Voglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese individuals with impaired glucose tolerance

• Published in: The Lancet (British edition) Vol. 373; no. 9675; pp. 1607 - 1614
• Main Authors: Kawamori, Ryuzo, Prof, Tajima, Naoko, Prof, Iwamoto, Yasuhiko, Prof, Kashiwagi, Atsunori, Prof, Shimamoto, Kazuaki, Prof, Kaku, Kohei, Prof
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 09.05.2009; Elsevier; Elsevier Limited
• Subjects: Administration, Oral; Analysis of Variance; Biological and medical sciences; Blood pressure; Clinical medicine; Diabetes; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - etiology; Diabetes Mellitus, Type 2 - prevention & control; Diabetes. Impaired glucose tolerance; Disease Progression; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; General aspects; Glucose Intolerance - complications; Glucose Intolerance - diagnosis; Glucose Intolerance - drug therapy; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Incidence; Inositol - adverse effects; Inositol - analogs & derivatives; Inositol - therapeutic use; Internal Medicine; Japan - epidemiology; Kaplan-Meier Estimate; Life Style; Male; Medical sciences; Metabolic disorders; Metabolic syndrome; Middle Aged; Mortality; Plasma; Prevalence; Prevention and actions; Prevention programs; Proportional Hazards Models; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk Assessment; Risk factors; Risk Reduction Behavior; Severity of Illness Index; Studies; Asia; Japan; Endocrinopathy; Type 2 diabetes; Human; Enzyme; Enzyme inhibitor; Voglibose; Metabolic diseases; Japanese; Glycosylases; Medicine; Prevention; Hypoglycemic agent; Randomization; α-Glucosidase; Glycosidases; Double blind study; Hydrolases; Clinical trial; Impaired glucose tolerance
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(09)60222-1

Summary Background The increased prevalence of type 2 diabetes mellitus is a major concern for health providers. We therefore assessed whether voglibose, an α-glucosidase inhibitor, could prevent the development of type 2 diabetes in high-risk Japanese individuals with impaired glucose tolerance. Methods 1780 eligible patients on a standard diet and taking regular exercise with impaired glucose tolerance were randomly assigned to oral voglibose 0·2 mg three times a day (n=897) or placebo (n=883) in a multicentre, double-blind, parallel group trial. Treatment was continued until participants developed type 2 diabetes (primary endpoint) or normoglycaemia (secondary endpoint), or for a minimum of 3 years, subject to the findings of an interim analysis. Analysis was by full analysis set. This trial is registered with the University Hospital Medical Information Network (UMIN) clinical trials registry, number UMIN 000001109. Findings In the interim analysis, voglibose was better than placebo (p=0·0026) in individuals treated for an average of 48·1 weeks (SD 36·3). Patients treated with voglibose had a lower risk of progression to type 2 diabetes than did those on placebo (50 of 897 vs 106 of 881; hazard ratio 0·595, 95% CI 0·433–0·818; p=0·0014). More people in the voglibose group achieved normoglycaemia than did those in the placebo group (599 of 897 vs 454 of 881; 1·539, 1·357–1·746; p<0·0001). 810 (90%) of 897 patients in the voglibose group had adverse events versus 750 (85%) of 881 in the placebo group. Serious adverse events (all one each) in the voglibose group were cholecystitis, colonic polyp, rectal neoplasm, inguinal hernia, liver dysfunction, and subarachnoid haemorrhage, and in the placebo group were cerebral infarction and cholecystitis. Interpretation Voglibose, in addition to lifestyle modification, can reduce the development of type 2 diabetes in high-risk Japanese individuals with impaired glucose tolerance. Funding Takeda.