Voglibose for Prevention of Type 2 Diabetes Mellitus - Voglibose for Prevention of Type 2 Diabetes Mellitus

Aug 10, 2009
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Trial Sponsor:
Takeda Pharmaceuticals
Date Published:
01/01/2009
Date Updated:
08/10/2009
Original Posted Date:
08/10/2009
References

Description:

Impaired fasting glucose has been shown to be associated with adverse clinical outcomes, including mortality. This trial sought to compare the effectiveness of voglibose with placebo in the prevention of the development of type 2 diabetes mellitus (T2DM) in patients with impaired fasting glucose.

Hypothesis:

Voglibose would be superior to placebo in the prevention of the development of T2DM in patients with impaired fasting glucose.

Study Design

Study Design:

Patients Screened: 4,582
Patients Enrolled: 1,780
Mean Follow Up: Mean duration: 48.1 weeks
Mean Patient Age: 55.7 years
Female: 40

Patient Populations:

  • Fasting plasma glucose <126 mg/dl
  • 2-hour plasma glucose concentration during oral glucose tolerance test between 140 and 198 mg/dl
  • Glycated hemoglobin <6.5%
  • At least one risk factor for diabetes: high normal blood pressure (≥130/80 mm Hg), treatment for hypertension, dyslipidemia, body mass index >25 kg/m2, family history of diabetes

Exclusions:

  • Diabetes mellitus
  • Disease that is likely to impair glucose tolerance

Primary Endpoints:

  • Development of T2DM

Secondary Endpoints:

  • Number of people who achieve normoglycemia

Drug/Procedures Used:

Four weeks after randomization, patients were randomized to receive either 0.2 mg three times daily of voglibose or matching placebo.

Concomitant Medications:

Angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker 32.5%. Four to eight weeks before the start of treatment, each person was given advice about appropriate nutrition and exercise programs.

Principal Findings:

A total of 1,780 patients were randomized, 897 to voglibose, and 881 to placebo. Baseline characteristics were fairly similar between the two arms. Baseline fingerstick blood glucose was around 104 mg/dl. About 59% of the patients had coexisting hypertension, 77% had dyslipidemia, 57% were obese, and 38% had a family history of diabetes. About 62% had three or more risk factors for the development of diabetes.

The trial was terminated early, when an interim analysis demonstrated a significant reduction in the incidence of diabetes with voglibose compared with placebo (5.6% vs. 12.0%, hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.43-0.82, p = 0.0014), over a mean duration of 48.1 weeks of treatment. After 144 weeks of follow-up, the cumulative rate of progression to T2DM was still lower in the voglibose arm (8.0% vs. 17.2%, p < 0.0001). Benefit seemed to be pronounced in patients with three or more risk factors (HR 0.61, 95% CI 0.43-0.86, p = 0.005). Improvement to normoglycemia was also higher in the voglibose arm (66.8% vs. 51.5%, HR 1.54, 95% CI 1.36-1.75, p < 0.0001).

Adverse effects were more frequent in the voglibose arm, including gastrointestinal side effects such as diarrhea (13% vs. 5%), flatulence (17% vs. 7%), abdominal distension (13% vs. 5%), and dizziness (1% vs. <1%). Laboratory values such as creatine kinase and liver-associated enzymes were similar between the two arms.

Interpretation:

The results of this trial indicate that voglibose, in addition to diet and lifestyle modification, is associated with a significant reduction in the incidence of T2DM, and a greater incidence of normoglycemia attainment in Japanese patients at risk for developing T2DM, compared with placebo. Since this trial was terminated early, the mean follow-up was about 1 year. However, the benefit seemed to be sustained for up to 3 years in patients in whom longer follow-up was available.

Voglibose is an alpha-glucosidase inhibitor, similar to acarbose, and reduces diurnal insulin secretion. The STOP-NIDDM trial had noted a similar benefit with acarbose. Similarly, metformin (US-DPP) and pioglitazone (DREAM) have been shown to reduce the incidence of T2DM in patients with impaired fasting glucose.

Current recommendations for patients with impaired fasting glucose are to try diet and lifestyle modification to the fullest extent possible, failing which one of the above medications can be considered. Voglibose seems like a reasonable alternative in such a scenario.

References:

Kawamori R, Tajima N, Iwamoto Y, Kashiwagi A, Shimamoto K, Kaku K, on behalf of the Voglibose Ph-3 Study Group. Voglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese individuals with impaired glucose tolerance. Lancet 2009;373:1607-14.

Keywords: Life Style, Follow-Up Studies, Creatine Kinase, Inositol, Diabetes Mellitus, Type 2, Diarrhea, Risk Factors, Insulins, Glycated Hemoglobin A, Dyslipidemias, Body Mass Index, Dizziness, Glucose Tolerance Test, Blood Glucose, Metformin, Liver, Hypoglycemic Agents, Confidence Intervals, Acarbose, Flatulence, Hypertension, Thiazolidinediones, Fasting


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