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


CONCLUSIONS
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.
Novartis Pharma AG, Postfach, 4002, Basel, Switzerland, anja.schweizer@novartis.com.
Anja
A
Schweizer
Sylvie
S
Dejager
James E
JE
Foley