GLP-1-based therapies to boost autophagy in cardiometabolic patients: From experimental evidence to clinical trials

Area of Science:

• Metabolic and Cardiovascular Research
• Cellular Homeostasis and Disease Mechanisms

Background:

• Obesity significantly impacts cardiovascular health through metabolic dysregulation, inflammation, and oxidative stress.
• Existing obesity therapies like caloric restriction and bariatric surgery have limited long-term efficacy, necessitating novel strategies.
• Autophagy, a cellular degradation process, is crucial for maintaining homeostasis and is implicated in metabolic disorders such as obesity and atherosclerosis.

Purpose of the Study:

• To review the role of autophagy in obesity pathophysiology.
• To explore the potential of autophagy modulators, specifically Dipeptidyl Peptidase-4 (DPP-4) inhibitors and Glucagon-Like Peptide-1 (GLP-1) receptor agonists, in treating obesity and its vascular complications.

Main Methods:

• Literature review of preclinical and clinical studies on autophagy in obesity.
• Critical analysis of experimental evidence for GLP-1-based therapies.
• Discussion of recent clinical trial data for DPP-4 inhibitors and GLP-1 receptor agonists regarding autophagy modulation.

Main Results:

• Defects in autophagy are linked to obesity, insulin resistance, diabetes, and atherosclerosis.
• GLP-1-based therapies may positively influence autophagy in perivascular adipose tissue, potentially improving endothelial dysfunction.
• Preclinical data suggest autophagy modulators are promising, but clinical efficacy requires further validation.

Conclusions:

• Understanding autophagy's role in obesity is vital for developing new therapeutic strategies against vascular complications.
• DPP-4 inhibitors and GLP-1 receptor agonists represent a promising class of drugs that may modulate autophagy for obesity treatment.
• Further clinical investigation is needed to confirm the therapeutic benefits of pharmacological autophagy modulation in obese patients.