Effects of Sitagliptin on Insulin and Glucagon Levels in Type 2 Diabetes Mellitus

Corresponding author: Ji Hyun Kim Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Paul’s Hospital, College of Medicine, The Catholic University of Korea, 180 Wangsan-ro, Dongdaemun-gu, Seoul 02559, Korea E-mail: [email protected] Recently, the use of dipeptidyl peptidase-4 (DPP4) inhibitors in the management of type 2 diabetes mellitus (T2DM) has been widespread. This class drug control the fasting and postprandial glucose (PPG) levels in a glucose dependent manner. By slowing incretin degradation, DPP4 inhibitors increase the levels of active glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, and thereby stimulate insulin secretion and suppress glucagon release based on blood glucose level [1]. Sitagliptin, a highly selective DPP4 inhibitor, also has been demonstrated to control glucose levels through the similar mode of action [2]. Since several studies have reported that DPP4 inhibitors exhibit a better glucose lowering efficacy in Asian populations than in non-Asians with T2DM [3], sitagliptin may be one of appropriate treatment for T2DM in Asian patients. Most studies showed that sitagliptin treatment leads to significant improvements in β-cell function [4]. In Asian patients, β-cell dysfunction is major pathophysiology of T2DM. Furthermore, insulin secretory defect is more prominent in Asian than in Caucasian patients [5]. The changes of plasma insulin levels and glucagon levels during oral glucose tolerance test (OGTT) could be differed by ethnic groups and could partly elucidate the response of DPP4 inhibitors. In Western patients with T2DM, there were many studies evaluating the effect of DPP4 inhibitors on blood insulin and glucagon levels. Herman et al. [1] showed that single doses of sitagliptin increased insulin (21% to 22%) and C-peptide (13% to 21%) levels, reduced plasma glucagon levels (7% to 14%), and reduced glycemic excursion following an OGTT. In shortterm clinical study of 2 weeks, sitagliptin reduced mean postprandial plasma glucagon concentration relative to baseline [6]. Relatively long-term clinical studies also evaluated markers of β-cell function such as homeostasis model of assessment of β-cell function (HOMA-β), fasting proinsulin-to-insulin ratio, fasting insulin secretion and the insulinogenic index, an index of early insulin release in response to a meal [7]. It has been reported that sitagliptin significantly improve these indices related to β-cell function in patients with T2DM [8-10]. However, clinical studies aimed to evaluate β-cell function by DPP4 inhibitor treatment in Asian patients are uncommon. In a couple of studies conducted in China, India, and Korea, sitagliptin did lead to significant improvement of indices of β-cell function, 2-hour postprandial insulin, C-peptide and the insulinogenic index [11] and saxagliptin increased HOMA-β assessment [12]. In other study, which was to evaluate the effects of sitagliptin in Japanese patients with T2DM, 3-day treatment with sitagliptin showed significant decrease of PPG and the area under the curve0 to 2 hour for glucagon throughout the meal tolerance test [13]. Moreover, it improved the insulinogenic index and suppressed glucagon responses significantly for 12 weeks [14,15]. There are few data available to assess the effect of DPP4 inhibitors on insulin or glucagon in Korean patients with T2DM. Considering already proven the stronger effect of DPP4 inhibiEditorial Others