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Open Access 30-09-2024 | Diabetic Retinopathy | Original Research

Comparison of the Risk of Diabetic Retinopathy Between Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus in Japan: A Retrospective Analysis of Real-World Data

Authors: Masaya Koshizaka, Tomoaki Tatsumi, Fumiko Kiyonaga, Yoshinori Kosakai, Yoko Yoshinaga, Mami Shintani-Tachi

Published in: Diabetes Therapy

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Abstract

Introduction

Diabetic retinopathy (DR), a microvascular complication of type 2 diabetes mellitus (T2DM), is a leading cause of blindness and has detrimental effects on patients’ quality of life. We compared the risk of DR diagnosis with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with T2DM in Japan.

Methods

This Japanese retrospective cohort study used the JMDC Claims Database (data collected from January 2015 to September 2022). Patients with T2DM and no record of microvascular or macrovascular diseases who were newly treated with an SGLT2i (23,061 patients) or a DPP-4i (53,986 patients) were matched 1:1 using propensity score (10,166 per matched group). Incidence rates (IRs) and cumulative IRs of DR diagnosis were calculated for each treatment group; hazard ratio (HR) and its 95% confidence interval (CI) were calculated using Cox proportional hazard models to compare the risk between the groups.

Results

The IR of DR diagnosis was 46.23 and 57.12 per 1000 person-years in the SGLT2i and DPP-4i groups, respectively, with a significantly lower risk in the SGLT2i group than in the DPP-4i group (HR 0.83, 95% CI 0.75–0.92, P = 0.0003).

Conclusions

In this study, the risk of DR diagnosis was lower with SGLT2i compared with DPP-4i in patients with T2DM without microvascular and macrovascular diseases in Japan. Findings suggest that early SGLT2i treatment may be beneficial in preventing DR development in early-stage T2DM.
Graphical abstract available for this article.

Graphical Abstract

Appendix
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Literature
1.
go back to reference Yang Z, Tan TE, Shao Y, Wong TY, Li X. Classification of diabetic retinopathy: past, present and future. Front Endocrinol (Lausanne). 2022;13:1079217.CrossRefPubMed Yang Z, Tan TE, Shao Y, Wong TY, Li X. Classification of diabetic retinopathy: past, present and future. Front Endocrinol (Lausanne). 2022;13:1079217.CrossRefPubMed
2.
go back to reference Tan TE, Wong TY. Diabetic retinopathy: looking forward to 2030. Front Endocrinol (Lausanne). 2023;13:1077669.CrossRefPubMed Tan TE, Wong TY. Diabetic retinopathy: looking forward to 2030. Front Endocrinol (Lausanne). 2023;13:1077669.CrossRefPubMed
3.
go back to reference Kawasaki R, Tanaka S, Tanaka S, Yamamoto T, Sone H, Ohashi Y, et al. Incidence and progression of diabetic retinopathy in Japanese adults with type 2 diabetes: 8 year follow-up study of the Japan diabetes complications study (JDCS). Diabetologia. 2011;54(9):2288–94.CrossRefPubMed Kawasaki R, Tanaka S, Tanaka S, Yamamoto T, Sone H, Ohashi Y, et al. Incidence and progression of diabetic retinopathy in Japanese adults with type 2 diabetes: 8 year follow-up study of the Japan diabetes complications study (JDCS). Diabetologia. 2011;54(9):2288–94.CrossRefPubMed
4.
go back to reference Teo ZL, Tham YC, Yu M, Chee ML, Rim TH, Cheung N, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology. 2021;128(11):1580–91.CrossRefPubMed Teo ZL, Tham YC, Yu M, Chee ML, Rim TH, Cheung N, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology. 2021;128(11):1580–91.CrossRefPubMed
5.
go back to reference Singh RP, Elman MJ, Singh SK, Fung AE, Stoilov I. Advances in the treatment of diabetic retinopathy. J Diabetes Complicat. 2019;33(12): 107417.CrossRef Singh RP, Elman MJ, Singh SK, Fung AE, Stoilov I. Advances in the treatment of diabetic retinopathy. J Diabetes Complicat. 2019;33(12): 107417.CrossRef
6.
go back to reference Mahobia A, Sahoo SR, Maiti N, Sathyanarayanan R, Aravinth R, Pandraveti RR, et al. Diabetic retinopathy and its effect on quality of life: an original research. J Pharm Bioallied Sci. 2021;13(Suppl 2):S1365–8.CrossRefPubMed Mahobia A, Sahoo SR, Maiti N, Sathyanarayanan R, Aravinth R, Pandraveti RR, et al. Diabetic retinopathy and its effect on quality of life: an original research. J Pharm Bioallied Sci. 2021;13(Suppl 2):S1365–8.CrossRefPubMed
7.
go back to reference Pereira DM, Shah A, D’Souza M, Simon P, George T, D’Souza N, et al. Quality of life in people with diabetic retinopathy: Indian study. J Clin Diagn Res. 2017;11(4):NC01-NC6.PubMed Pereira DM, Shah A, D’Souza M, Simon P, George T, D’Souza N, et al. Quality of life in people with diabetic retinopathy: Indian study. J Clin Diagn Res. 2017;11(4):NC01-NC6.PubMed
8.
go back to reference Fenwick E, Rees G, Pesudovs K, Dirani M, Kawasaki R, Wong TY, et al. Social and emotional impact of diabetic retinopathy: a review. Clin Exp Ophthalmol. 2012;40(1):27–38.CrossRefPubMed Fenwick E, Rees G, Pesudovs K, Dirani M, Kawasaki R, Wong TY, et al. Social and emotional impact of diabetic retinopathy: a review. Clin Exp Ophthalmol. 2012;40(1):27–38.CrossRefPubMed
9.
go back to reference Kashiwagi A, Shoji S, Kosakai Y, Koga T, Asakawa K, Rokuda M. 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. J Diabetes Investig. 2023;14(3):404–16.CrossRefPubMed Kashiwagi A, Shoji S, Kosakai Y, Koga T, Asakawa K, Rokuda M. 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. J Diabetes Investig. 2023;14(3):404–16.CrossRefPubMed
10.
go back to reference Ott C, Jumar A, Striepe K, Friedrich S, Karg MV, Bramlage P, et al. A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation. Cardiovasc Diabetol. 2017;16(1):26.CrossRefPubMed Ott C, Jumar A, Striepe K, Friedrich S, Karg MV, Bramlage P, et al. A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation. Cardiovasc Diabetol. 2017;16(1):26.CrossRefPubMed
11.
go back to reference Lin TY, Kang EY, Shao SC, Lai EC, Garg SJ, Chen KJ, et al. Risk of diabetic retinopathy between sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Diabetes Metab J. 2023;47(3):394–404.CrossRefPubMed Lin TY, Kang EY, Shao SC, Lai EC, Garg SJ, Chen KJ, et al. Risk of diabetic retinopathy between sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Diabetes Metab J. 2023;47(3):394–404.CrossRefPubMed
12.
go back to reference Chung YR, Ha KH, Lee K, Kim DJ. Effects of sodium-glucose cotransporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors on diabetic retinopathy and its progression: a real-world Korean study. PLoS ONE. 2019;14(10): e0224549.CrossRefPubMed Chung YR, Ha KH, Lee K, Kim DJ. Effects of sodium-glucose cotransporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors on diabetic retinopathy and its progression: a real-world Korean study. PLoS ONE. 2019;14(10): e0224549.CrossRefPubMed
13.
go back to reference Huang ST, Bair PJ, Chang SS, Kao YN, Chen SN, Wang IK, et al. Risk of diabetic retinopathy in patients with type 2 diabetes after SGLT-2 inhibitors: a nationwide population cohort study. Clin Pharmacol Ther. 2024;115(1):95–103.CrossRefPubMed Huang ST, Bair PJ, Chang SS, Kao YN, Chen SN, Wang IK, et al. Risk of diabetic retinopathy in patients with type 2 diabetes after SGLT-2 inhibitors: a nationwide population cohort study. Clin Pharmacol Ther. 2024;115(1):95–103.CrossRefPubMed
14.
go back to reference Komuro I, Kadowaki T, Bodegård J, Thuresson M, Okami S, Yajima T. 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.CrossRefPubMed Komuro I, Kadowaki T, Bodegård J, Thuresson M, Okami S, Yajima T. 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.CrossRefPubMed
15.
go back to reference Herat LY, Matthews VB, Rakoczy PE, Carnagarin R, Schlaich M. Focusing on sodium glucose cotransporter-2 and the sympathetic nervous system: potential impact in diabetic retinopathy. Int J Endocrinol. 2018;2018:9254126.CrossRefPubMed Herat LY, Matthews VB, Rakoczy PE, Carnagarin R, Schlaich M. Focusing on sodium glucose cotransporter-2 and the sympathetic nervous system: potential impact in diabetic retinopathy. Int J Endocrinol. 2018;2018:9254126.CrossRefPubMed
16.
go back to reference Sha W, Wen S, Chen L, Xu B, Lei T, Zhou L. The role of SGLT2 inhibitor on the treatment of diabetic retinopathy. J Diabetes Res. 2020;2020:8867875.CrossRefPubMed Sha W, Wen S, Chen L, Xu B, Lei T, Zhou L. The role of SGLT2 inhibitor on the treatment of diabetic retinopathy. J Diabetes Res. 2020;2020:8867875.CrossRefPubMed
17.
go back to reference Wakisaka M, Nagao T. Sodium glucose cotransporter 2 in mesangial cells and retinal pericytes and its implications for diabetic nephropathy and retinopathy. Glycobiology. 2017;27(8):691–5.CrossRefPubMed Wakisaka M, Nagao T. Sodium glucose cotransporter 2 in mesangial cells and retinal pericytes and its implications for diabetic nephropathy and retinopathy. Glycobiology. 2017;27(8):691–5.CrossRefPubMed
18.
go back to reference Yamato M, Kato N, Yamada K-I, Inoguchi T. The early pathogenesis of diabetic retinopathy and its attenuation by sodium–glucose transporter 2 inhibitors. Diabetes. 2024;73(7):1153–66.CrossRefPubMed Yamato M, Kato N, Yamada K-I, Inoguchi T. The early pathogenesis of diabetic retinopathy and its attenuation by sodium–glucose transporter 2 inhibitors. Diabetes. 2024;73(7):1153–66.CrossRefPubMed
19.
go back to reference Wołos-Kłosowicz K, Matuszewski W, Rutkowska J, Krankowska K, Bandurska-Stankiewicz E. Will GLP-1 analogues and SGLT-2 inhibitors become new game changers for diabetic retinopathy? J Clin Med. 2022;11(20):6183.CrossRefPubMed Wołos-Kłosowicz K, Matuszewski W, Rutkowska J, Krankowska K, Bandurska-Stankiewicz E. Will GLP-1 analogues and SGLT-2 inhibitors become new game changers for diabetic retinopathy? J Clin Med. 2022;11(20):6183.CrossRefPubMed
20.
go back to reference May M, Framke T, Junker B, Framme C, Pielen A, Schindler C. How and why SGLT2 inhibitors should be explored as potential treatment option in diabetic retinopathy: clinical concept and methodology. Ther Adv Endocrinol Metab. 2019;10:2042018819891886.CrossRefPubMed May M, Framke T, Junker B, Framme C, Pielen A, Schindler C. How and why SGLT2 inhibitors should be explored as potential treatment option in diabetic retinopathy: clinical concept and methodology. Ther Adv Endocrinol Metab. 2019;10:2042018819891886.CrossRefPubMed
21.
go back to reference Takakura S, Toyoshi T, Hayashizaki Y, Takasu T. Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats. Life Sci. 2016;147:125–31.CrossRefPubMed Takakura S, Toyoshi T, Hayashizaki Y, Takasu T. Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats. Life Sci. 2016;147:125–31.CrossRefPubMed
22.
go back to reference Mudaliar S, Hupfeld C, Chao DL. SGLT2 inhibitor-induced low-grade ketonemia ameliorates retinal hypoxia in diabetic retinopathy-a novel hypothesis. J Clin Endocrinol Metab. 2021;106(5):1235–44.CrossRefPubMed Mudaliar S, Hupfeld C, Chao DL. SGLT2 inhibitor-induced low-grade ketonemia ameliorates retinal hypoxia in diabetic retinopathy-a novel hypothesis. J Clin Endocrinol Metab. 2021;106(5):1235–44.CrossRefPubMed
23.
go back to reference Ting DSW, Cheung GCM, Wong TY. Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. Clin Exp Ophthalmol. 2016;44(4):260–77.CrossRefPubMed Ting DSW, Cheung GCM, Wong TY. Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. Clin Exp Ophthalmol. 2016;44(4):260–77.CrossRefPubMed
24.
go back to reference Ciulla TA, Amador AG, Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care. 2003;26(9):2653–64.CrossRefPubMed Ciulla TA, Amador AG, Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care. 2003;26(9):2653–64.CrossRefPubMed
25.
go back to reference Murugesan N, Üstunkaya T, Feener EP. Thrombosis and hemorrhage in diabetic retinopathy: a perspective from an inflammatory standpoint. Semin Thromb Hemost. 2015;41(6):659–64.CrossRefPubMed Murugesan N, Üstunkaya T, Feener EP. Thrombosis and hemorrhage in diabetic retinopathy: a perspective from an inflammatory standpoint. Semin Thromb Hemost. 2015;41(6):659–64.CrossRefPubMed
26.
go back to reference Kollias AN, Ulbig MW. Diabetic retinopathy: early diagnosis and effective treatment. Dtsch Arztebl Int. 2010;107(5):75–83.PubMed Kollias AN, Ulbig MW. Diabetic retinopathy: early diagnosis and effective treatment. Dtsch Arztebl Int. 2010;107(5):75–83.PubMed
27.
go back to reference Newman DK. Surgical management of the late complications of proliferative diabetic retinopathy. Eye (Lond). 2010;24(3):441–9.CrossRefPubMed Newman DK. Surgical management of the late complications of proliferative diabetic retinopathy. Eye (Lond). 2010;24(3):441–9.CrossRefPubMed
28.
go back to reference Tang Y, Shi Y, Fan Z. The mechanism and therapeutic strategies for neovascular glaucoma secondary to diabetic retinopathy. Front Endocrinol (Lausanne). 2023;14:1102361.CrossRefPubMed Tang Y, Shi Y, Fan Z. The mechanism and therapeutic strategies for neovascular glaucoma secondary to diabetic retinopathy. Front Endocrinol (Lausanne). 2023;14:1102361.CrossRefPubMed
29.
go back to reference Ohsugi M, Eiki J-I, Iglay K, Tetsuka J, Tokita S, Ueki K. Comorbidities and complications in Japanese patients with type 2 diabetes mellitus: retrospective analyses of J-DREAMS, an advanced electronic medical records database. Diabetes Res Clin Pract. 2021;178: 108845.CrossRefPubMed Ohsugi M, Eiki J-I, Iglay K, Tetsuka J, Tokita S, Ueki K. Comorbidities and complications in Japanese patients with type 2 diabetes mellitus: retrospective analyses of J-DREAMS, an advanced electronic medical records database. Diabetes Res Clin Pract. 2021;178: 108845.CrossRefPubMed
30.
go back to reference Katakami N, Mita T, Takahara M, Yajima T, Wada F, Kawashima M, et al. Baseline characteristics of patients with type 2 diabetes initiating second-line treatment in Japan: findings from the J-DISCOVER study. Diabetes Ther. 2020;11(7):1563–78.CrossRefPubMed Katakami N, Mita T, Takahara M, Yajima T, Wada F, Kawashima M, et al. Baseline characteristics of patients with type 2 diabetes initiating second-line treatment in Japan: findings from the J-DISCOVER study. Diabetes Ther. 2020;11(7):1563–78.CrossRefPubMed
Metadata
Title
Comparison of the Risk of Diabetic Retinopathy Between Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus in Japan: A Retrospective Analysis of Real-World Data
Authors
Masaya Koshizaka
Tomoaki Tatsumi
Fumiko Kiyonaga
Yoshinori Kosakai
Yoko Yoshinaga
Mami Shintani-Tachi
Publication date
30-09-2024
Publisher
Springer Healthcare
Published in
Diabetes Therapy
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI
https://doi.org/10.1007/s13300-024-01649-9

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