Reduction in cardiovascular disease events in patients with type 2 diabetes mellitus treated with a sodium–glucose cotransporter 2 inhibitor versus a dipeptidyl peptidase‐4 inhibitor: A real‐world retrospective administrative database analysis in Japan

Abstract

Aims/Introduction To evaluate the benefit of sodium–glucose cotransporter 2 inhibitors (SGLT2i) versus dipeptidyl peptidase‐4 inhibitors (DPP4i) in reducing cardiovascular disease (CVD) events in patients with type 2 diabetes mellitus with and without a CVD history. Materials and Methods This retrospective cohort study used Japanese hospital administrative data from the Medical Data Vision database (January 2015 to April 2020). Patients with type 2 diabetes mellitus ( n = 625,739) who were new users of an SGLT2i ( n = 57,070; 9.1%) or DPP4i ( n = 568,669; 90.9%) were included. Outcomes included hospitalization for heart failure (hHF), all‐cause death (ACD) and the composite of hHF or ACD. Hazard ratios (HR) were calculated using the inverse probability weighting Cox proportional hazards model to compare CVD event risks between treatment groups. Results Compared with DPP4i, SGLT2i was associated with a significant reduction in hHF risk among patients without a CVD history (HR 0.507, 95% confidence interval 0.283–0.907), but not in the full cohort or those with a CVD history. SGLT2i was associated with a significant risk reduction of ACD (HR 0.592, 95% confidence interval 0.481–0.729) and the composite of hHF or ACD (HR 0.712, 95% confidence interval 0.613–0.826), compared with DPP4i in the full cohort; similar results were observed among patients with and without a CVD history. Conclusions In this real‐world study, SGLT2i versus DPP4i was associated with a significant reduction in hHF, ACD and hHF or ACD events in patients with type 2 diabetes mellitus without a CVD history.

Healthcare resource utilization and healthcare costs in patients with type 2 diabetes mellitus initiating sodium‐glucose cotransporter 2 inhibitors vs dipeptidyl peptidase‐4 inhibitors in Japan: A real‐world administrative database analysis

“…In this study, mean all-cause overall healthcare costs were also significantly lower in patients treated with an SGLT2i ($364.2 PPPM or $4,370.8 per person per year) vs a DPP4i ($420.3 PPPM or $5,044.1 per person per year). This is mainly attributed to the difference in the overall hospitalization costs between SGLT2i and DPP4i, consistent with the results of previous studies [9][10][11][12] . Together, the results indicate that SGLT2i are associated with reduced HCRU and healthcare costs, particularly in relation to hospitalization, compared with DPP4i in patients with type 2 diabetes mellitus in Japan; hospitalization greatly impacts HCRU and healthcare costs in patients with type 2 diabetes mellitus, and the economic benefits of SGLT2i are dependent on its effects of reducing hospitalization.…”

“…SGLT2i is associated with an increased risk of diabetic ketoacidosis 23,24 and genitourinary infections [25][26][27] ; as such, the higher outpatient visit costs may be due to the costs of blood and urine testing to monitor potential SGLT2i-related adverse events. Conversely, given that SGLT2i have cardiorenal and hepatoprotective effects [9][10][11][12]28,29 , they may have been prescribed to patients with more severe comorbidities and complications, although information on severity is unknown. To monitor comorbidities and complications, patients may have had more medical examinations at each outpatient visit, and the costs of such examinations may have also contributed to the higher outpatient visit costs with SGLT2i.…”

Cardiometabolic risk reductions in patients with type 2 diabetes mellitus newly treated with a sodium–glucose cotransporter 2 inhibitor versus a dipeptidyl peptidase‐4 inhibitor: A real‐world administrative database study in Japan

“…Given that the current type 2 diabetes mellitus treatment guideline recommends to also focus on managing CVD risk factors, these results support the clinical significance of using SGLT2i. In fact, in a previous study 17 , SGLT2i were associated with a significant reduction in CVD events in Japanese patients with type 2 diabetes mellitus, including those without a CVD history. Therefore, SGLT2i might show cardioprotective effects in patients without CVD when initiated early and should not be excluded as a first-line treatment option for type 2 diabetes mellitus.…”

“…Eligible patients were aged ≥18 years, had one or more prescription record for an SGLT2i or a DPP4i in the enrollment period (1 January 2015–31 March 2020; Figure S1; index treatment codes were reported previously 17 ) and had a diagnosis of type 2 diabetes mellitus (International Classification of Diseases, 10th Revision [ICD‐10]: E11.x) or unspecified diabetes mellitus (ICD‐10: E14x). Patients excluded had type 1 diabetes mellitus (ICD‐10: E10.x) diagnosis on or before the index date (date of first recorded receipt of an SGLT2i or a DPP4i on or after January 1, 2015); gestational diabetes (ICD‐10: O24.x) diagnosis in the pre‐index period (time between 1 year and 1 day before the index date) or on the index date; prescription records for an SGLT2i and/or a DPP4i, including those in a fixed‐dose combination of SGLT2i and DPP4i, during the pre‐index period or on the index date; or <1 year of record in the database on or before the index date.…”

“…Baseline characteristics, including age, comorbidities, Charlson Comorbidity Index (CCI) 23 and adapted Diabetes Complication Severity Index (aDCSI) scores 24 , and concomitant medications, collected during the pre‐index period and on the index date, were summarized using descriptive statistics. Codes for CCI have been previously reported 17 , and codes for aDCSI and other relevant codes are shown in Tables S1–S4. Covariates in the logistic regression model were demographics (sex, age), smoking history, metabolic measurements (HbA1c, BMI, SBP) in the baseline period, CCI, aDCSI, coronary revascularization and relevant medication use in the baseline period.…”