Diabetes Care 1999; 22:960.
- Mitrakou A, Tountas N, Raptis AE, et al. Long-term effectiveness of a new alpha-glucosidase inhibitor (BAY m1099-miglitol) in insulin-treated type 2 diabetes mellitus. Diabet Med 1998; 15:657.
- Johnston PS, Coniff RF, Hoogwerf BJ, et al. Effects of the carbohydrase inhibitor miglitol in sulfonylurea-treated NIDDM patients. Diabetes Care 1994; 17:20.
- Johnston PS, Lebovitz HE, Coniff RF, et al. Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients. J Clin Endocrinol Metab 1998; 83:1515.
- Johnston PS, Feig PU, Coniff RF, et al. Long-term titrated-dose alpha-glucosidase inhibition in non-insulin-requiring Hispanic NIDDM patients. Diabetes Care 1998; 21:409.
- Johnston PS, Feig PU, Coniff RF, et al. Chronic treatment of African-American type 2 diabetic patients with alpha-glucosidase inhibition. Diabetes Care 1998; 21:416.
- Chiasson JL, Naditch L, Miglitol Canadian University Investigator Group. The synergistic effect of miglitol plus metformin combination therapy in the treatment of type 2 diabetes. Diabetes Care 2001; 24:989.
- van de Laar FA, Lucassen PL, Akkermans RP, et al. Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis. Diabetes Care 2005; 28:154.
- Hoffmann J, Spengler M. Efficacy of 24-week monotherapy with acarbose, metformin, or placebo in dietary-treated NIDDM patients: the Essen-II Study. Am J Med 1997; 103:483.
- Chiasson JL, Josse RG, Gomis R, et al. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA 2003; 290:486.
- Catalan VS, Couture JA, LeLorier J. Predictors of persistence of use of the novel antidiabetic agent acarbose. Arch Intern Med 2001; 161:1106.
- Andrade RJ, Lucena MI, Rodríguez-Mendizábal M. Hepatic injury caused by acarbose. Ann Intern Med 1996; 124:931.
- Carrascosa M, Pascual F, Aresti S. Acarbose-induced acute severe hepatotoxicity. Lancet 1997; 349:698.
- Fujimoto Y, Ohhira M, Miyokawa N, et al. Acarbose-induced hepatic injury. Lancet 1998; 351:340.
- Sjöström L, Rissanen A, Andersen T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet 1998; 352:167.
- Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA 1999; 281:235.
- Heymsfield SB, Segal KR, Hauptman J, et al. Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med 2000; 160:1321.
- Hollander PA, Elbein SC, Hirsch IB, 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.
- Miles JM, Leiter L, Hollander P, et al. Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin. Diabetes Care 2002; 25:1123.
- Kelley DE, Bray GA, Pi-Sunyer FX, et al. Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: A 1-year randomized controlled trial. Diabetes Care 2002; 25:1033.