Comparative Effects of Dulaglutide and Semaglutide on Renal Function Decline and Proteinuria Reduction in Diabetic Patients: A Retrospective Cohort Study

<b>Background:</b> GLP-1 receptor agonists (GLP-1 RAs) lower glucose and reduce cardiovascular events in type 2 diabetes, with noted renal benefits. Few studies directly compare GLP-1 RAs. This study aims to compare the effects of semaglutide and dulaglutide on renal function decline and proteinuria reduction in diabetic patients. <b>Methods:</b> The present study was conducted at Wanfang Hospital, Taipei Medical University. Diabetic patients using either semaglutide or dulaglutide for more than 1 year in the outpatient department from 1 January 2022 to 30 September 2024 were enrolled retrospectively. The outcome events in the present study included a decline in the estimated glomerular filtration rate (eGFR), an increase in the urine albumin-creatinine ratio (UACR), and patient death. <b>Results:</b> A total of 268 patients on dulaglutide and 747 on semaglutide were included. Baseline eGFR levels were similar in both groups. After 12 months, eGFR levels did not significantly decline in both groups. However, the dulaglutide group showed significantly higher UACR increases than the semaglutide group (<i>p</i> < 0.01). More death events also occurred in the dulaglutide group (<i>p</i> < 0.01). Multivariate logistic regression revealed a higher risk of UACR increase with dulaglutide (<i>p</i> < 0.01). Subgroup analysis found dulaglutide associated with higher UACR in patients younger than 60, males, those with hypertension, without heart failure, those using angiotensin receptor blockers, biguanides, and statins, and those not using sodium-glucose cotransporter-2 inhibitors. <b>Conclusions:</b> Dulaglutide and semaglutide had comparable effects on slowing eGFR decline. However, dulaglutide was less effective in reducing UACR, particularly in the subgroups mentioned above.