Efficacy and tolerability of vildagliptin in drug-naïve patients with type 2 diabetes and mild hyperglycaemia*.

AIM: This study was conducted to assess efficacy and tolerability of vildagliptin in drug-naïve patients with type 2 diabetes and mild hyperglycaemia. METHODS: Multicentre, double-blind, randomized, placebo-controlled, parallel-group study of 52-week treatment with vildagliptin (50 mg q.d.) in 306 drug-naïve patients with type 2 diabetes (A1C = 6.2-7.5%). A1C, fasting plasma glucose (FPG) and measures of prandial glucose control and beta-cell function determined during standard meal tests were assessed. RESULTS: Baseline A1C and FPG averaged 6.7% and 7.1 mmol/l, respectively, in patients randomized to vildagliptin (n = 156) and 6.8% and 7.2 mmol/l in those randomized to placebo (n = 150). A1C decreased modestly in vildagliptin-treated patients (Delta = -0.2 +/- 0.1%) and increased in patients receiving placebo (Delta = 0.1 +/- 0.1%). The between-group difference (vildagliptin - placebo) in adjusted mean change (AM Delta) in A1C was -0.3 +/- 0.1% (p < 0.001). FPG increased in patients receiving placebo (Delta = 0.5 +/- 0.1 mmol/l) and to a significantly lesser extent in vildagliptin-treated patients (between-group difference in AM Delta FPG = -0.4 +/- 0.2 mmol/l, p = 0.032). Relative to placebo, 2-h postprandial glucose (PPG) decreased (-0.9 +/- 0.4 mmol/l, p = 0.012), and insulin secretory rate (ISR) relative to glucose [ISR area under the curve (AUC)(0-2) (h)/glucose AUC(0-2) (h)] increased (+5.0 +/- 1.2 pmol/min/m(2)/mM, p < 0.001). Mean body weight decreased by 0.5 +/- 0.3 kg in vildagliptin-treated patients and by 0.2 +/- 0.3 kg in patients receiving placebo. The side-effect profile of vildagliptin was similar to that of placebo, and one hypoglycaemic episode occurred in one patient receiving placebo. CONCLUSIONS: In drug-naïve patients with mild hyperglycaemia, relative to placebo, 52-week treatment with vildagliptin 50 mg q.d. significantly decreases A1C, FPG and PPG and improves beta-cell function without weight gain or hypoglycaemia.

Influence of tegaserod on proximal gastric tone and on the perception of gastric distension.

BACKGROUND: Tegaserod, a 5-hydroxytryptamine-4 receptor agonist, enhances gastric emptying, but its effects on proximal stomach function have not been studied. AIM: To study the effect of tegaserod on gastric compliance, accommodation and perception of distension in humans. METHODS: Nineteen healthy volunteers (10 females; mean age, 23.9 years) were studied on three separate occasions after 7 days of treatment with placebo, tegaserod 2 mg b.d. or tegaserod 6 mg b.d. in a double-blind, randomized, three-way cross-over design. After the introduction of a barostat bag, stepwise distensions were performed to determine gastric compliance and sensitivity, and a mixed liquid meal was administered in isobaric mode to assess accommodation. RESULTS: Tegaserod had no effect on the pressures or volumes inducing first perception or discomfort. Tegaserod 6 mg b.d. enhanced fasting gastric compliance compared with placebo. Pre-prandial and post-prandial intra-balloon volumes were significantly higher after 6 mg b.d. than after placebo. Both tegaserod 2 and 6 mg b.d. shortened the time to maximum post-prandial intra-balloon volume. The amplitude of meal-induced gastric relaxation (post-prandial minus pre-prandial volumes) did not differ between the treatment arms. CONCLUSION: In humans, tegaserod allows for larger intra-balloon volumes both before and after a meal. These findings warrant the investigation of the therapeutic potential of tegaserod in dyspeptic patients with impaired accommodation.