Authors: Marra W, Radboudumc; Tack CJ, Radboudumc; Smits MM, Radboudumc; Contact: Welmoed.Marra@radboudumc.nl

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RA1ra) have demonstrated significant efficacy on cardiovascular outcomes in randomised controlled trials, partly by improving cardiovascular risk factors. However, whether these risk factors also improve in the real-world Dutch clinical practice remains relatively unexplored.

Methods: A retrospective observational cohort study was conducted using electronic health record data at Radboudumc. Clinical data were extracted using CTcue^®. Individuals with T2DM and/or obesity who started a GLP-1RA1ra, sulfonylurea (SU), DPP-4 inhibitor (DPP4i) or SGLT-2 inhibitor (SGLT2i) were identified and included in this analysis. Linear Mixed-effects Models were used to examine changes in cardiovascular risk factors over 12 months, including glycaemic control, body weight, lipid profile, renal function, liver enzymes and blood pressure, including stratification by baseline cardiovascular risk status and evaluation of concomitant medication use.

Results: Among 3,428 patients with T2DM and/or obesity, 721 received GLP-1RA, 899 received SGLT2i, 166 received DPP4i, and 1,634 received SU. The GLP-1RA group showed the largest reductions in HbA_1c (-6.4 mmol/mol) and body weight (-4.9 kg) in 12 months compared to the other antihyperglycemic treatment groups. Changes in systolic blood pressure (-6.0 mmHg), triglycerides (-0.9 mmol/L), and estimated glomerular filtration rate (eGFR) also differed between treatment groups over time. Other cardiovascular risk factors, including lipid parameters, liver enzymes and urinary albumin/creatinine-ratio, showed no meaningful between-group differences. The observed effects on cardiovascular risk factors were largely comparable between patients with very-high and high cardiovascular risk. Starting a GLP-1RA did not lead to significant changes in antihypertensive or lipid-lowering therapy during follow-up compared to other antihyperglycemic medication.

Discussion/Conclusion: In this single-centre real-world study, observed effects were broadly consistent with randomised controlled trials, although effect sizes differed. This likely reflects differences in baseline characteristics and treatment adherence between real-world and trial populations. These findings contribute to the growing body of real-world evidence supporting the use of GLP-1RA in patients with T2DM and/or obesity in routine clinical practice.