Age-wise examination of the association of obesity based on body mass index and waist circumference with metabolic diseases in comprehensive health checkup participants.

Aim: Body mass index and waist circumference are used for obesity diagnosis and screening of visceral fat; however, their evidence in older adults is insufficient. This study investigated the age-specific association of body mass index and waist circumference with metabolic diseases, assessing their applicability as diagnostic criteria for individuals aged ≥65 years. Methods: Analysis included 46,324 individuals aged ≥18 years, categorized into five age groups: 18-44, 45-54, 55-64, 65-74, and ≥75 years. Logistic regression analyses identified associations between obesity and metabolic diseases, stratified by age and sex. Results: Men with obesity based on body mass index had a significantly high risk of hypertension, diabetes mellitus, and dyslipidemia across all age groups (all, p < 0.05). Obesity based on waist circumference was significantly positively associated with all metabolic diseases (all, p < 0.05). Women with obesity based on body mass index and waist circumference had a significantly high risk of all metabolic diseases across all age groups (all, p < 0.05), except for diabetes mellitus in individuals aged ≥75 years. Conclusions: Participants with obesity based on body mass index and waist circumference exhibited a high risk of hypertension, diabetes mellitus, and dyslipidemia among those aged 18-74 years and men aged ≥75 years. This study contributes to the early prevention and control of metabolic diseases.

Real-world use of glucagon-like peptide-1 receptor agonists in Japanese patients with type 2 diabetes: A retrospective database study (DEFINE-G).

AIMS: To understand glucagon-like peptide-1 receptor agonist (GLP-1RA) use in patients with type 2 diabetes (T2D) in Japan. METHODS: Characteristics of people receiving GLP-1RAs between 2016 and 2020 in the J-DREAMS database were investigated. Changes in HbA1c, body weight (BW), body mass index (BMI), and proportion reaching HbA1c targets were analysed in GLP-1RA-naïve patients 6-24 months after GLP-1RA initiation. RESULTS: The proportion of patients with GLP-1RA prescriptions increased from 3.6% to 9.6% during 2016-2020. Among GLP-1RA-naïve patients (n = 569), HbA1c reduced -|0.6% (95% confidence interval [CI] -0.7, -0.5; -6 mmol/mol [95% CI -7, -5]) 6 months after treatment initiation and stabilised until 24 months (P < 0.001); mean BW and BMI reduced -1.05 kg (95% CI -1.31, -0.80) and -0.43 kg/m2 (95% CI -0.53, -0.32), respectively, at 6 months (P < 0.001). The proportion of GLP-1RA-naïve patients with HbA1c < 7.0% (<53 mmol/mol) and <8.0% (<64 mmol/mol) increased from 16% to 27% and 43% to 65%, respectively, and an HbA1c reduction of ≥1.0% (≥11 mmol/mol) was observed in 33% of patients after 6 months (P < 0.001). CONCLUSIONS: This study shows increased GLP-1RA prescriptions over 5 years. HbA1c and BW reduced 6 months after GLP-1RA initiation in patients with T2D in a Japanese real-world setting.

Long-Term Safety and Clinical Outcomes with Insulin Degludec/Insulin Aspart Treatment in Japanese Patients with Diabetes: A Real-World, Prospective, Observational Study.

INTRODUCTION: Insulin degludec/insulin aspart (IDegAsp) provides effective glycaemic control with an acceptable safety profile in Japanese patients with diabetes in randomised clinical trials. This post-marketing surveillance study assessed long-term safety and clinical outcomes with IDegAsp in a Japanese real-world setting. METHODS: Multicentre, prospective, observational, open-label, single-arm study of Japanese patients with diabetes requiring insulin therapy, who had switched to IDegAsp at their treating physician's discretion in clinical practice. One year after initiating IDegAsp, incidence of adverse events (AEs [primary endpoint]), serious AEs, adverse drug reactions (ADRs), and severe hypoglycaemia (secondary safety endpoints) were assessed in the safety analysis set (SAS). Secondary effectiveness endpoints were change from baseline in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) in the effectiveness analysis set (EAS). RESULTS: Overall, 1321 patients were included (SAS, n = 1321; EAS, n = 1285); 4.2% with type 1 diabetes, 95.2% with type 2 diabetes, 0.7% with other/unknown diabetes type. In total, 204 AEs were reported in 132 patients (10.0% of the SAS), at a rate [95% confidence interval (CI)] of 16.2 events/100 patient-years of exposure (PYE) [14.0; 18.4]. By preferred term, 'hypoglycaemia' was the most frequent AE (45 events in 31 patients [2.3%]; rate [95% CI] 3.6 events/100 PYE [2.5; 4.6]). Serious AEs occurred in 4.2% of patients (rate [95% CI] 5.7 events/100 PYE [4.4; 7.0]), and ADRs in 3.1% (rate [95% CI] 4.6 reactions/100 PYE [3.4; 5.8]). Six events of severe hypoglycaemia were reported in five patients (0.4%; rate [95% CI] 0.5 events/100 PYE [0.1; 0.9]). Change from baseline to 1 year was - 0.51% and - 32.1 mg/dL for HbA1c and FPG, respectively (P < 0.0001 for both). CONCLUSION: In Japanese patients with diabetes, initiation of IDegAsp in real-world clinical practice was well tolerated, with no new safety signals, and associated with improved glycaemic control after 1 year. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02821052.

A Real-World, Prospective, Non-interventional Study of Adults with T2D Switching to IDegAsp from Glargine U100 or U300 in Japan.

INTRODUCTION: This real-world study investigated glycaemic control and quality of life (QoL) in insulin-experienced Japanese patients with type 2 diabetes (T2D) who switched to insulin degludec/insulin aspart (IDegAsp). METHODS: This was a prospective, non-interventional, open-label, single-arm study. Eligible patients were adults (aged ≥ 20 years) with T2D, previously treated with insulin glargine 100 or 300 units/mL (glargine U100/U300) with or without prandial insulin, who switched to IDegAsp as part of routine practice. Change from baseline to end of study (EOS; 26 weeks after initiation or IDegAsp discontinuation) in the following endpoints was assessed by adjusted mixed models for repeated measures: glycated haemoglobin (HbA1c; primary endpoint), fasting plasma glucose (FPG), insulin dose and total Diabetes Therapy-Related Quality of Life (DTR-QoL) score. Non-severe hypoglycaemia was assessed in the 4-week period prior to initiating IDegAsp and in the 4-week period before EOS or discontinuation using negative binomial regression. RESULTS: The full analysis set included 236 patients from 29 centres in Japan with mean (± SD) age 63.2 years (± 12.3), HbA1c 7.7% (± 1.0) and diabetes duration 14.9 (± 9.3) years. After 26 weeks with IDegAsp, HbA1c (estimated change - 0.1% [- 0.2; 0.0]95% confidence interval (CI), p = 0.3036) and FPG (- 7.5 mg/dL [- 23.5; 8.5]95% CI, p = 0.3477) were maintained; there were significant reductions in basal and total insulin dose: estimated change of - 3.4 units/day [- 3.8; - 3.0]95% CI and - 1.0 units/day [- 1.9; - 0.1]95% CI, respectively (both p < 0.05). Non-severe hypoglycaemia rates were similar in the periods before and after initiating IDegAsp, while there was a significant improvement in total DTR-QoL score after 26 weeks with IDegAsp (p = 0.0012). CONCLUSION: These real-world data suggest that switching to IDegAsp from glargine U100 or U300 was well tolerated in a Japanese population with T2D, with no new safety or tolerability signals, and associated with maintenance of glycaemic control and improved QoL. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov: NCT03745157.

A Japanese Study Assessing Glycemic Control with Use of IDegAsp Co-formulation in Patients with Type 2 Diabetes in Clinical Practice: The JAGUAR Study.

INTRODUCTION: The aim of this study was to evaluate the glycemic control and safety of insulin degludec/insulin aspart (IDegAsp) co-formulation in Japanese patients with type 2 diabetes (T2D) in a real-world clinical setting, including elderly patients (aged > 75 years). METHODS: Patients (≥ 18 years) diagnosed with T2D, previously treated with insulin were included from the Japanese Medical Data Vision database. Baseline data were taken at the index date, defined as the first IDegAsp prescription claim. Change in glycated hemoglobin (HbA1c) at 12 months was estimated using a mixed model repeated measures analysis. The proportion of patients achieving target HbA1c < 8.0% without experiencing hypoglycemia (identified by International Classification of Disease codes) was calculated at 12 months (365 ± 90 days) after baseline. RESULTS: Overall, 10,798 patients were included, 3940 were aged > 75 years, and 913 had baseline HbA1c values available. Switching to IDegAsp was associated with significantly improved HbA1c values at 12 months (- 1.23% [- 1.43, - 1.02]95%CI, p < 0.001) versus baseline. Moreover, relative to baseline, a significantly greater proportion of patients achieved HbA1c < 8.0% without hypoglycemia at 12 months, relative rate (RR) 1.30 [1.15, 1.45]95%CI, p < 0.001. Results were similar for patients aged ≤ 75 years and aged > 75 years; 66% and 64% of patients, respectively, achieved HbA1c < 8.0% without hypoglycemia at 12 months. CONCLUSION: Switching from insulin to IDegAsp co-formulation was associated with significantly improved glycemic control and a reduction in hypoglycemia rate during 12 months of follow-up in Japanese patients with T2D, including those aged > 75 years.

Clinical considerations for use of insulin degludec/insulin aspart in Japanese patients.

INTRODUCTION: Co-formulation of basal and bolus insulin components provides a simpler regimen for patients with type 2 diabetes than separate basal-bolus treatment. However, conventional premixed insulin products include a suboptimal protaminated basal component that requires resuspension prior to injection. Insulin degludec/insulin aspart (IDegAsp) is the first soluble co-formulation of a basal insulin with an ultra-long duration of action (IDeg) and a rapid-acting bolus insulin (IAsp) in a single injection. AREAS COVERED: In this review, the authors summarize findings from pre-clinical studies and the clinical trial program and provide guidance for the initiating and switching of IDegAsp in different patient populations. Pharmacodynamic analyses have revealed a rapid onset of action and distinct peak (IAsp), followed by a separate, flat and stable basal effect (IDeg component). Phase 3 studies have demonstrated the efficacy and safety of IDegAsp, with greater glycemic improvements than basal-only therapy in international and Japanese type 2 diabetes populations. IDegAsp also results in reduced insulin dose requirements and lower rates of hypoglycemia than premixed insulin. EXPERT OPINION: IDegAsp provides a simple and effective insulin regimen in appropriately selected Japanese patients, with the flexibility to suit individual needs. The benefits of IDegAsp over conventional insulin regimens might help tackle clinical inertia with insulin intensification.