Parthan Girish, Bhansali Shobhit, Kurpad Anura V, Walia Rama, Bhat Kishor, Bhansali Anil
Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Sector- 12, Chandigarh, PIN Code-160012, India.
Department of Physiology, St. John's Medical College, Bangalore, India.
BMC Pharmacol Toxicol. 2018 Jul 3;19(1):38. doi: 10.1186/s40360-018-0228-z.
Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control by promoting GLP1-mediated glucose-dependent insulin secretion and suppression of glucagon. Sitagliptin and vildagliptin have been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, these patients had uncontrolled blood glucose at inclusion; therefore, the improvement in insulin sensitivity observed in these studies could be attributed to the drug per se and/or reduction in glucotoxicity. This study examines the effect of linagliptin on insulin sensitivity and β-cell function in patients with well-controlled T2DM.
Thirty patients with T2DM of duration ≤5 years, and having HbA1c < 7.5% were randomized to receive linagliptin, voglibose or placebo (n = 10 each), and were followed up for 6 months. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and insulin secretory response was measured by basal (M) and postprandial (M) β-cell function, and area under curve (AUC) for C-peptide during mixed meal tolerance test.
The median HbA1c of the study subjects at inclusion was 6.9% and there was no significant difference among the groups in terms of age, duration of diabetes, body mass index (BMI), HbA1c, insulin sensitivity, AUC of C-peptide and M and M at baseline. At the end of the study, there was a modest reduction in HbA1c (- 0.2%) in the linagliptin group, and a significant decrease (- 0.8%) in the voglibose group, as compared to placebo (p = 0.038). However, there were no significant differences in insulin sensitivity, M and M and AUC of C-peptide, within, or among the groups.
Linagliptin modestly improves glycemic profile in patients with well controlled T2DM; however, it may not have an effect on insulin sensitivity in these patients.
Retrospectively Registered in Clinicaltrials.gov (ID number, NCT02097342 ). Registered: March 27, 2014.
二肽基肽酶4（DPP4）抑制剂通过促进胰高血糖素样肽1（GLP1）介导的葡萄糖依赖性胰岛素分泌和抑制胰高血糖素，改善血糖控制。西他列汀和维格列汀已被证明可改善2型糖尿病（T2DM）患者的胰岛素敏感性。然而，这些患者在纳入研究时血糖未得到控制；因此，在这些研究中观察到的胰岛素敏感性改善可能归因于药物本身和/或糖毒性的降低。本研究探讨利格列汀对血糖控制良好的T2DM患者胰岛素敏感性和β细胞功能的影响。
30例病程≤5年、糖化血红蛋白（HbA1c）<7.5%的T2DM患者被随机分为接受利格列汀、伏格列波糖或安慰剂组（每组n = 10），并随访6个月。通过高胰岛素-正常血糖钳夹评估胰岛素敏感性，通过基础（M）和餐后（M）β细胞功能以及混合餐耐量试验期间C肽曲线下面积（AUC）测量胰岛素分泌反应。
纳入研究时，研究对象的HbA1c中位数为6.9%，各组在年龄、糖尿病病程、体重指数（BMI）、HbA1c、胰岛素敏感性、C肽AUC以及基线时的M和M方面无显著差异。在研究结束时，与安慰剂相比，利格列汀组的HbA1c有适度降低（-0.2%），伏格列波糖组有显著降低（-0.8%）（p = 0.038）。然而，各组内或组间在胰岛素敏感性、M和M以及C肽AUC方面无显著差异。
利格列汀可适度改善血糖控制良好的T2DM患者的血糖状况；然而，它可能对这些患者的胰岛素敏感性没有影响。
在Clinicaltrials.gov上进行回顾性注册（注册号，NCT02097342）。注册日期：2014年3月27日。
