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
https://doi.org/10.14341/DM13029
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.
CONCLUSION: 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.
About the Authors
A. Kashiwagi
Omi Medical Center
Japan
Competing Interests:
Japan
Shiga
Competing Interests:
Получал финансирование в качестве консультанта группы Sunstar.
S. Shoji
Medical Affairs, Astellas Pharma Inc.
Japan
Competing Interests:
Japan
Tokyo
Competing Interests:
Сотрудник Astellas Pharma Inc., Tokyo, Japan
S. Onozawa
Advanced Informatics & Analytics, Astellas Pharma Inc.
Japan
Competing Interests:
Japan
Tokyo
Competing Interests:
Сотрудник Astellas Pharma Inc., Tokyo, Japan
Y. Kosakai
Medical Affairs, Astellas Pharma Inc.
Japan
Competing Interests:
Japan
Tokyo
Competing Interests:
Сотрудник Astellas Pharma Inc., Tokyo, Japan
M. Waratani
Advanced Informatics & Analytics, Astellas Pharma Inc.
Japan
Competing Interests:
Japan
Tokyo
Competing Interests:
Бывший сотрудник Astellas Pharma Inc. Сменила место работы после завершения исследования; в настоящее время работает директором по исследованиям экономики здравоохранения и результатов, медицинские вопросы, Alexion Pharma GK Alexion-AstraZeneca Rare Disease, AstraZeneca.
Yu. Ito
Medical Affairs, Astellas Pharma Inc.
Japan
Competing Interests:
Japan
Tokyo
Competing Interests:
Сотрудник Astellas Pharma Inc., Tokyo, Japan
References
1. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373: 2117-2128.
2. Fitchett D, Inzucchi SE, Cannon CP, et al. Empagliflozin reduced mortality and hospitalization for heart failure across the spectrum of cardiovascular risk in the EMPA-REG OUTCOME trial. Circulation 2019; 139: 1384—1395.
3. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377: 644-657.
4. Radholm K, Figtree G, Perkovic V, et al. Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS program. Circulation 2018; 138: 458-468.
5. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380: 347-357.
6. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380: 2295-2306.
7. Kosiborod M, Lam CSP, Kohsaka S, et al. Cardiovascular events associated with SGLT-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL 2 study. J Am Coll Cardiol 2018; 71: 2628-2639.
8. Cavender MA, Norhammar A, Birkeland KI, et al. SGLT-2 inhibitors and cardiovascular risk: an analysis of CVD-REAL. J Am Coll Cardiol 2018; 71: 2497-2506.
9. Kosiborod M, Cavender MA, Fu AZ, et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors). Circulation 2017; 136: 249-259.
10. Han SJ, Ha KH, Lee N, et al. Effectiveness and safety of sodium-glucose co-transporter-2 inhibitors compared with dipeptidyl peptidase-4 inhibitors in older adults with type 2 diabetes: a nationwide population-based study. Diabetes Obes Metab 2021; 23: 682-691.
11. Kohsaka S, Takeda M, Bodegard J, et al. Sodium-glucose cotransporter 2 inhibitors compared with other glucose¬lowering drugs in Japan: subanalyses of the CVD-REAL 2 Study. J Diabetes Investig 2021; 12: 67-73.
12. Birkeland KI, Bodegard J, Banerjee A, et al. Lower cardiorenal risk with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes without cardiovascular and renal diseases: a large multinational observational study. Diabetes Obes Metab 2021; 23: 75-85.
13. Komuro I, Kadowaki T, Bodegard J, et al. Lower heart failure and chronic kidney disease risks associated with sodium- glucose cotransporter-2 inhibitor use in Japanese type 2 diabetes patients without established cardiovascular and renal diseases. Diabetes Obes Metab 2021; 23(Suppl 2): 19-27.
14. Araki E, Tanaka A, Inagaki N, et al. Diagnosis, prevention, and treatment of cardiovascular diseases in people with type 2 diabetes and prediabetes - a consensus statement jointly from the Japanese Circulation Society and the Japan Diabetes Society. Circ J 2020; 85: 82-125.
15. Araki E, Goto A, Kondo T, et al. Japanese clinical practice guideline for Diabetes 2019. Diabetol Int 2020; 11: 165-223.
16. Nishimura R, Kato H, Kisanuki K, et al. Treatment patterns, persistence and adherence rates in patients with type 2 diabetes mellitus in Japan: a claims-based cohort study. BMJ Open 2019; 9: e025806.
17. Tanaka S, Seto K, Kawakami K. Pharmacoepidemiology in Japan: medical databases and research achievements. J Pharm Health Care Sci 2015; 1:16.
18. Poole RM, Dungo RT. Ipragliflozin: first global approval. Drugs 2014; 74: 611-617.
19. Suzuki K, Hasegawa K, Watanabe M. Efficacy and patient satisfaction of dipeptidyl peptidase-4 inhibitor after switching from once-daily DPP-4 inhibitor to once-weekly regimen. J Clin Med Res 2018; 10: 641-647.
20. Chang HY, Weiner JP, Richards TM, et al. Validating the adapted Diabetes Complications Severity Index in claims data. Am J Manag Care 2012; 18: 721-726.
21. Kashiwagi A, Araki S, Maegawa H. Sodium-glucose cotransporter 2 inhibitors represent a paradigm shift in the prevention of heart failure in type 2 diabetes patients. J Diabetes Investig 2021; 12: 6-20.
22. Oka S, Kai T, Hoshino K, et al. Effects of empagliflozin in different phases of diabetes mellitus-related cardiomyopathy: a prospective observational study. BMC Cardiovasc Disord 2021; 21: 217.
23. Kohsaka S, Lam CSP, Kim DJ, et al. Risk of cardiovascular events and death associated with initiation of SGLT2 inhibitors compared with DPP-4 inhibitors: an analysis from the CVD-REAL 2 multinational cohort study. Lancet Diabetes Endocrinol 2020; 8: 606-615.
24. Ito Y, Van Schyndle J, Nishimura T, et al. Characteristics of patients with diabetes initiating sodium glucose co¬transporter-2 inhibitors (SGLT2i): real-world results from three administrative databases in Japan. Diabetes Ther 2019; 10: 549-562.
25. Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020; 41: 255-323.
26. Suissa S. Reduced mortality with sodium-glucose cotransporter-2 inhibitors in observational studies: avoiding immortal time bias. Circulation 2018; 137: 1432¬1434.
27. Japanese Ministry of Health, Labour and Welfare. Vital Statistics of Japan 2019: Table 1-25 Number of deaths and percentage distribution by place of occurrence, by year [Internet]. 2019 [cited March 9, 2021]. Available from: https://www.mhlw.go.jp/english/database/db-hh/xlsx/1-25.xlsx.
Supplementary files
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1. Figure 1. Patient disposition. | |
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2. Figure 2. Forest plot of the risk of hospitalization for heart failure (hHF), all‐cause death (ACD), a composite of hHF or ACD, hospitalization for myocardial infarction (MI) and hospitalization for stroke, in the full cohort and in patients with and without a cardiovascular disease (CVD) history. | |
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3. Figure 3. Kaplan–Meier curve of cumulative rate of hospitalization for heart failure (hHF) in (a) the full cohort, (b) patients with a cardiovascular disease (CVD) history and (c) patients without a CVD history. The weighted cumulative hHF rate in sodium–glucose cotransporter 2 inhibitor (SGLT2i)‐treated patients was higher than that in dipeptidyl peptidase‐4 inhibitor (DPP4i)‐treated patients 30–60 days after the index date, in the full cohort and in patients with a CVD history; the cumulative hHF rate tended to be lower in SGLT2i‐treated patients than in DPP4i‐treated patients after 1 year from the index date. In contrast, among patients without a CVD history, the cumulative hHF rate in SGLT2i‐treated patients was lower at almost all time points from 90 days after the index date than in DPP4i‐treated patients. | |
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4. Figure 4 Kaplan–Meier curve of cumulative rate of all‐cause death (ACD) in (a) the full cohort, (b) patients with a cardiovascular disease (CVD) history, and (c) patients without a CVD history. The weighted cumulative rate of ACD was lower in sodium–glucose cotransporter 2 (SGLT2i)‐treated patients compared with dipeptidyl peptidase‐4 inhibitor (DPP4i)‐treated patients at all time points after initiation of the respective drugs in the full cohort and both CVD subcohorts. | |
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5. Figure 5 Kaplan–Meier curve of cumulative rate of the composite of hospitalization for heart failure (hHF) or all‐cause death (ACD) in (a) the full cohort, (b) patients with a cardiovascular disease (CVD) history and (c) patients without a CVD history. The weighted cumulative rate of the composite of hHF or ACD was lower in sodium–glucose cotransporter 2 inhibitor (SGLT2i)‐treated patients compared with dipeptidyl peptidase‐4 inhibitor (DPP4i)‐treated patients at almost all time points after initiation of the respective drugs in the full cohort and both CVD subcohorts. | |
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6. Figure 6 Subgroup analysis (<75 years; ≥75 years). Forest plot of the risk of hospitalization for heart failure (hHF), all‐cause death (ACD), hHF or ACD, hospitalization for myocardial infarction (MI), and hospitalization for stroke in (a) the full cohort, (b) patients with a cardiovascular disease (CVD) history and (c) patients without a CVD history. CI, confidence interval; DPP4i, dipeptidyl peptidase‐4 inhibitor; HR, hazard ratio; SGLT2i, sodium–glucose cotransporter 2 inhibitor. | |
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7. Figure S1. Study design. Note: The pre-index period, defined as the period between 1 year and 1 day before the index date, and the index date were used to confirm that an SGLT2i or a DPP4i was not previously prescribed and to establish patients’ baseline characteristics. | |
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For citations:
Kashiwagi A., Shoji S., Onozawa S., Kosakai Y., Waratani M., Ito Yu. 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. Diabetes mellitus. 2023;26(2):157-171. (In Russ.) https://doi.org/10.14341/DM13029
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