Endocrine Abstracts

JOINT782

Background: Metformin, widely used for managing type 2 diabetes, has demonstrated significant benefits in addressing obesity-related metabolic and cardiovascular complications. Its anti-inflammatory, antioxidative, and lipid-modulating properties position it as a potential therapeutic option for reducing obesity-related cardiometabolic risks.

Methods: This review synthesizes evidence from cellular, animal, and clinical studies to explore metformin’s mechanisms of action and its impact on metabolic and cardiovascular parameters in obese patients and adolescents. Key outcomes assessed include inflammation, oxidative stress, lipid profiles, vascular health, and cardioprotective effects.

Results: 1. Mechanisms of Action: Metformin activates AMP-activated protein kinase (AMPK), reducing inflammation and oxidative stress in adipose tissue, the liver, and blood vessels. It decreases pro-inflammatory cytokines (e.g., TNF-α, IL-6) and inhibits the NF-κB pathway, shifting macrophages from pro-inflammatory (M1) to anti-inflammatory (m²) states, thereby lowering metabolic and cardiovascular risks.

2. in vitro Findings: Metformin reduces inflammation, oxidative stress, and vascular smooth muscle cell proliferation in atheroma cells. It stabilizes plaques by enhancing autophagy and reducing reactive oxygen species (ROS) production, lowering the risk of rupture and atherosclerosis-related complications.

3. Animal Studies: In obese animal models, metformin improved endothelial function, reduced systemic inflammation, enhanced lipid metabolism, and demonstrated cardioprotective effects, including reduced myocardial ischemia and infarct size.

4. Clinical Impacts:.

• Blood Pressure and CIMT: Metformin lowered systolic and diastolic blood pressure by improving insulin sensitivity and reducing oxidative stress, also decreasing carotid intimal-medial thickness (CIMT), a marker of early atherosclerosis.

• Atherogenic Index: Metformin improved the ratio of triglycerides to HDL cholesterol, contributing to lower cardiovascular risk in obese patients and adolescents.

• Lipid and Metabolic Effects: It lowered triglycerides, LDL cholesterol, and BMI while increasing HDL cholesterol and insulin sensitivity, with modest improvements in BMI and metabolic markers in adolescents.

Conclusions: Through its multifaceted mechanisms of action, metformin demonstrates significant potential in managing obesity-related metabolic and cardiovascular risks. By improving insulin sensitivity, lipid metabolism, and vascular health while reducing inflammation and oxidative stress, metformin offers a promising strategy for mitigating obesity’s cardiometabolic complications.