Abstract
IntroductionSodium-glucose co-transporter-2 (SGLT2) inhibitors are anti-diabetic agents that improve glycemic control with a low risk of hypoglycemia and ameliorate a variety of cardiovascular risk factors. The aim of the ongoing study described herein is to investigate the preventive effects of tofogliflozin, a potent and selective SGLT2 inhibitor, on the progression of atherosclerosis in subjects with type 2 diabetes (T2DM) using carotid intima-media thickness (IMT), an established marker of cardiovascular disease (CVD), as a marker.MethodsThe Study of Using Tofogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, blinded-endpoint, multicenter, and parallel-group comparative study. The aim was to recruit a total of 340 subjects with T2DM but no history of apparent CVD at 24 clinical sites and randomly allocate these to a tofogliflozin treatment group or a conventional treatment group using drugs other than SGLT2 inhibitors. As primary outcomes, changes in mean and maximum IMT of the common carotid artery during a 104-week treatment period will be measured by carotid echography. Secondary outcomes include changes in glycemic control, parameters related to β-cell function and diabetic nephropathy, the occurrence of CVD and adverse events, and biochemical measurements reflecting vascular function.ConclusionThis is the first study to address the effects of SGLT2 inhibitors on the progression of carotid IMT in subjects with T2DM without a history of CVD. The results will be available in the very near future, and these findings are expected to provide clinical data that will be helpful in the prevention of diabetic atherosclerosis and subsequent CVD.FundingKowa Co., Ltd.Clinical Trial RegistrationUMIN000017607.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0292-1) contains supplementary material, which is available to authorized users.
Highlights
Sodium-glucose co-transporter-2 (SGLT2) inhibitors are anti-diabetic agents that improve glycemic control with a low risk of hypoglycemia and ameliorate a variety of cardiovascular risk factors
Several studies have shown that abnormal glycemic metabolism plays an important role in the pathogenesis of atherosclerosis and that poor glycemic control accelerates the risk for cardiovascular disease (CVD) in subjects with type 2 diabetes mellitus (T2DM) [3]
Since the mode of action of SGLT2 inhibitors is independent of insulin secretion, these agents are associated with a low risk of hypoglycemia, which is linked to an increased of CV events [7, 8, 16]
Summary
Atherosclerotic cardiovascular disease (CVD), which is accelerated in patients with prolonged diabetes, impairs quality of life and is a major cause of mortality [1, 2]. Since the mode of action of SGLT2 inhibitors is independent of insulin secretion, these agents are associated with a low risk of hypoglycemia, which is linked to an increased of CV events [7, 8, 16] They have been demonstrated to ameliorate a variety of CV risk factors and potential pathways: these agents, as monotherapy or in combination with other glucose-lowering drugs, reduce visceral adipose tissue, body weight, blood pressure, and circulating uric acid levels as well as improve serum lipid profiles [17]. These findings indicate a strong rationale for expecting that these compounds will protect against CV events. An assessment will be performed by chronologically observing the preventive effects of tofogliflozin on the progression of intima-media thickness (IMT) of the carotid artery, a surrogate endpoint of atherosclerosis [24, 25]
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