Effect of Teneligliptin versus Glimepiride on Tumour Necrosis Factor Alpha and High Sensitivity C-Reactive Protein in Type 2 Diabetes Mellitus Patients Treated with Metformin: A Randomised Double-blind Parallel Group Study

Abstract

Introduction: Inflammatory markers like Tumour Necrosis Factor-α (TNF-α), C-Reactive Protein (CRP), and Interleukin-6 (IL-6) play intermediary role in insulin resistance, pathogenesis of Type 2 Diabetes Mellitus (T2DM) and its complications. Hence, antidiabetic drugs having anti-inflammatory effects may play an important role in management of T2DM and prevention of its complications. Aim: To study the effect of glimepiride versus teneligliptin on TNF-α, high sensitivity C-reactive Protein (hsCRP) and Diabetic Peripheral Neuropathy (DPN) in T2DM patients on metformin. Materials and Methods: The randomised, double-blind, parallel group study was conducted in Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India, from April 2018 to October 2019. Total 44 participants were screened and 40 participants of either gender, age range of 35-65 years, Body Mass Index (BMI) ≥25-≤35 kg/m2 and Fasting Blood Sugar ≥126 to ≤200 mg/dL, and glycosylated-haemoglobin (HbA1c) 7.0 to ≤10.0% were included into the study. The T2DM patients (N=40) on metformin (1500- 2500 mg/day) were randomised to receive glimepiride (2 mg/day) and teneligliptin (20 mg/day) in group A and group B for 12 weeks, respectively. TNF-α, hsCRP and Vibration-Perception Threshold (VPT) at baseline, 4 weeks and 12 weeks were evaluated for all participants. FBS, HbA1c, Adverse Drug Reactions (ADRs) were also recorded. Unpaired t-test and repeated-measures Analysis of Variance (ANOVA) for normally-distributed variables using Shapiro-Wilk’s test was done. Mann-Whitney and Friedman’s test for non normally distributed variables; for between-group and within-group analysis, respectively were done. Results: Forty T2DM patients (17 males and 23 females) with mean age of 49.45±6.8 and 50.3±7.9 years, were studied. The mean TNF-α level reduced significantly, in group B (159.25±58.58 to 83.15±26.18 pg/mL; p-value<0.001) from baseline to 12 weeks. Similar significant reduction was seen in the group A (175.2±66.13 to 116.15±63.32 pg/mL; p-value<0.05). There was significant reduction observed in mean VPT-scores (25±6 to 18.0±5.22 V; p-value<0.001) and (26±12.11 to 25±12 V; p-value<0.05) in group B and group A, at 12 weeks, respectively. However, both study groups showed non significant decrease in mean hsCRP levels at 12 weeks. There was a non significant reduction in all study parameters at four weeks. Mean percentage reduction of 34% and 44% in TNF-α, 13% and 11% in hsCRP and 7% and 27% in VPT-scores was observed in group A and group B, respectively at 12 weeks. Improvement in FBS and HbA1c levels (p-value<0.001) was observed in both study groups. Both treatments were tolerated well and no serious adverse drug reactions were observed. Conclusion: Teneligliptin by reducing TNF-α level, demonstrated modest anti-inflammatory activity along with metformin, by 12 weeks. It also improved VPT-scores. Glimepiride showed lesser degree of anti-inflammatory activity compared to teneligliptin. Both study drugs did not affect hsCRP levels.