Rationale, design, and baseline characteristics of a clinical trial for prevention of atherosclerosis in patients with insulin-treated type 2 diabetes mellitus using DPP-4 inhibitor: the Sitagliptin Preventive study of Intima-media thickness Evaluation (SPIKE).

Tomoya Mita,Naoto Katakami,Hidenori Yoshii,Toshihiko Shiraiwa,Kazunari Matsumoto,Mamiko Tsugawa,Hiroki Yokoyama,Nobuichi Kuribayashi,Tomio Onuma,Hideaki Kaneto,Tsunehiko Yamamoto,Yutaka Umayahara,Keisuke Kosugi,Hirotaka Watada,Iichiro Shimomura,Masahiko Gosho,Takeshi Osonoi

doi:10.1186/1758-5996-6-35

Abstract

BackgroundSitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is currently used to achieve glycemic targets in patients with type 2 diabetes mellitus (T2DM). The addition of DPP-4 inhibitors to ongoing insulin therapy is expected to reduce insulin dosage, leading to a reduction in the frequency of hypoglycaemia and/or weight gain. Recent studies have demonstrated potential anti-atherosclerotic effects for DPP-4 inhibitors. The aim of the present ongoing study is to assess the effects of sitagliptin on the progression of atherosclerosis in patients with insulin-treated T2DM using carotid intima-media thickness (IMT), an established marker of cardiovascular disease.Methods and DesignThe Sitagliptin Preventive study of Intima media thickness Evaluation (SPIKE) is a prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study. Between February 2012 and September 2012, 282 participants who failed to achieve glycemic control despite insulin therapy were recruited at 12 clinics and randomly allocated to the sitagliptin group (n = 142) or the control group (n = 140). Primary outcomes are changes in maximum and mean IMT of the common carotid artery after 24-month treatment period measured by carotid arterial echography. Secondary outcomes include changes in glycemic control, parameters related to beta-cell function and diabetic nephropathy, occurrence of cardiovascular events and adverse events such as hypoglycaemia, and biochemical markers of vascular function.DiscussionThe present study is designed to assess the effects of sitagliptin on the progression of carotid IMT. Results will be available in the near future, and the findings are expected to provide new strategy to prevent atherosclerosis in patients with insulin-treated T2DM.Clinical Trial RegistrationUMIN000007396

Highlights

Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is currently used to achieve glycemic targets in patients with type 2 diabetes mellitus (T2DM)
The aim of this study is to investigate the effects of sitagliptin on the progression of atherosclerosis in insulin-treated patients with T2DM free of history of cardiovascular disease (CVD), using common carotid intima-media thickness (IMT), a widely used surrogate marker of atherosclerosis, as the primary endpoint
The Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complication (DCCT/EDIC) study indicated that intensive treatment with insulin had long-term positive effects on CVD in patients with type 1 diabetes mellitus [46]

Summary

Introduction

Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is currently used to achieve glycemic targets in patients with type 2 diabetes mellitus (T2DM). The addition of DPP-4 inhibitors to ongoing insulin therapy is expected to reduce insulin dosage, leading to a reduction in the frequency of hypoglycaemia and/or weight gain. The aim of the present ongoing study is to assess the effects of sitagliptin on the progression of atherosclerosis in patients with insulin-treated T2DM using carotid intima-media thickness (IMT), an established marker of cardiovascular disease. Patients with type 2 diabetes mellitus (T2DM) are at high risk for cardiovascular disease (CVD), which are the most frequent cause of death in these patients [1,2]. Many patients require insulin therapy in addition to OHA in order to achieve appropriate glycemic control

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