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.

OBJECTIVERecent experimental studies have shown that dipeptidyl peptidase 4 (DPP-4) inhibitors have antiatherosclerotic benefits in glucagon-like peptide 1-dependent and -independent manners. The current study investigated the effects of alogliptin, a DPP-4 inhibitor, on the progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODSThis prospective, randomized, open-label, blinded-end point, multicenter, parallelgroup, comparative study included 341 patients with T2DM free of a history of apparent cardiovascular diseases recruited at 11 clinical units and randomly allocated to treatment with alogliptin (n = 172) or conventional treatment (n = 169). Primary outcomes were changes in mean common and maximum intima-media thickness (IMT) of the carotid artery measured by carotid arterial echography during a 24-month treatment period. RESULTSAlogliptin treatment had a more potent glucose-lowering effect than the conventional treatment (20.3 6 0.7% vs. 20.1 6 0.8%, P = 0.004) without an increase of hypoglycemia. Changes in the mean common and the right and left maximum IMT of the carotid arteries were significantly greater after alogliptin treatment than after conventional treatment (20.026 mm [SE 0.009] CONCLUSIONSAlogliptin treatment attenuated the progression of carotid IMT in patients with T2DM free of apparent cardiovascular disease compared with the conventional treatment.

The aim of the present study was to investigate the prevalence of fear of hypoglycemia, in association with severe hypoglycemia and social factors, in insulin-treated patients with type 2 diabetes mellitus. A questionnaire survey on hypoglycemia and patient–physician communication was carried out in 355 patients with insulin-treated type 2 diabetes mellitus patients at 16 hospitals and clinics. A fear of hypoglycemia was reported by 27.7% of patients. A stepwise logistic regression analysis found that severe hypoglycemia during the past 1 year was a significant determinant of fear of hypoglycemia (odds ratio 2.16, 95% confidence interval 1.06–4.41; P = 0.034), and age (odds ratio 1.02, 95% confidence interval 1.00–1.05, P = 0.038) and living alone (odds ratio 1.93, 95% confidence interval 1.00–3.73, P < 0.05) were significantly higher in patients with fear of hypoglycemia than in those without it.

Background: This study aimed to investigate the preventive effects of tofogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD) by monitoring carotid intima-media thickness (IMT). Methods: This prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study included 340 subjects with T2DM and no history of apparent CVD recruited at 24 clinical units. Subjects were randomly allocated to either the tofogliflozin treatment group (n = 169) or conventional treatment group using drugs other than SGLT2 inhibitors (n = 171). Primary outcomes were changes in mean and maximum common carotid IMT measured by echography during a 104-week treatment period. Results: In a mixed-effects model for repeated measures, the mean IMT of the common carotid artery (mean-IMT-CCA), along with the right and left maximum IMT of the CCA (max-IMT-CCA), significantly declined in both the tofogliflozin (− 0.132 mm, SE 0.007; − 0.163 mm, SE 0.013; − 0.170 mm, SE 0.020, respectively) and the control group (− 0.140 mm, SE 0.006; − 0.190 mm, SE 0.012; − 0.190 mm, SE 0.020, respectively). Furthermore, the tofogliflozin and the conventional treatment group did not significantly differ in the progression of the mean-IMT-CCA (mean change (95% CI) 0.008 (− 0.009, 0.025) mm, P = 0.34), along with the right (mean change (95% CI) 0.027 (− 0.005, 0.059) mm, P = 0.10) and the left max-IMT-CCA (mean change (95% CI) 0.020 (− 0.030, 0.070), P = 0.43). Similar findings were obtained even after adjusting for traditional CV risk factors and/or administration of drugs at baseline. Relative to the control treatment effects, tofogliflozin significantly reduced the HbA1c, blood glucose level, body weight/body mass index, abdominal circumference, and systolic blood pressure, and significantly increased the HDL-C. The total and serious adverse events incidences did not significantly vary between the treatment groups.

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