Overall Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitor Luseogliflozin Versus Dipeptidyl-Peptidase 4 Inhibitors: Multicenter, Open-Label, Randomized-Controlled Trial (J-SELECT study)

Abstract

Introduction Evidence of a direct comparison between dipeptidyl-peptidase 4 inhibitors (DPP-4is) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) remains lacking, and no clear treatment strategy or rationale has been established using these drugs. This study aimed to compare the overall efficacy and safety of DPP-4is and the SGLT2i luseogliflozin in patients with type 2 diabetes mellitus (T2DM). Methods Patients with T2DM who had not used antidiabetic agents or who had used antidiabetic agents other than SGLT2is and DPP-4is were enrolled in the study after written informed consent had been obtained. The enrolled patients were subsequently randomly assigned to either the luseogliflozin or DPP-4i group and followed up for 52 weeks. The primary (composite) endpoint was the proportion of patients who showed improvement in ≥ 3 endpoints among the following five endpoints from baseline to week 52: glycated hemoglobin (HbA1c), weight, estimated glomerular filtration rate (eGFR), systolic blood pressure, and pulse rate. Results A total of 623 patients were enrolled in the study and subsequently randomized to either the luseogliflozin or DPP-4i groups. The proportion of patients who showed improvement in ≥ 3 endpoints at week 52 was significantly higher in the luseogliflozin group (58.9%) than in the DPP-4i group (35.0%) ( p < 0.001). When stratified by body mass index (BMI) (< 25 or ≥ 25 kg/m 2 ) or age (< 65 or ≥ 65 years), regardless of BMI or age, the proportion of patients who achieved the composite endpoint was significantly higher in the luseogliflozin group than in the DPP-4i group. Hepatic function and high-density lipoprotein-cholesterol were also significantly improved in the luseogliflozin group compared with the DPP-4i group. The frequency of non-serious/serious adverse events did not differ between the groups. Conclusion This study showed the overall efficacy of luseogliflozin compared with DPP-4is over the mid/long term, regardless of BMI or age. The results suggest the importance of assessing multiple aspects regarding the effects of diabetes management. Trial Registration Number jRCTs031180241. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-023-01438-w.

Effect of Luseogliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, and Dipeptidyl-Peptidase 4 Inhibitors on the Quality-of-Life and Treatment Satisfaction of Patients With Type 2 Diabetes Mellitus: A Subanalysis of a Multicenter, Open-Label, Randomized-Controlled Trial (J-SELECT Study)

“…The J-SELECT study was a multicenter, open-label, randomized-controlled trial. The details have been published in our previous paper [ 14 ]. Patient enrollment was conducted between January 2018 and November 2020 at 88 medical institutions in Japan (Supplementary Materials Table 1 ), and each enrolled patient was followed for 12 months.…”

“…Exclusion criteria were (1) patients who used insulin or GLP-1 analogs within 8 weeks before consenting and (2) patients with cardiac disease (myocardial infarction, cerebral infarction, or stroke), severe liver disease, renal disease, unstable hypertension or dyslipidemia, dehydration, urinary tract infection, genital infection, or geriatric syndrome (sarcopenia, cognitive dysfunction, impairment in activities of daily living, etc.). The inclusion and exclusion criteria have been described in detail in our previous paper [ 14 ]. The registered patients were randomly assigned to the luseogliflozin and DPP-4i groups in an approximately 1:1 ratio.…”

“…The patients were followed up to baseline (week 0) before the initiation and 2, 24, and 52 weeks after the initiation of the study agents. The details of observation schedules and items have been described in our previous paper [ 14 ].…”

“…Secondary endpoints included blood tests and urine tests. A full list of the secondary endpoints and the results of the primary endpoint and laboratory test-related secondary endpoints has been reported in our previous paper [ 14 ]. As a secondary endpoint, the OHA-Q version 2 [ 3 , 4 ] was administered to the enrolled patients 0, 24, and 52 weeks after initiation, with permission for use from Hitoshi Ishii [ 3 ].…”

“…However, no study had directly compared the effect of DPP-4is and SGLT2is, especially in terms of QOL and treatment satisfaction of patients with type 2 diabetes mellitus. The J-SELECT study demonstrated the overall and multiple aspects of the efficacy of luseogliflozin compared with DPP-4is in the mid-/long-term, regardless of body mass index (BMI) or age [ 14 ]. This article reports the results of a sub-analysis of the J-SELECT study comparing patient QOL and treatment satisfaction between that with DPP-4is and luseogliflozin.…”