Henagliflozein Proline

The role of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in diabetes treatment is expanding; however, few studies have investigated the efficacy and safety of combining SGLT2is with insulin pump therapy. Notably, there is a scarcity of high-quality, multicentre, clinical trials. Therefore, we aim to conduct a prospective multicentre, randomised, controlled, study to investigate whether treatment of type 2 diabetes patients with continuous subcutaneous insulin infusion (CSII) combined with henagliflozin can reduce the time required for blood glucose control, decrease total insulin requirements, mitigate blood glucose fluctuations and enhance beta-cell function.

In this inpatient, open-label, multicentre, randomised, controlled trial, 200 patients with type 2 diabetes who have not received hypoglycaemic drugs will be randomly allocated at a 1:1 ratio to either the henagliflozin combined with CSII group or the CSII group. The efficacy and safety of treatment in both groups will be compared. We will use a real-time continuous glucose monitoring system for blood glucose monitoring. The primary aim of this study is to compare the time (% time in range (TIR)) in the range of 3.9~10.0 mmol/L blood glucose between the two treatment groups. The secondary outcome measures will include comparisons of the two treatment groups with respect to the (a) time at TIR >70%; (b) mean amplitude of glycaemic excursions; (c) time below range; (d) total insulin dosage; and (e) time above range.

This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University and is to be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. The study will be disseminated through peer-reviewed publications and conference presentations.

NCT05677334.

Proline henagliflozin, a novel selective inhibitor of sodium glucose cotransporter 2, is a treatment for type 2 diabetes mellitus. We designed a parallel‐group, open‐label, and multicenter study to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety profiles of henagliflozin in Chinese subjects with varying degrees of liver dysfunction. Thirty‐two subjects were enrolled and divided into four groups based on liver function (normal liver function, mild, moderate, or severe liver dysfunction). The area under the plasma concentration from time zero to infinity of henagliflozin in subjects with mild liver dysfunction, moderate liver dysfunction, and severe liver dysfunction compared with normal liver function was increased by 137%, 197%, and 204%, respectively. The maximum plasma concentration was also increased by 123%, 129%, and 139%, respectively. PK parameters of three metabolites varied to different degrees in the liver dysfunction groups than in the normal liver function group. The mean accumulative excretion amounts and fraction of dose excreted in urine expressed as a percentage were all increased with the decrease of liver function. The PD parameters were significantly higher in liver dysfunction groups than those in the normal liver function group. However, the urine creatinine (UCr) was not significantly different among the groups. No notable adverse events or adverse drug reactions were observed. Due to the higher exposures in subjects with liver dysfunction, the benefit: risk ratio should be individually assessed because the long‐term safety profile and efficacy have not been specifically studied in this population.