ArticlesVoglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese individuals with impaired glucose tolerance
Introduction
Metabolic disorders with a predisposition towards impaired glucose intolerance and ultimately type 2 diabetes mellitus are a major health problem.1, 2 In 2002, the Japanese Ministry of Health, Labour and Welfare estimated that 7·4 million patients in Japan had diabetes and, more worryingly, 8·8 million people were considered to be possibly diabetic on the basis of HbA1c levels that were between 5·6% and 6·1%. The number of individuals with diabetes had increased by almost 2 million since the 1997 survey.3
Although type 2 diabetes has a genetic basis, evidence supports a key part played by modifiable behavioural risk factors such as obesity and physical inactivity.4 Disorders such as impaired glucose intolerance and metabolic syndrome seem to be intermediate stages between normal glucose tolerance and overt diabetes, and greatly increase the risk of type 2 diabetes and its attendant macroangiopathy.5, 6, 7 The International Diabetes Federation Taskforce on Prevention and Epidemiology convened a consensus workshop in Lisbon, Portugal, and recommended a three-step approach—identification of those at risk, measurement of the risk, and appropriate intervention—to prevent or delay the development of type 2 diabetes.8 At the core of this strategy is lifestyle modification—ie, dietary control and increased exercise, but the International Diabetes Federation recognises that pharmacotherapy might be needed in some individuals who cannot maintain such behavioural changes.
The European DECODE study,5, 9 a meta-analysis of 13 prospective cohort studies, some in Asian individuals,10 reported that impaired glucose tolerance is a prognostic factor for both all-cause and cardiovascular death. Thus, impaired glucose tolerance not only increases the likelihood of developing diabetes, but also exacerbates macrovascular pathological changes. Treatment strategies designed to slow or delay the progression of impaired glucose tolerance therefore have the potential to reduce cardiovascular morbidity and mortality, and some of the burden on health-care resources. Indeed, results of large, well designed trials have suggested that intensive diet and exercise programmes,11, 12, 13 and pharmacological intervention,13, 14, 15, 16, 17, 18, 19, 20 help prevent or delay the development of diabetes in high-risk individuals with impaired glucose tolerance.
Diabetes is a global problem, and its prevalence in Asia is predicted to increase substantially over the next 25 years. Studies specifically involving Asian people include the Da Qing study in China,11 the Indian Diabetes Prevention Programme,21 and a Japanese lifestyle intervention trial.22 Until now, no active drug intervention trial in Japanese individuals with impaired glucose tolerance has been reported. We therefore investigated the effectiveness of voglibose, an α-glucosidase inhibitor that reduces diurnal insulin secretion,23, 24, 25 for prevention of the development of type 2 diabetes in Japanese patients with impaired glucose tolerance.
Section snippets
Study design
This study was a multicentre, randomised, double-blind, parallel group comparison of voglibose and placebo in Japanese individuals with impaired glucose tolerance. From April, 2003, we aimed to treat people until type 2 diabetes or normoglycaemia was diagnosed, or for at least 3 years. The Independent Data Monitoring Committee planned an interim analysis to investigate whether or not to continue the study on the basis of efficacy and safety findings.
Procedure
We recruited individuals from 103 Japanese
Results
The Independent Data Monitoring Committee did an interim analysis in March, 2007, with data from 1778 individuals that had been gathered by October, 2006. The cumulative number of cases of type 2 diabetes in the interim analysis was 84 in the placebo group and 40 in the voglibose group. The HR was 0·577 (two-sided 95% CI 0·404–0·825; p=0·0026), verifying the efficacy of voglibose compared with placebo and, accordingly, the Independent Data Monitoring Committee made the decision to terminate the
Discussion
In our trial, even though we reinforced diet and exercise programmes, individuals remained at risk of developing diabetes. Voglibose significantly reduced the risk of individuals with impaired glucose tolerance developing type 2 diabetes and significantly increased the proportion of people who achieved normoglycaemia compared with placebo. Because of the high normalisation rate and the early termination of the trial, the average duration of treatment was about 1 year. Thus, the clinically
References (31)
- et al.
The metabolic syndrome
Lancet
(2005) - et al.
Acarbose for prevention of type 2 diabetes mellitus : the STOP-NIDDM randomised trial
Lancet
(2002) - et al.
Prevention of type 2 diabetes by lifestyle intervention: a Japanese trial in IGT males
Diabetes Res Clin Pract
(2005) - et al.
Combination therapy of alpha-glucosidase inhibitor and a sulfonylurea compound prolongs the duration of good glycemic control
Metabolism
(2002) - et al.
Effect of two α-glucosidase inhibitors, voglibose and acarbose, on postprandial hyperglycemia correlates with subjective abdominal symptoms
Metabolism Clin Exp
(2005) - et al.
The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study
Lancet
(2008) Diabetes in America: epidemiology and scope of the problem
Diabetes Care
(1998)Diabetes facts and figures
2002 diabetes mellitus survey report
(2004)Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”?
Am J Hum Genet
(1962)
Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria
Lancet
The clinical implications of impaired glucose tolerance
Diabet Med
International Diabetes Federation: a consensus on type 2 diabetes prevention
Diabet Med
Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria
Arch Intern Med
Hyperglycaemia and mortality from all causes and from cardiovascular disease in five populations of Asian origin
Diabetologia
Cited by (258)
Synthesis, in vitro α-glucosidase activity and in silico molecular docking study of isatin analogues
2023, Chemical Data CollectionsRole of newer anti-diabetes drugs in prediabetes: A systematic review
2023, Metabolic Syndrome: From Mechanisms to InterventionsManagement of type 2 diabetes without insulin: An update for the PCP
2022, Disease-a-MonthUnravelling the involvement of gut microbiota in type 2 diabetes mellitus
2021, Life SciencesCitation Excerpt :Other drugs that can be administered to diabetic patients include alpha glucosidase inhibitors such as voglibose, acarbose are safer drugs but are not in much use as well as have adverse effects including bloating and diarrhea [59]. Voglibose belonging to this category can increase toleration to glucose [69]. There are various incretin associated treatments such as congeners of glucagon like peptide 1 (e.g.: exenatide) that cause improved blood glucose levels as well as manages body weight; apart from this, improve cardiac as well as liver health and improve inflammation [70].
Recurrent reactive hypoglycemia due to clozapine-induced glucose intolerance: A case report
2023, Psychiatry and Clinical Neurosciences Reports
- ‡
A full list of investigators and research institutions is provided at the end of the paper