Sodium‐glucose cotransporter‐2 inhibitor luseogliflozin added to glucagon‐like peptide 1 receptor agonist liraglutide improves glycemic control with bodyweight and fat mass reductions in Japanese patients with type 2 diabetes: A 52‐week, open‐label, single‐arm study

Abstract

Aims/IntroductionThe aim of the present study was to evaluate the safety and efficacy of luseogliflozin added to liraglutide monotherapy in Japanese individuals with type 2 diabetes.Materials and MethodsThis 52‐week, multicenter, open‐label, single‐arm clinical study enrolled Japanese patients who had inadequate glycemic control with diet/exercise and liraglutide monotherapy. Major efficacy end‐points included the changes from baseline in glycated hemoglobin, fasting plasma glucose and bodyweight. Body composition was also assessed in individuals who had access to bioelectrical impedance analysis. Safety assessments included adverse events, clinical laboratory tests, vital signs and 12‐lead electrocardiograms.ResultsOf 76 patients who received luseogliflozin, 62 completed the study. The changes from baseline in glycated hemoglobin, fasting plasma glucose, and bodyweight (mean ± SE) were −0.68 ± 0.10%, −32.1 ± 3.6 mg/dL and −2.71 ± 0.24 kg at week 52, respectively (all, P < 0.001 vs baseline). Luseogliflozin was associated with greater reductions in fat mass than lean mass at all measuring points (n = 22): fat vs lean mass changes (mean ± SE) at week 52 were −2.49 ± 0.45 kg (P < 0.001 vs baseline) and −0.44 ± 0.26 kg (P = 0.107 vs baseline), respectively. Insulin secretion and Matsuda Index were also improved at weeks 12 and 52 compared with baseline. Adverse events and adverse drug reactions occurred in 65.8 and 27.6% of patients, respectively. The overall safety profile, including frequency of hypoglycemia, was found to be consistent with those of previous studies and there were no new safety concerns.ConclusionsLuseogliflozin added to liraglutide was well tolerated, and improved glycemic control with bodyweight and fat mass reductions in Japanese type 2 diabetes patients.

Ipragliflozin, a sodium–glucose cotransporter 2 inhibitor, reduces bodyweight and fat mass, but not muscle mass, in Japanese type 2 diabetes patients treated with insulin: A randomized clinical trial

“…In the previous studies based on Japanese populations, 71-85% of BW reduction achieved with SGLT2 inhibitors resulted from fat loss as assessed with BIA [14][15][16][17] , and the reduction rates seemed to be dependent on the "treatment period." The studies 16,17 showed a trend toward a greater reduction rate at 6 or 12 months than that at 3 months. That would be another reason for the minor difference in the fat reduction Values are the meanstandard deviation for continuous variables of "baseline" and "24 weeks," and least squares meanstandard error for continuous variables of "change".…”

“…In the present study, 80% of BW reduction resulted from fat mass reduction (Figure ). In the previous studies based on Japanese populations, 71–85% of BW reduction achieved with SGLT2 inhibitors resulted from fat loss as assessed with BIA, and the reduction rates seemed to be dependent on the “treatment period.” The studies showed a trend toward a greater reduction rate at 6 or 12 months than that at 3 months. That would be another reason for the minor difference in the fat reduction rate in the same population.…”

Tofogliflozin decreases body fat mass and improves peripheral insulin resistance

“…Both basic and clinical studies have shown that insulin resistance is improved by the direct hypoglycaemic effect of SGLT2 inhibitors, as well as by alleviation of glucotoxicity and weight loss (reduction of BW and body fat) 1,[8][9][10][11] ; thus, it is clinically important to evaluate insulin resistance during SGLT2 inhibitor treatment.…”

Efficacy and safety of canagliflozin as add‐on therapy to a glucagon‐like peptide‐1 receptor agonist in Japanese patients with type 2 diabetes mellitus: A 52‐week, open‐label, phase IV study

“…In non‐Japanese patients with T2DM, this combination therapy resulted in improved glycaemic control and weight loss in randomized controlled trials . Although two long‐term, open‐label studies in Japanese patients with T2DM have been conducted, metabolic variables (body weight, blood pressure and lipid profile) warrant further investigation …”