Association of long-term use of dipeptidyl peptidase-4 inhibitors with the risk of diabetic retinopathy in patients with diabetes mellitus: a real-world evidence study
BackgroundIn this study, we investigated the association of long-term use of a dipeptidyl peptidase-4 inhibitor (DPP-4i) with the risk of diabetic retinopathy (DR) in patients with diabetes mellitus (DM).MethodsThis study was a secondary analysis based on the nationwide database from 2008 to 2022 in...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-04-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1518545/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849725892292509696 |
|---|---|
| author | Yu-Ching Li Yu-Ching Li Yu-Hsiang Kuan Yu-Hsiang Kuan Yih Yang Shuo-Yan Gau Kun-Yu Su Tung-Han Tsai Kuang-Hua Huang Chien-Ying Lee Chien-Ying Lee |
| author_facet | Yu-Ching Li Yu-Ching Li Yu-Hsiang Kuan Yu-Hsiang Kuan Yih Yang Shuo-Yan Gau Kun-Yu Su Tung-Han Tsai Kuang-Hua Huang Chien-Ying Lee Chien-Ying Lee |
| author_sort | Yu-Ching Li |
| collection | DOAJ |
| description | BackgroundIn this study, we investigated the association of long-term use of a dipeptidyl peptidase-4 inhibitor (DPP-4i) with the risk of diabetic retinopathy (DR) in patients with diabetes mellitus (DM).MethodsThis study was a secondary analysis based on the nationwide database from 2008 to 2022 in Taiwan. Patients with new-onset DM who were treated with either a DPP-4i or sulfonylurea from 2009 to 2017 were included in this study. Patients who received a DPP-4i were included in the case group and further divided on the basis of the cumulative defined daily dose (cDDD) as follows: ≤90, 91–180, 181–300, and >300 cDDD. Propensity score matching was performed to select patients who used a sulfonylurea, and these patients were assigned to the control group. With adjustment for sex, age, income, urbanization level, comorbidities, and other anti-diabetic agents, the Cox proportional hazard model was used to estimate the risk of DR associated with DPP-4i use over the 5-year follow-up.ResultsThere were 83,503 patients with DPP-4i use and 167,006 patients with sulfonylurea use after matching. Compared with patients with sulfonylurea use, patients with DPP-4i use at ≤90 cDDD had a hazard ratio (HR) of 1.43 (95% confidence interval [CI] = 1.38–1.49) for DR development, whereas those with DPP-4i use at 91–180, 181–300 or >300 cDDD had HRs of 1.66 (95% CI: 1.59–1.74), 1.82 (95% CI: 1.74–1.90), and 2.32 (95% CI: 1.91–2.82) for DR development, respectively. Of the different DPP-4is, linagliptin at ≤90 or 181–300 was associated with the highest risk of DR. Significant differences were discovered at ≤90, 91–181, and 181–300 cDDD in the risk of DR between patients using Saxagliptin versus sitagliptin. Vildagliptin at ≤90 or 91–180 cDDD was associated with an increased risk of DR, but not at 181–300 cDDD.ConclusionIn patients with DM, DPP-4i at ≤90, 91–180, 181–300 and >300 cDDD was linked to an increased risk of DR over the 5-year follow-up. Sitagliptin at cDDD 181–300 was associated with the greatest DR risk. The potential for DPP-4i to accelerate DR progression should be considered. |
| format | Article |
| id | doaj-art-324ee3a5f23146e2a537aa49ee40e9c6 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-324ee3a5f23146e2a537aa49ee40e9c62025-08-20T03:10:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15185451518545Association of long-term use of dipeptidyl peptidase-4 inhibitors with the risk of diabetic retinopathy in patients with diabetes mellitus: a real-world evidence studyYu-Ching Li0Yu-Ching Li1Yu-Hsiang Kuan2Yu-Hsiang Kuan3Yih Yang4Shuo-Yan Gau5Kun-Yu Su6Tung-Han Tsai7Kuang-Hua Huang8Chien-Ying Lee9Chien-Ying Lee10Department of Public Health, China Medical University, Taichung, TaiwanDivision of Family Medicine, Yuan Rung Hospital, Changhua, TaiwanDepartment of Pharmacology, Chung Shan Medical University, Taichung, TaiwanDepartment of Pharmacy, Chung Shan Medical University Hospital, Taichung, TaiwanDepartment of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, TaiwanDepartment of Business Administration, National Taiwan University, Taipei, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung, TaiwanDepartment of Health Services Administration, China Medical University, Taichung, TaiwanDepartment of Health Services Administration, China Medical University, Taichung, TaiwanDepartment of Pharmacology, Chung Shan Medical University, Taichung, TaiwanDepartment of Pharmacy, Chung Shan Medical University Hospital, Taichung, TaiwanBackgroundIn this study, we investigated the association of long-term use of a dipeptidyl peptidase-4 inhibitor (DPP-4i) with the risk of diabetic retinopathy (DR) in patients with diabetes mellitus (DM).MethodsThis study was a secondary analysis based on the nationwide database from 2008 to 2022 in Taiwan. Patients with new-onset DM who were treated with either a DPP-4i or sulfonylurea from 2009 to 2017 were included in this study. Patients who received a DPP-4i were included in the case group and further divided on the basis of the cumulative defined daily dose (cDDD) as follows: ≤90, 91–180, 181–300, and >300 cDDD. Propensity score matching was performed to select patients who used a sulfonylurea, and these patients were assigned to the control group. With adjustment for sex, age, income, urbanization level, comorbidities, and other anti-diabetic agents, the Cox proportional hazard model was used to estimate the risk of DR associated with DPP-4i use over the 5-year follow-up.ResultsThere were 83,503 patients with DPP-4i use and 167,006 patients with sulfonylurea use after matching. Compared with patients with sulfonylurea use, patients with DPP-4i use at ≤90 cDDD had a hazard ratio (HR) of 1.43 (95% confidence interval [CI] = 1.38–1.49) for DR development, whereas those with DPP-4i use at 91–180, 181–300 or >300 cDDD had HRs of 1.66 (95% CI: 1.59–1.74), 1.82 (95% CI: 1.74–1.90), and 2.32 (95% CI: 1.91–2.82) for DR development, respectively. Of the different DPP-4is, linagliptin at ≤90 or 181–300 was associated with the highest risk of DR. Significant differences were discovered at ≤90, 91–181, and 181–300 cDDD in the risk of DR between patients using Saxagliptin versus sitagliptin. Vildagliptin at ≤90 or 91–180 cDDD was associated with an increased risk of DR, but not at 181–300 cDDD.ConclusionIn patients with DM, DPP-4i at ≤90, 91–180, 181–300 and >300 cDDD was linked to an increased risk of DR over the 5-year follow-up. Sitagliptin at cDDD 181–300 was associated with the greatest DR risk. The potential for DPP-4i to accelerate DR progression should be considered.https://www.frontiersin.org/articles/10.3389/fphar.2025.1518545/fulldiabetic retinopathydipeptidyl peptidase-4 inhibitorsdiabetes mellituscumulative defined daily dosereal-world evidence |
| spellingShingle | Yu-Ching Li Yu-Ching Li Yu-Hsiang Kuan Yu-Hsiang Kuan Yih Yang Shuo-Yan Gau Kun-Yu Su Tung-Han Tsai Kuang-Hua Huang Chien-Ying Lee Chien-Ying Lee Association of long-term use of dipeptidyl peptidase-4 inhibitors with the risk of diabetic retinopathy in patients with diabetes mellitus: a real-world evidence study Frontiers in Pharmacology diabetic retinopathy dipeptidyl peptidase-4 inhibitors diabetes mellitus cumulative defined daily dose real-world evidence |
| title | Association of long-term use of dipeptidyl peptidase-4 inhibitors with the risk of diabetic retinopathy in patients with diabetes mellitus: a real-world evidence study |
| title_full | Association of long-term use of dipeptidyl peptidase-4 inhibitors with the risk of diabetic retinopathy in patients with diabetes mellitus: a real-world evidence study |
| title_fullStr | Association of long-term use of dipeptidyl peptidase-4 inhibitors with the risk of diabetic retinopathy in patients with diabetes mellitus: a real-world evidence study |
| title_full_unstemmed | Association of long-term use of dipeptidyl peptidase-4 inhibitors with the risk of diabetic retinopathy in patients with diabetes mellitus: a real-world evidence study |
| title_short | Association of long-term use of dipeptidyl peptidase-4 inhibitors with the risk of diabetic retinopathy in patients with diabetes mellitus: a real-world evidence study |
| title_sort | association of long term use of dipeptidyl peptidase 4 inhibitors with the risk of diabetic retinopathy in patients with diabetes mellitus a real world evidence study |
| topic | diabetic retinopathy dipeptidyl peptidase-4 inhibitors diabetes mellitus cumulative defined daily dose real-world evidence |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1518545/full |
| work_keys_str_mv | AT yuchingli associationoflongtermuseofdipeptidylpeptidase4inhibitorswiththeriskofdiabeticretinopathyinpatientswithdiabetesmellitusarealworldevidencestudy AT yuchingli associationoflongtermuseofdipeptidylpeptidase4inhibitorswiththeriskofdiabeticretinopathyinpatientswithdiabetesmellitusarealworldevidencestudy AT yuhsiangkuan associationoflongtermuseofdipeptidylpeptidase4inhibitorswiththeriskofdiabeticretinopathyinpatientswithdiabetesmellitusarealworldevidencestudy AT yuhsiangkuan associationoflongtermuseofdipeptidylpeptidase4inhibitorswiththeriskofdiabeticretinopathyinpatientswithdiabetesmellitusarealworldevidencestudy AT yihyang associationoflongtermuseofdipeptidylpeptidase4inhibitorswiththeriskofdiabeticretinopathyinpatientswithdiabetesmellitusarealworldevidencestudy AT shuoyangau associationoflongtermuseofdipeptidylpeptidase4inhibitorswiththeriskofdiabeticretinopathyinpatientswithdiabetesmellitusarealworldevidencestudy AT kunyusu associationoflongtermuseofdipeptidylpeptidase4inhibitorswiththeriskofdiabeticretinopathyinpatientswithdiabetesmellitusarealworldevidencestudy AT tunghantsai associationoflongtermuseofdipeptidylpeptidase4inhibitorswiththeriskofdiabeticretinopathyinpatientswithdiabetesmellitusarealworldevidencestudy AT kuanghuahuang associationoflongtermuseofdipeptidylpeptidase4inhibitorswiththeriskofdiabeticretinopathyinpatientswithdiabetesmellitusarealworldevidencestudy AT chienyinglee associationoflongtermuseofdipeptidylpeptidase4inhibitorswiththeriskofdiabeticretinopathyinpatientswithdiabetesmellitusarealworldevidencestudy AT chienyinglee associationoflongtermuseofdipeptidylpeptidase4inhibitorswiththeriskofdiabeticretinopathyinpatientswithdiabetesmellitusarealworldevidencestudy |