Impact of insulin resistance, body mass index, disease duration, and duration of metformin use on the efficacy of vildagliptin

Abstract

Introduction: The optimal stage for dipeptidyl peptidase-4 (DPP-4) inhibitor therapy in the course of type 2 diabetes mellitus (T2DM) is still under discussion, with often a perception that treatment with these agents may be less beneficial with increasing disease progression, due to loss of beta-cell function, and with increasing insulin resistance (IR), where betacell function is less prominent. This work, therefore, aimed to assess the impact of such factors on the efficacy of the DPP-4 inhibitor, vildagliptin, in add-on therapy to metformin. Methods: A pooled analysis of 24-week efficacy data of vildagliptin 50 mg twice daily (b.i.d.) (n = 2,478) from four add-on to metformin studies was performed. Analyses for changes in hemoglobin A1c (HbA1c) were stratified according to baseline IR stage (homeostasis model assessment [Homa IR]<5, ≥5), body mass index (BMI) (<27, ≥27 to<30, ≥30 kg/m2), T2DM duration (0 to<1, ≥1 to<5, ≥5 years), and duration of metformin use (0 to<1, ≥1 to <5, ≥5 years). Data from patients treated with sulfonylureas (SUs) (n = 2,010) in the pooled studies are provided as reference. Results: Patients in the vildagliptin and SU groups had mean age, HbA1c, BMI, Homa IR, durationofT2DMand metformin use of 58 years, 7.7%, 32 kg/m2, 4.3, 5.9 years and 3.0 years, respectively. Reductions from baseline in HbA1c with vildagliptin were very similar across Homa IR (mean 2.8 and 8.6), BMI (mean 24.9, 28.5, and 35.3 kg/m2), T2DMduration (mean 0.6, 2.9, and 9.7 years), and durationofmetforminuse (mean 0.6, 2.6, and 7.9 years) categories, showing significant drops in HbA1c of approximately -0.7% (baseline 7.7%). The results in patients receiving SUs were comparable to those seen in the vildagliptin group. Conclusion: Vildagliptin add-on therapy to metformin was efficacious independent of IR stage and BMI, as well as disease duration and duration of prior metformin use, indicating that, contrary to a not uncommon perception, more obese patients and patients with longstanding T2DM can benefit from treatment with the DPP-4 inhibitor, vildagliptin. © The Author(s) 2012.