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.

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.

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.