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 beta-cell 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 A(1c) (HbA(1c)) were stratified according to baseline IR stage (homeostasis model assessment [Homa IR] <5, ≥5), body mass index (BMI) (<27, ≥27 to <30, ≥30 kg/m(2)), 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, HbA(1c), BMI, Homa IR, duration of T2DM and metformin use of 58 years, 7.7%, 32 kg/m(2), 4.3, 5.9 years and 3.0 years, respectively. Reductions from baseline in HbA(1c) with vildagliptin were very similar across Homa IR (mean 2.8 and 8.6), BMI (mean 24.9, 28.5, and 35.3 kg/m(2)), T2DM duration (mean 0.6, 2.9, and 9.7 years), and duration of metformin use (mean 0.6, 2.6, and 7.9 years) categories, showing significant drops in HbA(1c) 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 long-standing T2DM can benefit from treatment with the DPP-4 inhibitor, vildagliptin.