SGLT2 inhibitor luseogliflozin bests DPP4 inhibitors among diabetes patients

The study revealed that at week 52, significantly higher proportion of patients in the luseogliflozin group showed improvement in ≥ 3 endpoints among five composite endpoints (weight, glycated hemoglobin, pulse rate, systolic blood pressure, and estimated glomerular filtration rate) compared to patients in the DPP-4i group regardless of age or BMI (body mass index).

Also, high-density lipoprotein-cholesterol and hepatic function were improved significantly with the luseogliflozin group compared with the DPP-4i group. The results also suggested the safety profile of luseogliflozin, regardless of BMI or age—or rather the frequency of adverse events—was numerically lower even in the older patients or non-obese patients.

There is a lack of evidence of a direct comparison between sodium-glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl-peptidase 4 inhibitors (DPP-4is), and no clear treatment rationale or strategy has been established using these drugs. Therefore, Masahiro Sugawara, Sugawara Clinic, Syakujii-machi, Nerima, Tokyo, Japan, and colleagues aimed to compare the safety and efficacy of DPP-4is and the SGLT2i luseogliflozin among patients with type 2 diabetes mellitus (T2DM).

For this purpose, the researchers enrolled 623 patients with T2DM who had not used antidiabetic agents or who had used antidiabetic agents other than DPP4 inhibitors and SGLT2 inhibitors after their written informed consent. The enrolled patients were randomly assigned to either the luseogliflozin or DPP-4i group and followed 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: eGFR, HbA1c, pulse rate, and systolic blood pressure.

The study led to the following findings:

• 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%).
• When stratified by body mass index (< 25 or ≥ 25 kg/m2) 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.

"The results suggest the criticality of evaluating multiple aspects regarding the effects of diabetes management," the authors concluded.

Reference:

Sugawara, M., Fukuda, M., Sakuma, I. et al. 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). Diabetes Ther (2023). https://doi.org/10.1007/s13300-023-01438-w