Real-world effectiveness of imeglimin in patients with type 2 diabetes: A retrospective longitudinal study in Japan.

OBJECTIVE: To examine the real-world effects of imeglimin on glycemic control and other metabolic factors in patients with type 2 diabetes (T2DM). METHODS: A retrospective longitudinal study was conducted based on a chart review. We recruited patients with T2DM who took imeglimin continuously for at least 3 months. Data on various metabolic parameters were collected at the first prescription of imeglimin and at 3, 6 and 12 months after the initiation of imeglimin. Statistical comparisons were performed using paired t-tests. RESULTS: 68 patients were eligible for this study. HbA1c decreased by 0.7 % at 3 months, 1.1 % at 6 months and 1.0 % by 12 months after the initiation of imeglimin. The decreases in HbA1c were observed regardless of age, gender, body mass index, duration of diabetes, renal function and concomitant use of hypoglycemic agents. There were also significant decreases in body weight, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and non-HDL-C during imeglimin treatment. CONCLUSIONS: This is the first report showing the long-term effects of imeglimin in a real-world setting. We confirmed the glucose-lowering effects of imeglimin. Furthermore, favorable effects of imeglimin on body weight and serum lipids were also suggested.

Is children's mental health an important function of newly national organization for health crisis management in Japan?

This review discussed analyzing information dissemination and activities related to mental health conducted by the Centers of Disease Control and Prevention (CDC), considering their application in Japan, and disseminating them to the public is necessary for the Japanese New Center for Health Control. The Japanese government also explores the Japanese New Center For Health Control in addressing children's mental health issues potentially under the Japan health crisis. The findings underscore the urgency of prioritizing children's mental health and implementing effective strategies to mitigate the long-term effects of the COVID-19 pandemic.

Effects of Once-Weekly Semaglutide on Cardiovascular Risk Factors and Metabolic Dysfunction-Associated Steatotic Liver Disease in Japanese Patients with Type 2 Diabetes: A Retrospective Longitudinal Study Based on Real-World Data.

Once-weekly semaglutide is a widely used glucagon-like peptide-1 receptor agonist (GLP-1RA) used for the treatment of type 2 diabetes (T2D). In clinical trials, semaglutide improved glycemic control and obesity, and reduced major cardiovascular events. However, the reports are limited on its real-world efficacy relating to various metabolic factors such as dyslipidemia or metabolic dysfunction-associated steatotic liver disease (MASLD) in Asian patients with T2D. In our retrospective longitudinal study, we selected patients with T2D who were given once-weekly semaglutide and compared metabolic parameters before and after the start of semaglutide. Seventy-five patients were eligible. HbA1c decreased significantly, by 0.7-0.9%, and body weight by 1.4-1.7 kg during the semaglutide treatment. Non-HDL cholesterol decreased significantly at 3, 6 and 12 months after the initiation of semaglutide; LDL cholesterol decreased at 3 and 6 months; and HDL cholesterol increased at 12 months. The effects on body weight, HbA1c and lipid profile were pronounced in patients who were given semaglutide as a first GLP-1RA (GLP-1R naïve), whereas improvements in HbA1c were also observed in patients who were given semaglutide after being switched from other GLP-1RAs. During a 12-month semaglutide treatment, the hepatic steatosis index (HSI) tended to decrease. Moreover, a significant decrease in the AST-to-platelet ratio index (APRI) was observed in GLP-1RA naïve patients. Our real-world study confirmed the beneficial effects of once-weekly semaglutide, namely, improved body weight, glycemic control and atherogenic lipid profile. The beneficial effects on MASLD were also suggested.

Renal Function Improvement With Glucagon-Like Peptide-1 Receptor Agonist in a Patient With Type 2 Diabetes.

Diabetic kidney disease (DKD) includes hypertensive nephrosclerosis, aging, obesity, and atherosclerosis-related renal diseases, in addition to classical diabetic nephropathy. Sodium-glucose co-transporter 2 inhibitors (SGLT2is) have been approved for diabetic and non-diabetic patients at risk of chronic kidney disease progression. As the main mechanism for SGLT2i-mediated improvement of renal function, the normalization of tubulo-glomerular feedback (TGF) has been proposed. Enhanced TGF and resulting glomerular hypertension are observed in diabetic patients, and SGLT2is normalize TGF, reducing the intraglomerular pressure, which may reduce albuminuria and improve renal function. A type 2 diabetic patient with DKD complicated with hypertensive nephrosclerosis, whose renal function was deteriorated by SGLT2i and improved by glucagon-like peptide-1 receptor agonists (GLP-1RAs), was presented. In patients with hypertensive nephrosclerosis such as this case, the normalization of TGF by SGLT2i may further reduce afferent arteriolar blood flow which may worsen glomerular ischemia, resulting in deterioration of renal function. GLP-1RAs have no effect on TGF and have multiple effects to improve vascular endothelial function, which may be associated with an improvement in renal function in this patient.

Prediction of future insulin-deficiency in glutamic acid decarboxylase autoantibody enzyme-linked immunosorbent assay-positive patients with slowly-progressive type 1 diabetes.

AIMS/INTRODUCTION: This study aimed to identify risk factors that contribute to the progression of slowly-progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin-dependent state. MATERIALS AND METHODS: We selected 60 slowly-progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: Compared with the non-progressor group (fasting C-peptide [F-CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F-CPR levels and a higher prevalence of insulinoma-associated antigen-2 autoantibodies (IA-2A). The PPV of RIA-GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis <47 years, BMI <22.6 kg/m2, F-CPR <1.41 ng/mL and IA-2A positivity, respectively. In contrast, the PPV of ELISA-GADA (71.8%) remained the same at 73.1% in the high titer group (≥180 U/mL), but increased to 81.8, 82.4 and 79.0% when evaluated in conjunction with age at diagnosis, BMI and F-CPR level, respectively. CONCLUSIONS: Our findings show that, unlike RIA-GADA, ELISA-GADA shows no association between GADA titers and the risk of progression to an insulin-dependent state. The PPV improves when age at diagnosis, BMI and F-CPR levels are considered in combination.

A Possible Therapeutic Application of the Selective Inhibitor of Urate Transporter 1, Dotinurad, for Metabolic Syndrome, Chronic Kidney Disease, and Cardiovascular Disease.

The reabsorption of uric acid (UA) is mainly mediated by urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in the kidneys. Dotinurad inhibits URAT1 but does not inhibit other UA transporters, such as GLUT9, ATP-binding cassette transporter G2 (ABCG2), and organic anion transporter 1/3 (OAT1/3). We found that dotinurad ameliorated the metabolic parameters and renal function in hyperuricemic patients. We consider the significance of the highly selective inhibition of URAT1 by dotinurad for metabolic syndrome, chronic kidney disease (CKD), and cardiovascular disease (CVD). The selective inhibition of URAT1 by dotinurad increases urinary UA in the proximal tubules, and this un-reabsorbed UA may compete with urinary glucose for GLUT9, reducing glucose reabsorption. The inhibition by dotinurad of UA entry via URAT1 into the liver and adipose tissues increased energy expenditure and decreased lipid synthesis and inflammation in rats. Such effects may improve metabolic parameters. CKD patients accumulate uremic toxins, including indoxyl sulfate (IS), in the body. ABCG2 regulates the renal and intestinal excretion of IS, which strongly affects CKD. OAT1/3 inhibitors suppress IS uptake into the kidneys, thereby increasing plasma IS, which produces oxidative stress and induces vascular endothelial dysfunction in CKD patients. The highly selective inhibition of URAT1 by dotinurad may be beneficial for metabolic syndrome, CKD, and CVD.

Association between comorbidities associated with diabetes and higher-level functional status in older patients with type 2 diabetes mellitus: a cross sectional study.

PURPOSE: To investigate the association between comorbidities associated with diabetes and higher-level functional status as well as the relationship between comorbidities associated with diabetes and higher-level functional status in older patients with type 2 diabetes mellitus who have better social networks. METHODS: Participants were outpatients with type 2 diabetes aged ≥ 65 years, excluding individuals with severe cardiovascular or respiratory illness, hyperglycaemic crisis, type 1 diabetes, or diabetic foot. The Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) was used to evaluate the higher-level functional status. A TMIG-IC score of ≤ 9, instrumental activities of daily living (IADL) ≤ 4, intellectual activity or social role ≤ 3 were defined as decline in higher-level functional status. The comorbidities investigated included peripheral neuropathy, retinopathy, nephropathy, cognitive impairment, depression, frailty, sarcopenia, low muscle strength, stroke, heart disease, and arthritis. RESULTS: The analysis included 198 patients (mean age 75.9 ± 5.7 years, male 60.1%). After adjusting for potential confounders, depression was associated with TMIG-IC (Prevalence ratio (PR) 2.34, 95% confidence interval (CI) 1.44-3.82), low muscle strength was associated with IADL (PR 2.85, 95% CI 1.30-6.27), and frailty was associated with intellectual activity (PR 1.38, 95% CI 1.10-1.74). In the model with social networks added as a confounder, the relationship between depression or low muscle strength and higher-level functional status was not statistically significant. CONCLUSION: Comorbidities of depression and low muscle strength for older patients with type 2 diabetes mellitus increase the risk of malfunctioning of higher-level functional status. Increased interactions with family, friends and neighbours may reduce this event.

Prescription of anti-influenza drugs in Japan, 2014-2020: A retrospective study using open data from the national claims database.

BACKGROUND: Both physicians and patients are proactive towards managing seasonal influenza in Japan and six drugs are approved. Although many countries have national influenza surveillance systems, data on nationwide prescription practices of anti-influenza drugs are lacking. Therefore, we aimed to clarify the status of anti-influenza drug use in Japan by analyzing real-world data. METHODS: This retrospective study analyzed open data from the National Database of Health Insurance Claims and Specific Health Checkups, which covers most claims data from national health insurance. We estimated the annual number of patients prescribed anti-influenza drugs, which drugs they were prescribed, the patients' age and sex distribution, drug costs, and regional disparities for the period 2014-2020. RESULTS: For 2014-2019, an estimated 6.7-13.4 million patients per year were prescribed anti-influenza drugs, with an annual cost of 22.3-48.0 billion JPY (Japanese Yen). In addition, 21.1-32.0 million rapid antigen tests were performed at a cost of 30.1-47.1 billion JPY. In 2017, laninamivir was the most frequently prescribed anti-influenza drug (48%), followed by oseltamivir (36%), while in 2018, the newly introduced baloxavir accounted for 40.8% of prescriptions. After the emergence of COVID-19, the estimated number of patients prescribed anti-influenza drugs in 2020 dropped to just 14,000. In 2018, 37.6% of prescriptions were for patients aged < 20 years compared with 12.2% for those aged ≥ 65 years. Prescriptions for inpatients accounted for 1.1%, and the proportion of prescriptions for inpatients increased with age, with men were more likely than women to be prescribed anti-influenza drugs while hospitalized. CONCLUSIONS: Based on our clarification of how influenza is clinically managed in Japan, future work should evaluate the clinical and economic aspects of proactively prescribing anti-influenza drugs.

Metabolic-Dysfunction-Associated Steatotic Liver Disease-Its Pathophysiology, Association with Atherosclerosis and Cardiovascular Disease, and Treatments.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease that affects more than a quarter of the global population and whose prevalence is increasing worldwide due to the pandemic of obesity. Obesity, impaired glucose metabolism, high blood pressure and atherogenic dyslipidemia are risk factors for MASLD. Therefore, insulin resistance may be closely associated with the development and progression of MASLD. Hepatic entry of increased fatty acids released from adipose tissue, increase in fatty acid synthesis and reduced fatty acid oxidation in the liver and hepatic overproduction of triglyceride-rich lipoproteins may induce the development of MASLD. Since insulin resistance also induces atherosclerosis, the leading cause for death in MASLD patients is cardiovascular disease. Considering that the development of cardiovascular diseases determines the prognosis of MASLD patients, the therapeutic interventions for MASLD should reduce body weight and improve coronary risk factors, in addition to an improving in liver function. Lifestyle modifications, such as improved diet and increased exercise, and surgical interventions, such as bariatric surgery and intragastric balloons, have shown to improve MASLD by reducing body weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to improve coronary risk factors and to suppress the occurrence of cardiovascular diseases. Both SGLT2i and GLP-1 have been reported to improve liver enzymes, hepatic steatosis and fibrosis. We recently reported that the selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator pemafibrate improved liver function. PPARα agonists have multiple anti-atherogenic properties. Here, we consider the pathophysiology of MASLD and the mechanisms of action of such drugs and whether such drugs and the combination therapy of such drugs could be the treatments for MASLD.

Postprandial Hyperlipidemia: Its Pathophysiology, Diagnosis, Atherogenesis, and Treatments.

Postprandial hyperlipidemia showing postprandial increases in serum triglyceride (TG) is associated with the development of atherosclerotic cardiovascular disease (ASCVD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed; however, this test is very time-consuming and is difficult to perform. Elevated serum TG levels reflect an increase in TG-rich lipoproteins (TRLs), such as chylomicrons (CM), very low-density lipoproteins (VLDL), and their remnants (CM remnants [CMRs] and VLDL remnants [VLDLRs]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurement of apo B48, which is a constituent of CM and CMR; non-fasting TG, which includes TG content in all lipoproteins including CM and CMR; non-high-density lipoprotein cholesterol (non-HDL-C), which includes TRLs and low-density lipoprotein; and remnant cholesterol are useful to reveal the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an inducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with postprandial hyperlipidemia have various atherogenic properties such as induction of inflammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss, and exercise positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, fenofibrate, bezafibrate, ezetimibe, and eicosapentaenoic acid have been shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide 1 analogues have been shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments. However, there are some problems with the diagnosis for postprandial hyperlipidemia. Postprandial hyperlipidemia cannot be specifically defined by measures such as TG levels 2 h after a meal. To study interventions for postprandial hyperlipidemia with the outcome of preventing the onset of ASCVD, it is necessary to define postprandial hyperlipidemia using reference values such as IGT.

A Significant Effect of Pemafibrate on Hepatic Steatosis and Fibrosis Indexes in Patients With Hypertriglyceridemia.

Background: We previously reported that the selective peroxisome proliferator-activated receptor alpha modulator, pemafibrate, significantly reduced serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) and significantly increased serum albumin levels at 3, 6 and 12 months after the start of pemafibrate, with an improvement of atherogenic dyslipidemia, in patients with hypertriglyceridemia. Methods: We performed a post hoc analysis of our previous data obtained from patients with hypertriglyceridemia who had been prescribed pemafibrate continuously for 1 year or longer. We compared the indexes for hepatic steatosis (hepatic steatosis index (HSI)) and fibrosis (nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), AST to platelet ratio index (APRI) and FIB-4 index) at baseline with the data at 1 year after the start of pemafibrate. Results: Pemafibrate significantly reduced HSI at 1 year after the start of pemafibrate. NFS did not show a significant change after 1 year. However, APRI was significantly reduced by pemafibrate after 1 year. FIB-4 index significantly decreased in patients with baseline FIB-4 index ≥ 1.45 at 1 year after the start of pemafibrate. HSI at baseline tended to be negatively correlated with change in HSI after 1 year. There was no significant correlation between NFS at baseline and change in this score after 1 year. APRI and FIB-4 index at baseline were significantly and negatively correlated with changes in APRI and FIB-4 index at 1 year after the start of pemafibrate. Conclusions: The 1-year pemafibrate treatment improved hepatic steatosis and fibrosis indexes in patients with hypertriglyceridemia.

Association of the use of psychotropic drugs with hospitalization, cardiovascular events, and mortality in patients with type 2 diabetes: a propensity score-matched cohort study.

Background: Use of psychotropic drugs (PD) may be associated with impairment of physical function. However, few studies have assessed the impact of PD on health outcomes in patients with type 2 diabetes. This study aimed to examine the associations between psychotropic drug use and handgrip strength (HGS) and between the use of PD and hospitalization in patients with type 2 diabetes. Methods: From April 2013 to December 2015, we conducted a retrospective cohort study in patients with type 2 diabetes at the National Center for Global Health and Medicine Kohnodai Hospital. Patients aged 20 years and over who can measure HGS were included. All participants received nutritional guidance regarding diet therapy for type 2 diabetes at baseline. Nonpsychotropic drug users were matched one-to-one with the PD users using propensity score matching method with respect to their baseline covariates. The differences in HGS and the number of patients who had hospitalizations during the study period were examined. By Cox proportional hazard regression analysis, the association between the use of PD and repeated hospitalizations was estimated. Results: A total of 1,282 patients were enrolled and followed up for 2.36 ± 0.73 years. In the propensity score matching cohort, HGS was significantly lower (p = 0.006) in PD users than non-PD users. PD users had more hospitalizations than non-PD users. Cox proportional hazard regression analysis confirmed the association of repeated hospitalizations with the use of PD (hazard ratio = 2.138; 95% confidence interval, 1.144-3.995, p = 0.017)). In addition, HGS was significantly and inversely correlated with the number of hospitalizations (r = -0.143, p = 0.013). Conclusions: The use of PD could increase the risk of repeated hospitalizations. Skeletal muscle may play a role in reducing the risk of hospitalization in patients who are treated with PD.

Significance of Endothelial Dysfunction Amelioration for Sodium-Glucose Cotransporter 2 Inhibitor-Induced Improvements in Heart Failure and Chronic Kidney Disease in Diabetic Patients.

Beyond lowering plasma glucose levels, sodium-glucose cotransporter 2 inhibitors (SGLT2is) significantly reduce hospitalization for heart failure (HF) and retard the progression of chronic kidney disease (CKD) in patients with type 2 diabetes. Endothelial dysfunction is not only involved in the development and progression of cardiovascular disease (CVD), but is also associated with the progression of CKD. In patients with type 2 diabetes, hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia induce the development of endothelial dysfunction. SGLT2is have been shown to improve endothelial dysfunction, as assessed by flow-mediated vasodilation, in individuals at high risk of CVD. Along with an improvement in endothelial dysfunction, SGLT2is have been shown to improve oxidative stress, inflammation, mitochondrial dysfunction, glucotoxicity, such as the advanced signaling of glycation end products, and nitric oxide bioavailability. The improvements in endothelial dysfunction and such endothelium-derived factors may play an important role in preventing the development of coronary artery disease, coronary microvascular dysfunction and diabetic cardiomyopathy, which cause HF, and play a role in retarding CKD. The suppression of the development of HF and the progression of CKD achieved by SGLT2is might have been largely induced by their capacity to improve vascular endothelial function.

Glucose-Lowering Effects of Imeglimin and Its Possible Beneficial Effects on Diabetic Complications.

Mitochondrial dysfunction is a prominent pathological feature of type 2 diabetes, which contributes to ß-cell mass reduction and insulin resistance. Imeglimin is a novel oral hypoglycemic agent with a unique mechanism of action targeting mitochondrial bioenergetics. Imeglimin reduces reactive oxygen species production, improves mitochondrial function and integrity, and also improves the structure and function of endoplasmic reticulum (ER), changes which enhance glucose-stimulated insulin secretion and inhibit the apoptosis of ß-cells, leading to ß-cell mass preservation. Further, imeglimin inhibits hepatic glucose production and ameliorates insulin sensitivity. Clinical trials into the effects of imeglimin monotherapy and combination therapy exhibited an excellent hypoglycemic efficacy and safety profile in type 2 diabetic patients. Mitochondrial impairment is closely associated with endothelial dysfunction, which is a very early event in atherosclerosis. Imeglimin improved endothelial dysfunction in patients with type 2 diabetes via both glycemic control-dependent and -independent mechanisms. In experimental animals, imeglimin improved cardiac and kidney function via an improvement in mitochondrial and ER function or/and an improvement in endothelial function. Furthermore, imeglimin reduced ischemia-induced brain damage. In addition to glucose-lowering effects, imeglimin can be a useful therapeutic option for diabetic complications in type 2 diabetic patients.

Measurement of cholesterol levels of lipoprotein subclasses in human serum using anion-exchange high-performance liquid chromatography with a linear concentration gradient of sodium perchlorate.

BACKGROUND: Relationships between the subclasses of high-density lipoprotein (HDL) or low-density lipoprotein (LDL) and the risk of atherosclerotic cardiovascular disease have been studied, and using various methods, such as ultracentrifugation, electrophoresis, and nuclear magnetic resonance, for analysing lipoprotein subclasses. We established a method for HDL and LDL subclasses using anion-exchange high-performance liquid chromatography (AEX-HPLC) with a linear concentration gradient of sodium perchlorate (NaClO4). METHOD: In the AEX-HPLC, the subclasses of HDL and LDL were separated, and detected using a post-column reactor with an enzymatic cholesterol reagent, that contained cholesterol esterase, cholesterol oxidase, and peroxidase as major ingredients. LDL subclasses were divided based on the absolute value of first-derivative chromatogram. RESULT: Three HDL subclasses, HDL-P1, HDL-P2, and HDL-P3, and three LDL subclasses, LDL-P1, LDL-P2, and LDL-P3, were separated by AEX-HPLC, and detected in order. The major components of HDL-P2 and HDL-P3 were HDL3 and HDL2, respectively. The linearity was determined for each lipoprotein subclass. The coefficients of variation of cholesterol concentration of the subclasses for within-day assay (n = 10) and between-day assay (n = 10) ranged between 3.08-8.94% and 4.52-9.97%, respectively. Cholesterol levels in HDL-P1 of diabetic patients were positively correlated with oxidized LDL levels (r = 0.409, p = 0.002). Moreover, cholesterol levels in LDL-P2 and LDL-P3 were positively correlated with oxidized LDL levels (r = 0.393, p = 0.004 and r = 0.561, p < 0.001, respectively). CONCLUSION: AEX-HPLC may be highly suitable as an assay to clinically assess lipoprotein subclasses.

Effects of sodium glucose cotransporter 2 inhibitors and pioglitazone on FIB-4 index in metabolic-associated fatty liver disease.

BACKGROUND: The antidiabetic drugs sodium glucose cotransporter 2 inhibitors (SGLT2is) and thiazolidinediones have beneficial effects on the liver dysfunction of patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus (T2DM). We aimed to determine the efficacy of these drugs for the treatment of liver disease in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and T2DM. METHODS: We undertook a retrospective study of 568 patients with MAFLD and T2DM. Of these, 210 were treating their T2DM with SGLT2is (n = 95), 86 with pioglitazone (PIO), and 29 with both. The primary outcome was the change in Fibrosis-4 (FIB-4) index between baseline and 96 weeks. RESULTS: At 96 weeks, the mean FIB-4 index had significantly decreased (from 1.79 ± 1.10-1.56 ± 0.75) in the SGLT2i group, but not in the PIO group. The aspartate aminotransferase to platelet ratio index, serum aspartate and alanine aminotransferase (ALT), hemoglobin A1c, and fasting blood sugar significantly decreased in both groups (ALT: SGLT2i group, -17 ± 3 IU/L; PIO group, -14 ± 3 IU/L). The bodyweight of the SGLT2i group decreased, but that of the PIO group increased (-3.2 kg and +1.7 kg, respectively). When the participants were allocated to two groups according to their baseline ALT (>30 IU/L), FIB-4 index significantly decreased in both groups. In patients taking pioglitazone, the addition of SGLT2i improved liver enzymes but not FIB-4 index for 96 weeks. CONCLUSIONS: Treatment with SGLT2i causes a larger improvement in FIB-4 index than PIO in patients with MAFLD over 96 weeks.

Periodic health checkups reduce the risk of hospitalization in patients with type 2 diabetes.

Introduction: Periodic health checkups (PHCs) represent a unique system in Japan that is useful for the early detection of lifestyle-related diseases and cardiovascular diseases (CVDs). This study aims to investigate the association of PHCs with the hospitalization risk of patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective cohort study was conducted from April 2013 to December 2015 and included participant information such as CVD history, lifestyle, and whether PHC was conducted in addition to regular medical examinations. Difference in clinical data between patients with and without PHC was examined. Furthermore, Cox regression analysis was performed to investigate the independent association of PHCs with hospitalization. Results: Herein, 1,256 patients were selected and followed up for 2.35 ± 0.73 years. In the PHC group, body mass index, waist circumference, proportion of patients with a history of CVD, and number of hospitalizations were lower than those in the non-PHC group. Furthermore, the PHC group exhibited a significant association with lower hospitalization risk (hazard ratio = 0.825; 95% confidence interval, 0.684 to 0.997; p = 0.046) in the Cox model. Conclusion: This study revealed that PHCs minimized the risk of hospitalization in patients with T2DM. Furthermore, we discussed the effectiveness of PHCs in enhancing health outcomes and reducing health care costs in such patients.

Real-World Efficacy of Glucagon-like Peptide-1 (GLP-1) Receptor Agonist, Dulaglutide, on Metabolic Parameters in Japanese Patients with Type 2 Diabetes: A Retrospective Longitudinal Study.

The glucagon-like peptide-1 receptor agonist (GLP-1RA) dulaglutide has been shown to improve body weight and glycemic control and reduce major cardiovascular (CV) events. In Japan, dulaglutide is used at a fixed dose of 0.75 mg, which is lower than that in Europe and North America. However, the reports of real-world efficacy on metabolic parameters in Japanese patients with type 2 diabetes (T2DM) are limited. This study aimed to examine the real-world efficacy of GLP-1RA dulaglutide on metabolic parameters in Japanese patients with T2DM. We retrospectively selected patients with T2DM who had been prescribed dulaglutide continuously for 12 months or longer between September 2015 and December 2020 and compared metabolic parameters at baseline with the data at 12 months after the start of dulaglutide. One hundred twenty-one patients were enrolled in this study. The 12-month dulaglutide treatment reduced body weight by 1.7 kg and hemoglobin A1c by 1.1%. Significant improvements were also observed in serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and non-HDL-C. The change in HbA1c during dulaglutide treatment was significantly correlated with the changes in HDL-C (R = -0.236, p = 0.013), LDL-C (R = 0.377, p = 0.005) and non-HDL-C (R = 0.415, p < 0.001). The improvements in HbA1c, HDL-C, TG and non-HDL-C were greater in patients concurrently treated with SGLT2 inhibitors (SGLT2is) at baseline. In conclusion, the treatment with dulaglutide has beneficial effects on multiple CV risk factors in Japanese patients with T2DM.