Horii Takeshi

AIMS: Severe hypoglycemia is an important adverse event in type 2 diabetes, particularly among older adults and clinically vulnerable patients. However, recent real-world trends in hypoglycemia requiring hospitalization in Japan are insufficiently characterized. METHODS: We conducted a retrospective cross-sectional study by using Japanese hospital-based claims data for 2009-2022. Patients receiving glucose-lowering medications for type 2 diabetes were included (N = 1,391,948). The primary outcome was hospitalization for hypoglycemia, defined using codes for diagnosis, same-day hospitalization, and intravenous administration of 50% glucose. Secondary outcomes were nocturnal hospitalization and the requirement of emergency transport. Annual frequencies were described, and adjusted risk ratios were estimated using modified Poisson regression analysis. RESULTS: Overall, 7,157 patients were hospitalized for hypoglycemia. The annual frequency decreased from 0.41% in 2009 to 0.21% in 2022; the greatest decline was among patients aged ≥ 75 years, who continued to account for the majority of hospitalizations. An older age and lower body mass index were associated with all hypoglycemia-related outcomes, as were insulin, pioglitazone, glucagon-like peptide-1 receptor agonists, alpha-glucosidase inhibitors, and sulfonylureas. In the sensitivity analysis, impaired kidney function was associated with an increased risk. CONCLUSIONS: Hypoglycemia-related hospitalization declined in Japan during 2009-2022, the residual burden remaining concentrated among older adults.

INTRODUCTION: Lower extremity arterial disease (LEAD) represents a significant atherosclerotic complication in patients with type 2 diabetes (T2D). Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and metformin are commonly prescribed glucose-lowering agents that have demonstrated potential benefits in attenuating atherosclerosis progression. This study examined the impact of SGLT2is and metformin on the risk of developing severe LEAD in elderly patients with T2D. RESEARCH DESIGN AND METHODS: This retrospective cohort study analyzed insurance data for individuals aged 65 years and older with advanced-age health insurance coverage, using health insurance claims and self-reported health check-up data. The observation start date was the initial prescription date of SGLT2is or metformin. Severe LEAD was defined as cases requiring revascularization after a LEAD diagnosis. We conducted a 3-year analysis using propensity score matching to compare the distinct effects of each drug on LEAD risk using a claims database. RESULTS: The final population comprised 31,732 new SGLT2i and metformin users, divided into two groups (n=15,866 patients each). LEAD incidence rates were 2.10 and 2.69 per 1,000 person-years for metformin and SGLT2is, respectively. Compared with metformin, SGLT2is showed a higher HR for severe LEAD, especially in patients with a diastolic blood pressure (dBP) below 80 mm Hg (HR: 2.11; 95% CI: 1.01 to 2.30) and an estimated glomerular filtration rate between 30 and 60 mL/min/1.73 m2 (HR: 2.32; 95% CI: 1.09 to 2.94). CONCLUSION: The endothelial benefits of metformin, achieved without affecting hemodynamics, may be particularly effective in elderly patients with T2D and low dBP or impaired renal function. However, the presence of cardiovascular disease may often lead to the selection of SGLT2is. Nevertheless, prioritizing the use of metformin may be prudent when considering LEAD status.

Diabetic foot lesions are becoming increasingly prevalent due to increases in type 2 diabetes (T2D), aging populations, and atherosclerotic diseases. Individuals with T2D with comorbid lower extremity artery disease (LEAD) are particularly susceptible. Although pharmacological therapies are often combined with risk management strategies, like exercise and smoking cessation, their roles in preventing LEAD progression are unclear. Herein, we investigated factors suppressing LEAD progression in T2D. Using data from the DeSC database, this retrospective cross-sectional study defined severe LEAD as a diagnosis requiring revascularization (Revasc). Logistic regression analysis was used to calculate odds ratios (ORs) for associated factors. The analysis included 243,606 patients with T2D divided into two groups; those with (n = 890) and without (n = 242,716) Revasc. Subgroup analysis of patients with LEAD (n = 27,258) with (n = 890) and without (n = 26,368) Revasc was also conducted. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) (OR 0.50), metformin (OR 0.78), and fibrates (OR 0.75) were associated with a significant reduction in severe LEAD in the primary and subgroup analyses. In conclusion, the active use of SGLT2 inhibitors, metformin, and fibrates may help prevent LEAD progression. However, these medications are associated with adverse events, making it essential to manage patients individually to optimize benefits while minimizing risks.