Horii Takeshi

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.

Adherence and treatment continuation rates of the glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide for both oral (O-SEMA) and subcutaneous injection (SEMA-SC) remain unknown in real-world clinical practice. This retrospective observational study compared the 12 month adherence and treatment discontinuation of O-SEMA and once-weekly SEMA-SC in patients with type 2 diabetes using a real-world claims database. SEMA-SC initiators were 1:1 propensity score-matched to O-SEMA initiators. Non-adherence was defined as <0.8 of the proportion of days covered. SEMA-SC had a significantly higher odds ratio (OR) for non-adherence than O-SEMA (OR: 1.39). The hazard ratio for treatment discontinuation, using O-SEMA as the reference, was 1.45 for SEMA-SC, although the discontinuation rate of O-SEMA was higher during the early stage. O-SEMA initiators showed significantly higher adherence and greater persistence in therapy than SEMA-SC initiators at 12 months, which could lead to earlier initiation of GLP-1RA treatment.