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

Abstract

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 HbA _1c ≤7.5% and BMI of 22–45 kg/m ². 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 (AIR _arg), 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 AIR _arg 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 HbA _1c 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.