堀井 剛史

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.

AIMS: This study aimed to investigate the factors associated with the exacerbation of the severity of atherothrombotic brain infarction at discharge in patients with type 2 diabetes using a large-scale claims database. MATERIALS AND METHODS: This retrospective cross-sectional study utilized the Medical Data Vision administrative claims database, a nationwide database in Japan using acute care hospital data, and the Diagnosis Procedure Combination system. Diagnosis Procedure Combination data collected between April 1, 2008, and December 31, 2022, were extracted. Patients with type 2 diabetes were included. Severe atherothrombotic brain infarction was defined as a modified Rankin scale score of ≥3. RESULTS: Severe atherothrombotic brain infarction occurred in 43,916/99,864 (44.0%) patients with type 2 diabetes. The odds ratio for severe atherothrombotic brain infarction increased significantly per 10 year increments in age (odds ratio: 1.69, 95% confidence interval: 1.66-1.71). A body mass index of <25 kg/m2, with a body mass index of ≥25 kg/m2 as reference, also increased the risk for severe atherothrombotic brain infarction (odds ratio: 1.11, 95% confidence interval: 1.08-1.15). The odds ratios in insulin and dipeptidyl peptidase 4 inhibitor use were significantly higher than 1. In particular, statin use (odds ratio: 0.85, 95% confidence interval: 0.83-0.88), fibrate use (odds ratio: 0.68, 95% confidence interval: 0.59-0.78), aspirin use (odds ratio: 0.78, 95% confidence interval: 0.75-0.80), and P2Y12 inhibitor use (odds ratio: 0.88, 95% confidence interval: 0.85-0.91) were associated with a lower odds ratio for severe atherothrombotic brain infarction. CONCLUSIONS: The active management of lipid levels using statins and fibrates may be beneficial in preventing the exacerbation of atherothrombotic brain infarction in type 2 diabetes patients.

BACKGROUND: Anamorelin is the first drug approved for the treatment of cancer cachexia, a debilitating condition characterized by weight loss, anorexia, and muscle mass depletion. Cachexia negatively affects a patient's quality of life, survival, and response to chemotherapy. Studies describing anamorelin use are currently limited to a small number of pancreatic cancer cases. OBJECTIVES: We aimed to examine the incidence and risk factors of adverse metabolic effects on glucose levels in cachexia patients with various carcinomas treated with anamorelin. METHOD: We used real-world data of patients who received anamorelin between August 2021 and July 2022 and were registered in the JMDC claims database. We investigated the impact of metabolic adverse effects on glucose in patients receiving anamorelin with respect to the following factors: sex (male), age (>75 years), types of carcinoma, history of diabetes mellitus (DM), and concomitant use of steroids. RESULTS: The incidence of adverse metabolic effects on glucose was 12.3%, and pancreatic cancer and history of DM were associated with adverse metabolic effects on glucose. The median onset of adverse metabolic effects on glucose was 17 days after anamorelin treatment. CONCLUSIONS: This study highlights the need to monitor and manage hyperglycemia in cachexia patients receiving anamorelin, especially in those with pancreatic cancer and a history of DM.

We aimed to compare the effects of cardiovascular disease risk in Japanese patients with type 2 diabetes on sodium-glucose cotransporter 2 inhibitors (SGLT2Is) or metformin. This retrospective, real-world cohort study was carried out using a claims database and propensity score matching; 58,402 eligible patients (29,201 per group) were included. The outcomes included nonfatal myocardial infarction, angina pectoris, nonfatal stroke, hospitalization for heart failure and composite end-points. The hazard ratio (HR) for the composite end-point was 0.79, which was lower for SGLT2Is than for metformin. For male patients (HR 0.76), patients aged <65 years (HR 0.94), patients aged ≥75 years (HR 0.78) and patients with body mass index ≥25 kg/m2 (HR 0.76), the HRs for the composite end-point were significantly lower in the SGLT2I group than in the metformin group. SGLT2Is might be superior to metformin in reducing the composite risk of cardiovascular disease in patients with type 2 diabetes.

INTRODUCTION: Hypoglycemia is listed as an adverse effect in the package inserts of not only hypoglycemic agents but also many other drugs. We aimed to clarify real-world factors related to an increased risk of hypoglycemia-related hospitalization (HRH) in Japanese patients with type 2 diabetes (T2D) on non-hypoglycemic agents that have been associated with hypoglycemia. RESEARCH DESIGN AND METHODS: This cross-sectional study was performed using data from the Medical Data Vision administrative claims database. We identified patients with T2D who were enrolled in the database between April 2014 and October 2019. Logistic regression analyses were performed to identify clinical factors associated with HRH due to non-hypoglycemic agents. RESULTS: Among 703 745 patients with T2D, 10 376 patients (1.47%) experienced HRH. The use of 332 non-hypoglycemic agents was associated with hypoglycemia. Multivariate analysis was performed to calculate OR for HRH. Seventy-five drugs had an OR greater than 1, and the values were significant. The OR was the highest for diazoxide (OR 15.5, 95% CI 4.87 to 49.3). The OR was higher than 2.0 for methylphenidate (OR 5.15, 95% CI 1.53 to 17.3), disulfiram (OR 4.21, 95% CI 2.05 to 8.62) and hydrocortisone (OR 2.89, 95% CI 1.11 to 7.51). CONCLUSION: This large retrospective analysis revealed that the risk of HRH from some non-hypoglycemic agents in patients with T2D may be increased. The results of this study are expected to support treatment planning by physicians and healthcare professionals involved in diabetes care.

BACKGROUND: We aimed to clarify the relationship between coronavirus disease 2019 (COVID-19) reinfection and basic disease and smoking status. METHODS: The electronic health records of 165,320 patients with COVID-19 from January 1, 2020, to August 27, 2021, were analyzed. Data on age, race, sex, smoking status (never, current, former), and basic disease were analyzed using Cox proportional hazard models. RESULTS: In total, 6,133 patients (3.7%) were reinfected. The overall reinfection rate for never, current, and former smokers was 4.2, 3.5, and 5.7%, respectively. Although the risk of reinfection was highest among former smokers aged ≥65 years (7.7% [422/5,460]), the reinfection rate among current smokers aged ≥65 years was 6.2% (341/5,543). Among reinfected patients, the number of basic diseases was higher in former smokers (2.41 ± 1.16) than in current (2.28 ± 1.07, P = 0.07) and never smokers (2.07 ± 1.05, P < 0.001). Former smokers who are older may have been exposed to factors that increase their risk of symptomatic COVID-19 reinfection.

<title>Abstract</title><sec> <title>Objective</title> In the diabetes treatment policy after the Kumamoto Declaration 2013, it is difficult to accurately predict the incidence of complications in patients using the JJ risk engine. This study was conducted to develop a prediction equation suitable for the current diabetes treatment policy using patient data from Kitasato University Kitasato Institute Hospital (Hospital A) and to externally validate the developed equation using patient data from Kitasato University Hospital (Hospital B). Outlier tests were performed on the patient data from Hospital A to exclude the outliers. Prediction equation was developed using the patient data excluding the outliers and was subjected to external validation. </sec><sec> <title>Results</title> By excluding outlier data, we could develop a new prediction equation for the incidence of coronary heart disease (CHD) as a complication of type 2 diabetes, incorporating the use of antidiabetic drugs with a high risk of hypoglycemia. This is the first prediction equation in Japan that incorporates the use of antidiabetic drugs. We believe that it will be useful in preventive medicine for treatment for people at high risk of CHD as a complication of diabetes or other diseases. In the future, we would like to confirm the accuracy of this equation at other facilities. </sec>

The impact of overlapping risk factors on coronavirus disease (COVID-19) severity is unclear. To evaluate the impact of type 2 diabetes (T2D) and obesity on COVID-19 severity, we conducted a cohort study with 28,095 anonymized COVID-19 patients using data from the COVID-19 Research Database from January 1, 2020 to November 30, 2020. The mean age was 50.8 ± 17.5 years, and 11,802 (42%) patients were male. Data on age, race, sex, T2D complications, antidiabetic medication prescription, and body mass index ≥ 30 kg/m2 (obesity) were analysed using Cox proportional hazard models, with hospitalization risk and critical care within 30 days of COVID-19 diagnosis as the main outcomes. The risk scores were 0-4 for age ≥ 65 years, male sex, T2D, and obesity. Among the participants, 11,294 (61.9%) had obesity, and 4445 (15.8%) had T2D. T2D, obesity, and male sex were significantly associated with COVID-19 hospitalization risk. Regarding hospitalization risk scores, compared with those for hospitalization risk score 0 and critical care risk score 0, hazard ratios [95% confidence intervals] were 19.034 [10.470-34.600] and 55.803 [12.761-244.015] (P < 0.001) (P < 0.001), respectively, for risk score 4. Complications from diabetes and obesity increased hospitalization and critical care risks for COVID-19 patients.

AIMS/INTRODUCTION: This study aimed to investigate the risk of diabetic ketoacidosis (DKA) in insulin-treated type 1 diabetes (T1D) patients administered Sodium-glucose cotransporter 2 (SGLT2) inhibitors in real-world clinical practice. MATERIALS AND METHODS: We conducted a real-world, retrospective, observational cohort study using Japanese Medical Data Vision, a diagnosis procedure combination database. We identified insulin-treated adult T1D patients enrolled from December 2018 to October 2019. We assessed the incidence and risk of DKA in T1D patients using SGLT2 inhibitors in an "on-label" manner. Cox multivariate regression analyses were performed to determine clinical factors linked to SGLT2 inhibitor-associated DKA. RESULTS: Of 11,475 T1D patients, 1,898 (16.5%) were prescribed SGLT2 inhibitors. DKA occurred in 139 (7.3%) of these patients, with 20.2 incidences per 100 person-years. These patients also showed significantly higher DKA rates than did those not receiving SGLT2 inhibitors (hazard ratio, 1.66; 95% CI, 1.33-2.06; p <0.001). The mean time until DKA onset in SGLT2 inhibitor-treated T1D patients was 30.6 (±30.1) days. The risk of SGLT2 inhibitor-associated DKA increased in T1D patients irrespective of sex, age, or body mass index (BMI). However, the risk did not increase in T1D patients receiving continuous subcutaneous insulin infusion (CSII), which warrants further investigation because of the small number of T1D patients receiving CSII. CONCLUSIONS: "On-label" SGLT2 inhibitor use may increase DKA risk among insulin-treated T1D patients irrespective of sex, age, or BMI. Both T1D patients and healthcare providers should be wary of DKA, especially during the first month of initiating SGLT2 inhibitors.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are believed to lower glucose levels and inhibit cardiovascular events related to type 2 diabetes (T2D). To maximize their benefits, the risk of resultant hypoglycemia has to be minimized; however, the magnitude of this risk remains unclear. Here, we aimed to identify clinical factors linked to an increased risk of hypoglycemia among Japanese patients with T2D and treated with SGLT2 inhibitors. RESEARCH DESIGN AND METHODS: This was a real-world retrospective cohort study conducted using the Japanese Medical Data Vision database. We identified patients with T2D and treated with SGLT2 inhibitors who were enrolled in the database from April 2014 to October 2019. Cox multivariate regression analyses were performed to determine demographical and clinical factors linked to SGLT2 inhibitor-associated hypoglycemia-related hospitalization. RESULTS: Of 171 622 patients prescribed SGLT2 inhibitors, hypoglycemia-related hospitalization occurred in 216 (0.13%), with 0.60 incidences per 100 person-years. The risk of SGLT2 inhibitor-associated hypoglycemia was higher with each 10-year increase in age (HR 1.49; 95% CI 1.32 to 1.68) and high in patients with body mass index <25 kg/m2 (HR 1.98; 95% CI 1.50 to 2.61), insulin use (HR 3.26; 95% CI 2.43 to 4.38), and sulfonylurea use (HR 1.44; 95% CI 1.02 to 2.03). The risk was lower in women than in men (HR 0.73; 95% CI 0.54 to 0.98) and low in concomitant metformin users (HR 0.52; 95% CI 0.37 to 0.74). CONCLUSIONS: These findings may help minimize the risk of hypoglycemia-related hospitalization due to T2D treatment with SGLT2 inhibitors. We revealed that the risk of hypoglycemia may be higher when combining SGLT2 inhibitors with sulfonylureas and/or insulin. Furthermore, we discovered a high risk of hypoglycemia in older and non-obese patients. These findings may assist in maximizing the benefits of SGLT2 inhibitors for the treatment of T2D.

OBJECTIVE: Investigation of polypharmacy in patients with type 2 diabetes revealed that medications administered according to the patient's symptoms and complaints strongly contributed to polypharmacy. We explored the effects of clinical ward pharmacy service, which evaluated the need for symptomatic treatment, therefore minimizing polypharmacy by reducing inappropriate medications. RESULTS: The number of drugs (hospitalization vs. discharge: 9 [1-17] vs. 7 [1-16], P < 0.001) and rate of polypharmacy (hospitalization vs. discharge: 75.4% vs. 61.1%, P < 0.001) were significantly lower at discharge. Since hospital admission, the number of drugs increased (n = 6, 11%), remained unchanged (n = 15, 28%), decreased by 1 drug (n = 4, 8%), decreased by 2 drugs (n = 3, 6%), and decreased by more than 2 drugs (n = 25, 47%). Daily drug costs were significantly reduced (hospitalization vs. discharge: $8.3 vs. $6.1, P < 0.001).

2型糖尿病に対する第一選択薬として処方頻度の増加しているDipeptidyl peptidase-4（DPP-4）阻害薬であるシタグリプチン（以下，Sita）もしくはメトホルミン（以下，Met）による治療開始後の治療強化の必要性と，血糖コントロールへの影響について検討を行った．対象はMet 587例，Sita 177例で，HbA1cはベースラインに差はなく，24，48，72，96週でSitaが有意に低かった．96週のHbA1c<7.0％達成についてMetをReferenceとしSitaで調整オッズ比1.70（95％ CI: 1.18–2.46）と有意な値を示し，第一選択薬による単剤での治療期間について，MetをReferenceとしたSitaの調整Coxハザード比は0.61（95％ CI: 0.50–0.76），log-rank検定のいずれにおいても有意な値を示した．以上より2型糖尿病患者に対するSitaを第一選択とした薬物療法を開始した結果，Metと比較し良好な血糖コントロールを保ち，より長期において強化を伴わない治療の継続が可能であると考えられた．

ピオグリタゾンに対する膀胱がん発症リスクを検討する臨床試験の結果を受け，ピオグリタゾンを中止，もしくは作用機序の異なるDPP-4阻害薬であるシタグリプチンへの変更が散見された．そこで，ピオグリタゾンが継続となった患者（以下，継続群）とピオグリタゾンを中止し他の経口血糖降下薬を新たに投与されなかった患者（以下，変更薬なし群），ピオグリタゾンをシタグリプチンへ変更した患者（以下，シタグリプチン群）におけるHbA1c, AST, ALT, HDL-Cへの影響をレトロスペクティブに分析した．変更薬なし群ではHbA1c, AST, ALTが上昇，HDL-Cが低下を示した．シタグリプチン群で男性およびBMI25未満の症例で血糖降下作用が効果的に表れていることが推測でき，女性およびBMI25以上の症例ではHbA1cが上昇する傾向にあった．AST, ALTが上昇，HDL-Cが低下を示したことから，膵外作用の変動に注目する必要性が考えられた．HbA1cに対する影響はシタグリプチンへ変更で有意に低く，BMI高値が有意に高いことが示唆された．ピオグリタゾンからシタグリプチンへ変更を行うことでHbA1cのみならず膵外作用への影響について留意する必要性があり，特にピオグリタゾンの感受性が高い女性やBMI高値の症例において，留意する必要性が考えられる．