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).

INTRODUCTION: The effects of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) on quality of life (QOL) and treatment satisfaction have not been directly compared. This sub-analysis of a randomized-controlled trial with an SGLT2i, luseogliflozin, and DPP-4is compared their effects on QOL and treatment satisfaction of patients. METHODS: This study recruited 623 patients with type 2 diabetes mellitus who were drug-naïve or treated with antidiabetic agents other than SGLT2is and DPP-4is. The patients were randomized into luseogliflozin or DPP-4i group and followed for 52 weeks. This sub-analysis assessed QOL and treatment satisfaction using Oral Hypoglycemic Agent Questionnaire (OHA-Q) version 2 in the drug-naïve subgroup who were drug-naïve at baseline and with monotherapy with luseogliflozin or DPP-4i throughout the observation period (256 patients) at 24 and 52 weeks and in the add-on subgroup who were treated with OHAs other than SGLT2is and DPP-4is (204 patients) at baseline, 24 and 52 weeks. RESULTS: In the drug-naïve subgroup, total (50.8 ± 8.2 in luseogliflozin group and 53.1 ± 10.0 in DPP-4i group, p = 0.048) and somatic symptom scores (22.4 ± 5.0 in luseogliflozin group and 24.4 ± 5.8 in DPP-4i group, p = 0.005) at 52 weeks (but not at 24 weeks) were significantly higher in DPP-4i group than in luseogliflozin group. In add-on subgroup, changes in total (3.3 ± 7.8 in luseogliflozin group and 0.9 ± 7.6 in DPP-4i group, p = 0.030) and treatment convenience (1.2 ± 3.9 in luseogliflozin group and - 0.6 ± 4.2 in DPP-4i group, p = 0.002) from baseline to 24 weeks (but not at 52 weeks) were significantly greater in luseogliflozin group than in DPP-4i group. The QOL related to safety or glycemic control was comparable between the groups. CONCLUSIONS: Physicians should pay attention to side effects of SGLT2is to maintain the patients' QOL when SGLT2is are initiated or added-on. Add-on of luseogliflozin increased patients' QOL more than DPP-4is. Considering patients' QOL and treatment satisfaction is important for selecting SGLT2is or DPP-4is. TRIAL REGISTRATION: UMIN000030128 and jRCTs031180241.

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).

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/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. 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.

Vestibular Neuritis Following COVID-19 Vaccination: A Retrospective Study.

Objective To determine if the COVID-19 vaccine can cause vestibular neuritis (VN). Design Retrospective study. Setting Vertigo outpatient clinic of the Department of Otolaryngology JR Tokyo General Hospital. Participants: 378 patients who presented at the Vertigo clinic between July 2018 and March 2022 Results 23 out of 378 cases were diagnosed with vestibular neuritis. There was a significant seasonal bias of the onset of VN in 2021-3Q compared to other seasons. All 7 patients diagnosed with VN whose onset was 2021-3Q and 2021-4Q had received the BNT162b2 (Pfizer-BioNTech) vaccine within the previous 3 months and one patient diagnosed with VN whose onset was 2022-1Q had a history of COVID-19 infection six months earlier. Conclusions VN should be recognized as one of the side-effects of the BNT162b2 COVID-19 vaccination.

Efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes.

BACKGROUND: The aim of this study was to investigate the clinical efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes. METHODS: A total of 3,247 subjects treated with sitagliptin were retrospectively recruited. Glucose parameters were collected at baseline, and 1, 3 and 6 months after initiation of sitagliptin. In addition, we explored factors that can be used to predict sitagliptin-induced reduction in HbA1c using linear mixed effect model. Factors associated with hypoglycemic events were examined by logistic analyses. RESULTS: We analyzed the available data of 3,201 subjects (1,287 females). Treatment of sitagliptin significantly reduced HbA1c level from 7.44±1.20% at baseline to 6.73±0.99% at 6 months (P < 0.0001). Linear mixed effect model analyses demonstrated that reduction of HbA1c was associated with higher baseline HbA1c level, younger age, lower BMI and sitagliptin monotherapy. During this study, 82 cases of hypoglycemia were recorded. Logistic analyses indicated that hypoglycemic events were more frequent in female patients, and patients with low BMI, long history of type 2 diabetes, high HbA1c and on combination therapy experienced. Other adverse events were rare and mild. CONCLUSIONS: Sitagliptin is effective for diabetic management and generally well tolerated in Japanese patients with type 2 diabetes. This trial was registered with UMIN (no. 000004121).

Efficacy of pioglitazone on glycemic control and carotid intima-media thickness in type 2 diabetes patients with inadequate insulin therapy.

UNLABELLED: Aims/Introduction: The present study was designed to determine the effects of pioglitazone on glycemic control and atherosclerosis in patients with poorly controlled type 2 diabetes on insulin therapy. MATERIALS AND METHODS: The study was a prospective, randomized controlled trial involving 48 patients with inadequately controlled type 2 diabetes treated with insulin. We assigned patients to oral pioglitazone titrated from 15-30 mg (n = 22) or no pioglitazone (n = 26), to be taken in addition to their glucose-lowering drugs and other medications. Daily insulin doses and numbers were recorded during the study period. RESULTS: The adjusted mean glycosylated hemoglobin (HbA1c) values decreased significantly by 1.13 ± 1.50% and 0.55 ± 0.76% in the pioglitazone and control groups, respectively. Significant decrease of HbA1c level was observed in the pioglitazone group compared with the control group (P < 0.05). The insulin dose lowered by 0.04 ± 0.10 units/kg/day in the pioglitazone group and increased by 0.03 ± 0.10 units/kg/day in the control group (P < 0.05). The number of insulin injections decreased by 0.1 ± 0.6 times/day in the pioglitazone group and increased by 0.2 ± 0.4 times/day in the control group (P < 0.05). The carotid intima-media thickness estimated by B-mode echography was carried out in both groups and decreased significantly at the end-point only in the pioglitazone group, relative to the baseline. CONCLUSIONS: These findings show that pioglitazone is useful in improving glycemic control and preventing the progression of atherosclerosis in poorly-controlled type 2 diabetics on insulin therapy. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00064.x, 2010).