Of the three separate cohorts examined in this study, the results presented focus on the 2020 study cohort as the most recent data. Of 168,995 patients with T2D who had a health checkup in 2020, 157,547 were prescribed a hypoglycemic drug during 2020. Following the exclusion criteria, a total of 155,653 patients were included in the 2020 study cohort (Fig. 2).

Patient selection for the 2020 study cohort. Diagnosis of T2D was based on ICD-10 codes E11 (type 2 diabetes mellitus), E12 (malnutrition-related diabetes mellitus), E13 (other specified diabetes mellitus), and E14 (unspecified diabetes mellitus). ATC Anatomical Therapeutic Chemical, ICD-10 International Classification of Diseases-10th revision, T2D type 2 diabetes

Overall, the majority of patients were men (81.6%; Supplementary Materials Fig. S1) with a mean age of 54.6 ± 8.5 years (Table 1). Patient characteristics were largely similar across the study cohorts (Supplementary Materials Table S2), including the relative proportions of men and women (Supplementary Materials Fig. S1). The mean BMI of the cohort was 26.9 ± 4.9 kg/m2, with 38.1%, 39.4%, and 22.5% of patients in the BMI < 25 kg/m2, 25 to < 30 kg/m2, and ≥ 30 kg/m2 subgroups, respectively. Mean waist circumference of the cohort was 92.4 ± 11.9 cm (men 92.8 cm; women 90.5 cm). Patients with metabolic syndrome had a higher mean BMI and waist circumference (BMI 29.1 ± 4.5 kg/m2; waist circumference 98.3 ± 10.0 cm) compared with patients without metabolic syndrome (BMI 25.2 ± 4.5 kg/m2; waist circumference 87.9 ± 11.2 cm), as well as higher blood pressure, low-density lipoprotein cholesterol and triglyceride levels, fasting blood glucose levels, and HbA1c (Table 1).

Patients with T2D had similar rates of comorbidities regardless of whether they also had metabolic syndrome; however, those with metabolic syndrome had higher rates of antihypertensive drug use (42.1% versus 31.5%, respectively) and lipid-lowering drug use (55.9% versus 52.9%, respectively) compared with patients without metabolic syndrome (Table 1).

Overall, the prevalence of metabolic syndrome was 43.0% (95% confidence interval [CI] 42.7, 43.2) in Japanese patients with T2D, which remained largely unchanged between 2018 and 2020 (Supplementary Materials Fig. S2). The prevalence of metabolic syndrome was 17.3% in the BMI < 25 kg/m2 subgroup, increasing to 54.6%, and 66.1%, respectively, in the BMI 25 to < 30 kg/m2 and BMI ≥ 30 kg/m2 subgroups (Fig. 3). In each BMI subgroup, men had a higher prevalence of metabolic syndrome compared to women (overall prevalence 46.6% versus 27.0%), with prevalence increased in both men and women subgroups at higher BMI (men versus women: BMI < 25 kg/m2, 20.6% versus 3.4%; BMI 25 to < 30 kg/m2, 58.8% versus 32.6%; BMI ≥ 30 kg/m2, 68.6% versus 56.3%; Fig. 3).

Trends in the prevalence of metabolic syndrome by sex and BMI subgroups in the 2020 study cohort. BMI body mass index

The sensitivity analysis using a modified definition of metabolic syndrome (Fig. 1b) showed a prevalence of 57.2% (95% CI 57.0, 57.5) in Japanese patients with T2D, with trends similar to the main analysis when examined by sex (men versus women 61.5% versus 38.5%; Supplementary Materials Fig. S3).

In the higher BMI subgroups, patients with T2D and metabolic syndrome had higher rates of comorbidity compared to those in the lowest BMI (< 25 kg/m2) subgroup (Fig. 4). The most common comorbidities in all BMI subgroups were congestive heart failure (BMI < 25 kg/m2, 1.4%; BMI 25 to < 30 kg/m2, 4.8%; BMI ≥ 30 kg/m2, 6.8%) and chronic kidney disease (BMI < 25 kg/m2, 2.0%; BMI 25 to < 30 kg/m2, 6.2%; BMI ≥ 30 kg/m2, 6.5%). Similarly, the proportion of patients with T2D and metabolic syndrome who were prescribed cardiovascular medications was higher in patients with BMI ≥ 25 kg/m2 compared to those with BMI < 25 kg/m2 (Fig. 5), including antihypertensive drugs (BMI < 25 kg/m2, 6.4%; BMI 25 to < 30 kg/m2, 22.1%; BMI ≥ 30 kg/m2, 30.8%), lipid-lowering drugs (BMI < 25 kg/m2, 9.0%; BMI 25 to < 30 kg/m2, 31.1%; BMI ≥ 30 kg/m2, 37.0%), and aspirin (BMI < 25 kg/m2, 1.3%; BMI 25 to < 30 kg/m2, 3.8%; BMI ≥ 30 kg/m2, 3.5%).

Trends of comorbidities in patients with T2D and metabolic syndrome by BMI subgroups in the 2020 study cohort. Proportion of patients in each BMI subgroup with a congestive heart failure; b stroke (ischemic and hemorrhagic); c CKD; d myocardial infarction; and e atrial fibrillation. BMI body mass index, CKD chronic kidney disease, T2D type 2 diabetes

Use of cardiovascular medications in patients with T2D and metabolic syndrome by BMI subgroups in the 2020 study cohort. Proportion of patients prescribed a lipid-lowering drugs; b antihypertensive drugs; and c aspirin. BMI body mass index, T2D type 2 diabetes