Early worsening of diabetic retinopathy in individuals with type 2 diabetes treated with tirzepatide: a real-world cohort study.

IF 10.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia Pub Date : 2025-07-10 DOI:10.1007/s00125-025-06466-8

Adam J Buckley,Garry D Tan,Marta Gruszka-Goh,Peter H Scanlon,Imran Ansari,Sara G I Suliman

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Abstract

AIMS/HYPOTHESIS Early worsening of diabetic retinopathy (EWDR) has been described during treatment with glucagon-like peptide-1 receptor agonists including subcutaneous semaglutide. Whether EWDR occurs after initiating treatment with the potent glucagon-like peptide 1 / gastric inhibitory polypeptide receptor agonist tirzepatide is unknown. METHODS In this retrospective cohort study using real-world clinical data, we matched 3435 tirzepatide-exposed (≥180 days treatment) individuals with type 2 diabetes 1:1 with 3434 tirzepatide-unexposed individuals for sex, diabetes duration, retinopathy status, HbA1c, number of retinal screening episodes and use of glucose-lowering medications. New-onset diabetic retinopathy and retinopathy progression were explored using conditional logistic regression. RESULTS Individuals included in the study had tight baseline glycaemic control (mean HbA1c 56.1 ± 15.8 mmol/mol [7.28 ± 1.43%]). New-onset proliferative diabetic retinopathy (PDR) (grade R3M0, R3M1) occurred in 1.1% of tirzepatide-exposed (n=33) and 0.5% of tirzepatide-unexposed (n=17) individuals. Tirzepatide was significantly associated with new-onset PDR in multivariate analysis after adjustment for established risk factors (OR 2.15 [95% CI 1.24, 3.74], p<0.01). However, tirzepatide was also associated with reduced odds of new onset of retinopathy (OR 0.73 [95% CI 0.62, 0.86], p<0.001) in individuals without diabetic retinopathy (R0M0) at initiation in multivariate analysis, and was not significantly associated with retinopathy progression in individuals with mild non-proliferative diabetic retinopathy (NPDR, grade R1M0 or R1M1). CONCLUSIONS/INTERPRETATION Tirzepatide therapy resulted in significantly increased odds of incident PDR, particularly in individuals with mild NPDR with maculopathy (grade R1M1), or moderate-to-severe NPDR with or without maculopathy (grade R2M0, R2M1). The increase in odds of progression would justify specialist ophthalmologist referral by Early Treatment Diabetic Retinopathy Study (ETDRS) criteria.

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替西肽治疗2型糖尿病患者糖尿病视网膜病变早期恶化：一项真实世界队列研究

目的/假设在使用胰高血糖素样肽-1受体激动剂（包括皮下semaglutide）治疗期间，糖尿病视网膜病变（EWDR）的早期恶化已被描述。在开始使用强效胰高血糖素样肽1 /胃抑制性多肽受体激动剂替西肽治疗后是否发生EWDR尚不清楚。方法在这项使用真实世界临床数据的回顾性队列研究中，我们将3435名接受替西肽治疗（≥180天）的2型糖尿病患者与3434名未接受替西肽治疗的患者在性别、糖尿病病程、视网膜病变状况、HbA1c、视网膜筛查次数和降糖药物使用方面进行了1:1的匹配。采用条件logistic回归对新发糖尿病视网膜病变及其进展进行分析。结果纳入研究的个体基线血糖控制良好（平均HbA1c为56.1±15.8 mmol/mol[7.28±1.43%]）。新发增生性糖尿病视网膜病变（PDR）（R3M0级，R3M1级）发生在1.1%的替西肽暴露者（n=33）和0.5%的未暴露者（n=17）中。在确定危险因素调整后的多因素分析中，替西帕肽与新发PDR显著相关（OR 2.15 [95% CI 1.24, 3.74], p<0.01）。然而，在多变量分析中，替西帕肽还与起始时无糖尿病视网膜病变（R0M0）的个体新发视网膜病变的几率降低相关（OR 0.73 [95% CI 0.62, 0.86], p<0.001），并且与轻度非增生性糖尿病视网膜病变（NPDR， R1M0或R1M1级）的个体视网膜病变进展无显著相关。结论/解释替西肽治疗导致PDR发生的几率显著增加，特别是在轻度NPDR伴黄斑病变（R1M1级）或中度至重度NPDR伴或不伴黄斑病变（R2M0、R2M1级）的患者中。根据早期治疗糖尿病视网膜病变研究（ETDRS）标准，进展几率的增加将证明专科眼科医生的转诊是合理的。

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来源期刊

Diabetologia 医学-内分泌学与代谢

CiteScore

18.10

自引率

2.40%

发文量

193

审稿时长

1 months

期刊介绍： Diabetologia, the authoritative journal dedicated to diabetes research, holds high visibility through society membership, libraries, and social media. As the official journal of the European Association for the Study of Diabetes, it is ranked in the top quartile of the 2019 JCR Impact Factors in the Endocrinology & Metabolism category. The journal boasts dedicated and expert editorial teams committed to supporting authors throughout the peer review process.