Aims To examine the manifestation of cardiovascular or renal disease (CVRD) in patients with type 2 diabetes (T2D) initially free from CVRD as well as the mortality risks associated with these diseases. Methods Patients free from CVRD were identified from healthcare records in England, Germany, Japan, the Netherlands, Norway and Sweden at a fixed date. CVRD manifestation was defined by first diagnosis of cardiorenal disease, or a stroke, myocardial infarction (MI) or peripheral artery disease (PAD) event. The mortality risk associated with single CVRD history of heart failure (HF), chronic kidney disease (CKD), MI, stroke or PAD was compared with that associated with CVRD‐free status. Results Of 1 177 896 patients with T2D, 772 336 (66%) were CVRD‐free and followed for a mean of 4.5 years. A total of 137 081 patients (18%) developed a first CVRD manifestation, represented by CKD (36%), HF (24%), stroke (16%), MI (14%) and PAD (10%). HF or CKD was associated with increased cardiovascular and all‐cause mortality risk: hazard ratio (HR) 2.02 (95% confidence interval [CI] 1.75–2.33) and HR 2.05 (95% CI 1.82–2.32), respectively. HF and CKD were separately associated with significantly increased mortality risks, and the combination was associated with the highest cardiovascular and all‐cause mortality risk: HRs 3.91 (95% CI 3.02–5.07) and 3.14 (95% CI 2.90–3.40), respectively. Conclusion In a large multinational study of >750 000 CVRD‐free patients with T2D, HF and CKD were consistently the most frequent first cardiovascular disease manifestations and were also associated with increased mortality risks. These novel findings show these cardiorenal diseases to be important and serious complications requiring improved preventive strategies.

Introduction: An abnormal serum potassium (S-K) level is an important electrolyte disturbance. However, its relation to clinical outcomes in real-world patients, particularly hyperkalemia burden, is not extensively studied. Methods: An observational retrospective cohort study using a Japanese hospital claims database was done (April 2008-September 2017; N ¼ 1,022,087). Associations between index S-K level and 3-year survival were modeled using cubic spline regression. Cox regression model was applied to estimate the time to death according to different S-K levels. Prevalence, patient characteristics, treatment patterns, and management of patients with hyperkalemia from first episode were assessed. Results: Hyperkalemia prevalence was 67.9 (95% confidence interval [CI]: 67.1-68.8) per 1000 and increased in patients with chronic kidney disease (CKD) (227.9; 95% CI: 224.3-231.5), heart failure (134.0; 95% CI: 131.2-136.8), and renin-angiotensin-aldosterone system inhibitor (RAASi) use (142.2; 95% CI: 139.6-144.7). U-shaped associations between S-K level and 3-year survival were observed with nadir 4.0 mEq/l. The risk of death was increased at S-K 5.1-5.4 mEq with hazard ratio of 7.6 (95% CI: 7.2-8.0). The 3year mortality rate in patients with CKD stages 3a, 3b, 4, and 5 with normokalemia were 1.51%, 3.93%, 10.86%, and 12.09%, whereas that in patients with CKD stage 3a at S-K 5.1-5.4, 5.5-5.9, and $6.0 mEq/l increased to 10.31%, 11.43%, and 22.64%, respectively. Despite treatment with loop diuretics (18.5%) and potassium binders (5.8%), >30% of patients had persistently high S-K ($5.1 mEq/l). Conclusion: This study provides real-world insight on hyperkalemia based on a large number of patients with various medical backgrounds.

Aims We compared the new use of sodium‐glucose cotransporter‐2 inhibitor (SGLT2i) versus dipeptidyl peptidase‐4 inhibitor (DPP4i) and the risk of cardiorenal disease, heart failure (HF) or chronic kidney disease (CKD), in patients with type 2 diabetes without a history of prevalent cardiovascular and renal disease, defined as cardiovascular and renal disease (CVRD) free, managed in routine clinical practice. Materials and methods In this observational cohort study, patients were identified from electronic health records from England, Germany, Japan, Norway, South Korea and Sweden, during 2012‐2018. In total, 1 006 577 CVRD‐free new users of SGLT2i or DPP4i were propensity score matched 1:1. Unadjusted Cox regression was used to estimate hazard ratios (HRs) for outcomes: cardiorenal disease, HF, CKD, stroke, myocardial infarction (MI), cardiovascular and all‐cause mortality. Results Baseline characteristics were well balanced between the treatment groups (n = 105 130 in each group) with total follow‐up of 187 955 patient years. Patients had a mean age of 56 years, 43% were women and they were indexed between 2013 and 2018. The most commonly used agents were dapagliflozin (91.7% of exposure time) and sitagliptin/linagliptin (55.0%), in the SGLT2i and DPP4i, groups, respectively. SGLT2i was associated with lower risk of cardiorenal disease, HF, CKD, all‐cause and cardiovascular mortality; HR (95% confidence interval), 0.56 (0.42‐0.74), 0.71 (0.59‐0.86), 0.44 (0.28‐0.69), 0.67 (0.59‐0.77), and 0.61 (0.44‐0.85), respectively. No differences were observed for stroke [0.87 (0.69‐1.09)] and MI [0.94 (0.80‐1.11)]. Conclusion In this multinational observational study, SGLT2i was associated with a lower risk of HF and CKD versus DPP4i in patients with type 2 diabetes otherwise free from both cardiovascular and renal disease.

Aims To examine heart failure (HF) and chronic kidney disease (CKD) risks reduction associated with sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2i) compared to other glucose‐lowering drugs (oGLD) in the early stage of type 2 diabetes patients without established cardiovascular or renal diseases (CVRD‐free T2D). Materials and Methods We performed an observational cohort study using a Japanese hospital claims registry, Medical Data Vision. CVRD‐free T2D patients were identified between 1 April 2014 and 30 September 2018. SGLT‐2i and oGLD new users (and dipeptidyl peptidase 4 inhibitors [DPP‐4i] separately) were subjected to 1:1 propensity‐score matching analysis. Hazard ratios (HRs) of cardiorenal disease (HF and/or CKD), HF, CKD, stroke, myocardial infarction (MI), and all‐cause mortality, were estimated using unadjusted Cox regression. Results A total of 108 362 CVRD‐free patients including 54 181 SGLT‐2i and 54 181 oGLD users were matched. Baseline characteristics were well balanced (mean age 59.1 years, 63% male, and follow‐up 1.50 years [162 970 patient‐years]). Compared to oGLD group, SGLT‐2i group had lower risk of cardiorenal disease, HF, CKD, stroke, and all‐cause mortality with HRs (95% confidence intervals) 0.55 (0.49‐0.61), 0.73 (0.61‐0.87), 0.45 (0.39‐0.52), 0.69 (0.59‐0.81), and 0.52 (0.46‐0.58), respectively, while no difference in MI. These were consistent in 1:1 propensity‐score matching analysis between SGLT‐2i and DPP‐4i users (n = 17 232 in each group). Conclusions In Japanese CVRD‐free T2D patients, SGLT‐2i initiation was associated with lower risk of cardiorenal diseases, stroke, and all‐cause mortality compared to oGLD, suggesting preventive effect of SGLT‐2i treatment in the early stage of T2D patients without CVRD manifestation.

With the widespread use of electronic medical records and administrative claims databases, analytic results from so‐called real‐world data have become increasingly important in healthcare decision‐making. Diabetes mellitus is a heterogeneous condition that involves a broad spectrum of patients. Real‐world database studies have been recognised as a powerful tool to understand the impact of current practices on clinical courses and outcomes, such as long‐term glucose control, development of microvascular or macro‐vascular diseases, and mortality. Diabetes is also a major global health issue and poses a significant social and economic burden worldwide. Therefore, it is critical to understand the epidemiology, clinical course, treatment reality, and long‐term outcomes of diabetes to determine realistic solutions to a variety of disease‐related issues that we are facing. In the present review, we summarise the healthcare system and large‐scale databases currently available in Japan, introduce the results from recent database studies involving Japanese patients with diabetes, and discuss future opportunities and challenges for the use of databases in the management of diabetes.