Effect of ipragliflozin on carotid intima-media thickness in patients with type 2 diabetes: a multicenter, randomized, controlled trial

Abstract

Aim To examine the effects of 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods In this multicenter, prospective, randomized, open-label, blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and hemoglobin A1C (HbA1c) of 6.0%—10.0% (42—86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up for 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. Results A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 (95% CI, -0.0155–0.0182) mm and 0.0015 (95% CI, -0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of -0.0001 mm (95% CI, -0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups (-0.1% [95% CI, -0.2–0.1]; P = 0.359). Conclusions Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes.

Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Intima-Media Thickness: Systematic Review and Meta-Analysis

“…Three different GLP-1 RA drugs were investigated in the included studies: liraglutide [ 11 , 12 , 16 , 18 , 23 – 29 ], semaglutide [ 21 ], and exenatide [ 19 , 22 , 30 , 31 ]. Also, five different SGLT2i drugs were studied, including empagliflozin [ 32 , 36 , 38 , 42 ], ipragliflozin [ 33 , 39 , 41 ], tofogliflozin [ 34 , 40 ], dapagliflozin [ 35 – 37 , 42 ], and luseogliflozin [ 40 ]. The range of intervention periods for GLP-1 RA trials ranged from 4 months [ 12 , 13 , 21 , 26 ] to 3 years [ 29 ] and for SGLT2i trials was from 2 weeks [ 38 ] to 3.6 years [ 36 ].…”

Lack of impact of ipragliflozin on endothelial function in patients with type 2 diabetes: sub-analysis of the PROTECT study

“…In the PROTECT study, the primary endpoint in the main analysis was the change in the mean common carotid artery IMT from baseline to 24 months after the start of treatment; the results have already been reported [ 19 ]. The main objective of the present sub-analysis of the change in FMD in the brachial artery from baseline to 24 months after the start of treatment was to analyze one of the prespecified secondary endpoints [ 18 ].…”

“…The PROTECT study was a multicenter prospective study designed to test the inhibitory impact of an SGLT2 inhibitor on the development of atherosclerosis based on intima-media thickness over a 24-month follow-up period [ 18 , 19 ]. FMD of the brachial artery was assessed in some participants.…”

Rationale and design of an investigator-initiated, multicenter, prospective, placebo-controlled, double-blind, randomized trial to evaluate the effects of finerenone on vascular stiffness and cardiorenal biomarkers in type 2 diabetes and chronic kidney disease (FIVE-STAR)

“…Thus, lowering CAVI by about 1.0 can be equivalent to delaying the progression of vascular stiffness by approximately 20 years, which would be clinically meaningful. Based on the baseline data of our previous PROTECT study on patients with T2D, but not limited to those with CKD [ 22 ], the mean CAVI at baseline was about 9.0, with a standard deviation (SD) of approximately 1.5 (unpublished data). When using that value as a reference, lowering CAVI by 1.0 can correspond to CAVI with an SD of approximately 0.6.…”