Incretin-based therapies in prediabetes: Current evidence and future perspectives

Table 1 Main clinical studies of dipeptidyl peptidase-4 inhibitors in a prediabetic state

Ref.	Study population	Study design	Main results
Utzschneider et al[50]	22 individuals with IFG	VILDA was administered in a dose of 100 mg daily for 6 wk. Two weeks of placebo treatment before (running period) and after (washout period) 6 wk was studied	FPG levels were not significantly reduced. AUC GLU and 2-h GLU decreased after a MTT. DI was increased by 69% and insulin sensitivity by 25% after an IVGTT These effects were not sustained in the washout period
Rosenstock et al[51]	179 individuals with IGT (80%: IFG + IGT)	Multicenter 12-wk double-blind study 90 participants received VILDA 50 mg/daily and 89 received placebo therapy	Improvements in β-cell function as estimated by insulin secretion relative to that of GLU. Improvements were also reported in α-cell function. These beneficial effects contributed to approximately 30% reduction in prandial GLU excursions
Werzowa et al[52]	48 IGT renal transplant recipients	3-mo, double-blind, placebo-controlled study. Participants were randomized to receive 50 mg of VILDA, 30 mg of PIO or placebo in a 1:1:1 ratio (n = 16 in each arm)	A1C reduction was statistically significant between treatment groups and placebo. VILDA and PIO reduced the 2 h plasma GLU at three months compared with baseline, while only PIO reduced FPG
Bock et al[57]	22 individuals with IFG	8-wk double blind placebo-controlled study Participants received SITA 100 mg daily (n = 11) or placebo (n = 11)	SITA increased postprandial intact GLP-1 concentrations. Both fasting and postprandial GLU values were unchanged with SITA therapy. A slightly increased DI was reported
Perreault et al[58]	23 individuals with either IFG (n = 10) or NGT (n = 13)	4-wk open-label, parallel group study. All participants received SITA 100 mg once daily	SITA resulted in a small, but significant decrease in FPG compared to baseline in both groups (P < 0.05) Administration of SITA did not altered insulin or GLU excursions in the post-intervention OGTT, but did increase AUC for active GLP-1 and C-peptide compared to baseline levels (P < 0.01 for both)

GLP-1: Glucagon-like peptide 1; IFG: Impaired fasting glucose; IGT: Impaired glucose tolerance; NGT: Normal glucose tolerance; FPG: Fasting plasma glucose; AUC: Area under the curve; DI: Disposition index; IVGTT: Intravenous glucose tolerance test; MTT: Meal tolerance test; A1C: Glycated hemoglobulin; VILDA: Vildagliptin; SITA: Sitagliptin; PIO: Pioglitazone; GLU: Glucose; OGTT: Oral glucose tolerance test.