Sitagliptin Attenuates the Progression of Carotid Intima-Media Thickening in Insulin-Treated Patients With Type 2 Diabetes: The Sitagliptin Preventive Study of Intima-Media Thickness Evaluation (SPIKE)

Abstract

OBJECTIVEThe effect of additional treatment with oral hypoglycemic agents on the progression of atherosclerosis remains unknown in insulin-treated patients with type 2 diabetes mellitus (T2DM). We assessed the effects of sitagliptin, a dipeptidyl peptidase 4 inhibitor, on carotid intima-media thickness (IMT) in T2DM. RESEARCH DESIGN AND METHODSThis prospective, randomized, open-label, blinded end point, multicenter, parallelgroup, comparative study included 282 insulin-treated patients with T2DM free of a history of apparent cardiovascular diseases who were recruited at 12 clinical units and randomly allocated to either the sitagliptin group (n = 142) or the control group (n = 140). The primary outcomes were changes in mean and maximum IMT of the common carotid artery measured by echography at the end of a 104-week treatment period. RESULTSSitagliptin had a more potent glucose-lowering effect compared with the conventional treatment (20.5 6 1.0% vs. 20.2 6 0.9%; P = 0.004), without increasing hypoglycemic episodes or body weight. Changes in the mean and left maximum IMT, but not right maximum IMT, of the common carotid arteries were significantly greater after sitagliptin treatment compared with conventional treatment CONCLUSIONSSitagliptin attenuated the progression of carotid IMT in insulin-treated patients with T2DM free of apparent cardiovascular disease compared with conventional treatment.

Effects of 50 mg vildagliptin twice daily <i>vs.</i> 50 mg sitagliptin once daily on blood glucose fluctuations evaluated by long-term self-monitoring of blood glucose

“…Although some hypoglycemic agents have been used to manage glycemic fluctuation, dipeptidyl peptidase-4 (DPP-4) inhibitors are frequently prescribed because of their glucose level-dependent hypoglycemic mechanism and safety profile. These drugs not only improve HbA1c and glycemic control, but also are expected to have anti-atherosclerotic and β-cell protective effects [7][8][9]. Although DPP-4 inhibitors and 2 hours after each meal, and at bedtime) once every 1 or 2 weeks for 12 weeks.…”

Changes in carotid intima‐media thickening in patients with type 2 diabetes mellitus: Subanalysis of the Sitagliptin Preventive Study of Intima‐Media Thickness Evaluation

“…TM, NK, TS, HY, IS, MG and HW received research funds and/or have received lecture fees from several commercial sources as described in the original research1. MG received a manuscript fee from Kowa Co., Ltd.…”

“…We reported recently that treatment with sitagliptin, a dipeptidyl peptidase‐4 inhibitor, attenuated the progression of carotid IMT in insulin‐treated patients with type 2 diabetes mellitus compared with conventional therapy1. Here, we compared the efficacy of treatment with sitagliptin with that of other modalities on the progression of carotid IMT in prespecified subgroups of the Sitagliptin Preventive Study of Intima‐Media Thickness Evaluation (SPIKE) registered on the University Hospital Medical Information Network Clinical Trials Registry (UMIN000007396)1, 2. The aim of the comparison was to identify the characteristics of patients who benefited most from the sitagliptin treatment in terms of decrease in IMT.…”

“…After the exclusion of eight patients, data of 137 patients of the sitagliptin group and 137 of the conventional treatment group were subjected to analysis. The mean‐IMT of the common carotid arteries (mean‐IMT‐CCA) and right and left max‐IMT‐CCA were measured by expert sonographers at the start of the study, and the procedure was repeated after 52 and 104 weeks, as reported previously1, 2. Figure 1 shows differences in treatment‐induced delta change in carotid IMT, relative to baseline in 243 patients whose IMT data were available at baseline and 104 weeks, according to various predefined risk factors for atherosclerosis.…”

Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence

“…Recent studies have shown that aloglitpin and sitagliptin prevent the progression of carotid atherosclerosis in patients with diabetes [97,98]. Furthermore, a meta-analysis demonstrated that GLP-1-based therapy has beneficial effects on atherosclerotic markers (brain naturetic peptide, high-sensitivity C-reactive protein, plasminogen activator inhibitor-1, total cholesterol, LDL cholesterol, and triglycerides) in patients with type 2 diabetes [99].…”