Efficacy and tolerability of oral semaglutide in Japanese patients with type 2 diabetes mellitus: Analysis report from diabetes specialist clinics.

INTRODUCTION: Glucagon-like peptide 1 receptor agonists (GLP1Ras) have emerged as pivotal agents in diabetes management and organ protection. However, their use is limited due to the necessity for injectable administration. The advent of the first oral GLP1Ra (oral semaglutide) in Japan since 2021 is expected to expand its usage. The aim of this study is to survey the efficacy and tolerability of oral semaglutide in clinical practice. MATERIALS AND METHODS: We retrospectively analyzed 120 outpatients diagnosed with type 2 diabetes mellitus who had received oral semaglutide for >6 months. Changes in clinical parameters during oral semaglutide treatment from baseline to 12 months were analyzed. The inverse probability weighting method using the propensity score was used to evaluate the differences in clinical parameters at 6 months after treatment, based on the patients' obesity levels. RESULTS: Body weight (BW), glycated hemoglobin A1c (HbA1c), and alanine aminotransferase (ALT) levels at baseline decreased significantly after treatment compared with those at 12 months (P < 0.001, P < 0.001, and P = 0.03, respectively). The patients were divided into two groups using a cutoff baseline body mass index (BMI) of 30.3 kg/m2. Although no significant difference was observed, changes in body weight and HbA1c indicated a potentially greater decrease in the BMI ≧ 30.3 group than that in the BMI < 30.3 group (P = 0.07 and 0.13, respectively). Among 206 registered patients, 25 (12.1%) discontinued oral-semaglutide treatment owing to adverse effects, including gastrointestinal symptoms. CONCLUSIONS: Oral semaglutide treatment demonstrates efficacy and tolerability for managing type 2 diabetes mellitus in Japan. Significant improvements in metabolic factors induced by oral semaglutide are anticipated, particularly in obese patients.

Luseogliflozin Additively Enhances the Glucose-Lowering Effect of an Incretin Modulator in a High-Carbohydrate Diet.

Background and objectives Sodium/glucose co-transporter 2 inhibitors (SGLT2i) have been shown to have a glucose-lowering effect related to carbohydrate intake. It has also been reported that the combined effect of incretin modulators and SGLT2i is useful in improving blood glucose and reducing blood glucose variability. However, there have been no reports examining the effects of these two drugs together and while considering carbohydrate intake in an outpatient setting. In the present study, Hi-Speed Food Analysis was used to assess the exact intake of carbohydrates, and the glucose-lowering effects of luseogliflozin, an SGLT2i, and incretin modulators were examined under high- and low-carbohydrate intakes. Methods Thirty-five enrolled diabetic patients continued their regular medications for one week. All patients took luseogliflozin in the second week for seven days. During the two weeks, ingested carbohydrates were accurately calculated by Hi-Speed Food Analysis. The glucose-lowering effect of luseogliflozin with and without incretin modulators was checked according to the amount of ingested carbohydrates. A general linear model (GLM) was used to analyze the effect of luseogliflozin with or without an incretin modulator, with carbohydrate intake as a confounding factor. Results Luseogliflozin had an additive effect in patients who had taken the incretin modulator. There was a significant decrease in the time above range (TAR) with glucose above 140 mg/dL as expressed as TAR(min140), and this effect was affected by carbohydrate intake. Conclusions The glucose-lowering effect of luseogliflozin was enhanced with high-carbohydrate intake more than with low-carbohydrate intake. In this study, the observed number was small; however, combined treatment with an incretin modulator and luseogliflozin had an additive effect in high- versus low-carbohydrate intake, indicating the possible effectiveness of the combined therapy.

Relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetic patients (JDDM38).

AIMS/INTRODUCTION: We carried out an observational cohort study to examine the relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetics. MATERIALS AND METHODS: We analyzed the CoDiC(®) database of the Japan Diabetes Data Management Study Group across 67 institutions in Japan. In a total of 3,698 drug-naïve patients who were initiated with metformin, dipeptidyl peptidase-4 inhibitor (DPP-4i) or sulfonylurea (SU) from 2007 to 2012, we evaluated body mass index (BMI) and hemoglobin A1c (HbA1c). The patients were stratified according to their clinical features, and matched using a propensity score to adjust for baseline factors. RESULTS: HbA1c was reduced with all drugs, with the largest effect elicited by DPP-4i and the smallest by SU (P = 0.00). HbA1c increased with SU after 6 months in the patients stratified by an age-of-onset of <50 years (P = 0.00). BMI increased with SU in the patients stratified by a BMI of <25 (P = 0.00), and decreased with metformin in the patients with a BMI >25 (P = 0.00). The reduction in HbA1c was larger in patients with HbA1c of ≥8%, compared with that in patients with HbA1c of <8% (P = 0.00). HbA1c during the study period was higher in patients who were added to or swapped with other drug(s), than in patients continued on the original drug (P = 0.00). CONCLUSIONS: The effect on bodyweight and glycemic control differed among metformin, DPP-4i and SU, and the difference was associated with clinical features.

Liraglutide Versus Sitagliptin in a 24-week, Multicenter, Open-label, Randomized, Parallel-group Study in Japanese Type 2 Diabetes Mellitus Patients Responding Inadequately to a Sulfonylurea and/or One or Two Other Oral Antidiabetic Drugs (JDDM 33).

OBJECTIVE: Liraglutide (glucagon-like peptide-1 [GLP-1] receptor agonist) and sitagliptin (dipeptidyl peptidase-4 inhibitor) are approved in Japan for treating type 2 diabetes mellitus (T2DM). We compared the efficacy and safety of adding liraglutide or sitagliptin to a sulfonylurea in Japanese T2DM patients. METHODS: Patients aged 18 to <80 years with hemoglobin A1c (HbA1c; National Glycohemoglobin Standardization Program [NGSP]) of 6.9-9.4%, body mass index ≤35 kg/m(2), and treatment with a sulfonylurea and/or one or two non-sulfonylurea oral antidiabetic drugs for greater than or equal to eight weeks before enrollment were eligible. Patients were randomized in an open-label manner to either 0.9 mg/day liraglutide (n = 50) or 50-100 mg/day sitagliptin (n = 49) and were treated for 24 weeks. Non-sulfonylureas were discontinued before randomization. Patients using other oral antidiabetic drugs started sulfonylurea treatment. The primary endpoint was the change in HbA1c from baseline to Week 24. RESULTS: HbA1c decreased in both groups, and the reduction was significantly greater throughout in the liraglutide group except for Week 24 (0.59 ± 0.80 vs. 0.24 ± 0.94%; P = 0.0525). Fasting plasma glucose (FPG) decreased significantly in the liraglutide group compared with the sitagliptin group (-21.15 ± 31.22 vs. +0.46 ± 39.39 mg/dL; P = 0.0014). Homeostasis model assessment of ß cell function and C-peptide increased significantly in the liraglutide group but not in the sitagliptin group. Hypoglycemic symptoms and adverse events occurred in four and nine patients, respectively, in the liraglutide group, and in two and five patients, respectively, in the sitagliptin group. CONCLUSION: Treatment with liraglutide or sitagliptin together with a sulfonylurea improved HbA1c in Japanese T2DM patients in primary care. Both drugs were associated with low rates of adverse events and hypoglycemia. The improvement in ß cell function probably contributed to the improvement in glycemic control in the liraglutide group.