Dipeptidyl Peptidase-4 Inhibition in Patients with Type 2 Diabetes Treated with Saxagliptin, Sitagliptin, or Vildagliptin

Abstract

IntroductionSaxagliptin, sitagliptin, and vildagliptin are dipeptidyl peptidase-4 (DPP-4) inhibitors widely approved for use in patients with type 2 diabetes. Using a crossover design, the present study compared trough levels of DPP-4 inhibition provided by these agents in a single cohort of patients with type 2 diabetes.MethodsThis was a randomized, placebo-controlled, open-label, five-period crossover study. Eligible patients were 18–65 years of age, either treatment-naïve or off prior antihyperglycemic agent therapy for at least 6 or 12 weeks (depending on the prior therapy), and had glycated hemoglobin (HbA1C) ≥6.5% and ≤10.0%. In separate study periods, patients received 5 mg saxagliptin q.d. (saxa-5), 100 mg sitagliptin q.d. (sita-100), 50 mg vildagliptin q.d. (vilda-50-q.d.), 50 mg vildagliptin b.i.d. (vilda-50-b.i.d.), or placebo for 5 days. The primary endpoint was trough %DPP-4 inhibition, derived by comparing DPP-4 activity 24 h after the Day-5 morning dose with predose activity in the same period and analyzed using a linear mixed-effects model with fixed-effects terms for treatment and period.ResultsMean (range) baseline HbA1C was 7.4% (6.4–9.0%; N = 22). Least-squares (LS) mean trough %DPP-4 inhibition was 73.5%, 91.7%, 28.9%, 90.6%, and 3.5% after saxa-5, sita-100, vilda-50-q.d., vilda-50-b.i.d., and placebo, respectively. In patients treated with sita-100, the LS-mean difference in trough %DPP-4 inhibition was 18.2% greater than with saxa-5 (p < 0.001), 62.9% greater than with vilda-50-q.d. (p < 0.001), 1.1% greater than with vilda-50-b.i.d. (p = 0.128), and 87.8% greater than with placebo (p < 0.001). Mean %DPP-4 inhibition was nearly maximal at 12 h postdose regardless of active treatment. Thus, these between-group comparisons at trough primarily reflected differences in duration of action. Adverse events reported during the study were transient and mild or moderate in intensity.ConclusionOnce daily treatment with sitagliptin provided trough DPP-4 inhibition significantly greater than saxagliptin or vildagliptin administered once daily, and similar to that provided by vildagliptin administered twice daily.

Efficacy and safety of teneligliptin

“…[34] Whether that translates into any lower glycemic efficacy with teneligliptin compared to other DPP-4Is is yet to be seen, as no head-to-head trial is being currently done or undergoing.…”

Effects of 50 mg vildagliptin twice daily <i>vs.</i> 50 mg sitagliptin once daily on blood glucose fluctuations evaluated by long-term self-monitoring of blood glucose

“…Hypoglycemia was defined as blood glucose levels less than 70 mg/dL. All patients were encouraged to differ in structure, metabolism, potency and half-life [10], differences in clinical outcomes have not yet been fully elucidated. Therefore, we compared differences in glucose fluctuation for two DPP-4 inhibitors, sitagliptin and vildagliptin, in long-term ambulatory care using self-monitoring of blood glucose (SMBG).…”

Dipeptidyl peptidase-4 inhibitors

“…Nevertheless, DPP-4 activity is inhibited for longer than would be predicted because the inhibitors remain bound to the enzyme until slow hydrolysis breaks the covalent bonds, meaning that saxagliptin can be used once daily and vildagliptin twice daily. Accordingly, despite the differences in half-life, direct comparison reveals that the extent of DPP-4 inhibition obtained with sitagliptin and vildagliptin is comparable (and greater than that achieved with saxagliptin) when the inhibitors are used at their therapeutic doses (once daily for saxagliptin and sitagliptin, twice daily for vildagliptin) [2].…”