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. 2025 Mar;87(3):951-958.
doi: 10.1007/s12020-024-04085-8. Epub 2024 Nov 9.

Adiponectin may play a crucial role in the metabolic effects of GLP-1RAs treatment in patients with Type 2 Diabetes Mellitus: a preliminary longitudinal study

Antonella Al Refaie  1   2 , Leonardo Baldassini  1 , Caterina Mondillo  1 , Elena Ceccarelli  1 , Roberto Tarquini  2 , Luigi Gennari  1 , Stefano Gonnelli  1 , Carla Caffarelli  3
Affiliations

Adiponectin may play a crucial role in the metabolic effects of GLP-1RAs treatment in patients with Type 2 Diabetes Mellitus: a preliminary longitudinal study

Antonella Al Refaie et al. Endocrine. 2025 Mar.

Abstract

Purpose: Type 2 diabetes mellitus (T2DM) stands as the most prevalent metabolic disorder globally. T2DM entails numerous cardiovascular complications, which contribute significantly to morbidity, mortality, and increased public spending worldwide. The real challenge for new diabetes drugs lies not only in reducing blood glucose levels and glycated hemoglobin but also in preventing cardiovascular risk. Emerging receptor agonists for glucagon-like peptide-1 (GLP-1RAs) have demonstrated a pivotal role in diabetes management and mitigating cardiovascular risk.

Methods: We conducted a 12-month longitudinal investigation evaluating the cardio-metabolic effects of GLP-1RAs on a cohort of 65 Caucasian patients diagnosed with T2DM who were scheduled for treatment with GLP-1RAs. Fifty-four T2DM patients successfully completed the 12-month study period, with 30 receiving dulaglutide and 24 receiving semaglutide.

Results: In our study population, GLP-1RAs resulted in several positive changes beyond the observed weight loss: a shift in fat distribution, indicated by a reduction in the percentage of visceral fat (1.21 vs. 1.17, p < 0.05); a significant decrease in LDL cholesterol levels (p < 0.05) and triglycerides (p < 0.01); and a significant increase in serum adiponectin levels (p < 0.05), potentially indicating a reduction in insulin resistance and inflammation. Additionally, we observed a significant decrease in microalbuminuria and media-intimal thickness at the carotid vessel level (p < 0.05).

Conclusions: In patients with T2DM 1-year therapy with GLP-1RAs has a positive effect on the main determinants of cardiovascular risk including body weight, visceral fat, dyslipidemia, and atherosclerosis. Moreover, the increase in adiponectin may play a pivotal role in controlling the inflammatory state and the mechanisms of vascular damage.

Keywords: Adiponectin; Atherosclerosis; Body Composition; GLP1-RAs (Dulaglutide, Semaglutide); Lipids; Type 2 Diabetes Mellitus (T2DM).

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Conflict of interest statement

Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. Ethics approval and consent to participate: The study was performed in line with the principles of the 1964 Helsinki Declaration and its later amendments. Institutional Review Board approval was obtained for the study protocol (ID 14783/19). All the study patients gave their written informed consent to participate in the study.

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