Published in:
Open Access 01-08-2011 | Article
Beta cell function following 1 year vildagliptin or placebo treatment and after 12 week washout in drug-naive patients with type 2 diabetes and mild hyperglycaemia: a randomised controlled trial
Published in: Diabetologia | Issue 8/2011
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Aims/hypothesis
Traditional blood glucose lowering agents do not prevent the progressive loss of beta cell function in patients with type 2 diabetes. The dipeptidylpeptidase (DPP)-4 inhibitor vildagliptin improves beta cell function both acutely and chronically (up to 2 years). Whether this effect persists after cessation of treatment remains unknown. Here, we assessed the insulin secretory capacity in drug-naive patients with type 2 diabetes after a 52 week treatment period with vildagliptin or placebo, and again after a 12 week washout period.
Methods
This study was conducted at a single university medical centre, and was a double-blind, randomised clinical trial in 59 drug-naive patients with type 2 diabetes and mild hyperglycaemia to either vildagliptin 100 mg (n = 29) or placebo (n = 30). Randomisation was performed by a validated 1:1 system. Neither patient, nor caregiver, was informed about the assigned treatment. Inclusion criteria were drug-naive patients ≥30 years, with HbA1c ≤7.5% and BMI of 22–45 kg/m2. The mildly hyperglycaemic patient population was chosen to minimise glucose toxicity as a confounding variable. Beta-cell function was measured during an arginine-stimulated hyperglycaemic clamp at week 0, week 52 and after a 12 week washout period. All patients with at least one post-randomisation measure were analysed (intent-to-treat).
Results
Fifty-two week vildagliptin 100 mg (n = 26) treatment increased the primary efficacy variable, combined hyperglycaemia and arginine-stimulated C-peptide secretion (AIRarg), by 5.0 ± 1.8 nmol/l × min, while it decreased by 0.8 ± 1.8 nmol/l × min with placebo (n = 25) (between-group difference p = 0.030). No significant between-group difference in AIRarg was seen after the 12 week washout period. The between-group difference adjusted mean 52 week changes from baseline was −0.19 ± 0.11, p = 0.098 and −0.22 ± 0.23%, p = 0.343 for HbA1c and fasting plasma glucose, respectively. There were no suspected drug treatment-related serious adverse events.
Conclusions/interpretation
One year treatment with vildagliptin significantly increased beta cell secretory capacity. This effect was not maintained after the washout, indicating that this increased capacity was not a disease modifying effect on beta cell mass and/or function.
Trial registration:
ClinicalTrials.gov NCT00260156
Funding:
This study was sponsored by the Novartis Pharmaceutical Cooperation.