Background: In order to test the hypothesis that the degree of weight change with the dipeptidyl peptidase-4 inhibitor vildagliptin is dependent on the level of glycemic control at baseline, the weight changes from pooled monotherapy studies after 24 weeks of therapy with vildagliptin were assessed versus the fasting plasma glucose (FPG) levels at baseline.
Methods: Data were pooled from eight clinical monotherapy trials including 2,340 previously drug-naïve patients with type 2 diabetes mellitus who received vildagliptin monotherapy (50 mg once daily [n=359] or 50 mg twice daily [n=1,981]). The trials were all randomized, double-blind, controlled clinical trials with a prespecified week 24 study visit.
Results: Linear regression analysis of weight change after 24 weeks relative to baseline FPG showed an intercept of -2.259 kg (95% confidence interval -2.86, -1.66; P<0.0001) and a positive slope of 0.1552 kg (95% confidence interval 0.10-0.21; P<0.0001). Neutral caloric balance (no weight change) was observed at a FPG of 14.6 mmol/L (263 mg/dL). Baseline FPG values below and above this threshold were associated with weight loss and weight gain, respectively. For instance, from this analysis, a baseline FPG of 8 mmol/L (144 mg/dL) predicts a weight loss of 1 kg.
Conclusion: The present analysis showed that treatment with vildagliptin results in a negative caloric balance when glucose levels are below the renal threshold at baseline.
Keywords: dipeptidyl peptidase-4 inhibitor; glucagon-like peptide-1; hyperglycemia; renal threshold; sodium-glucose cotransporter-2 inhibitor.