How do incretins, such as Glucagon-like peptide-1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP), reduce inflammation?

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From the Guidelines

Incretins, specifically GLP-1 receptor agonists, reduce inflammation through multiple mechanisms, including inhibition of pro-inflammatory cytokines and modulation of immune cell function, as demonstrated in the most recent and highest quality study by 1. The anti-inflammatory effects of GLP-1 receptor agonists, such as liraglutide, semaglutide, and exenatide, have been shown to decrease markers of inflammation, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), in patients with type 2 diabetes and other inflammatory conditions. Some key points about the anti-inflammatory effects of incretins include:

  • The anti-inflammatory effects occur through direct activation of GLP-1 receptors on immune cells and indirect effects via improved glycemic control and weight reduction.
  • Typical therapeutic doses of GLP-1 receptor agonists have shown these anti-inflammatory benefits within 3-6 months of treatment.
  • DPP-4 inhibitors, such as sitagliptin and saxagliptin, also demonstrate modest anti-inflammatory effects by increasing endogenous incretin levels.
  • The most recent study 1 highlights the benefits of GLP-1 receptor agonists in reducing albuminuria and slowing eGFR decline, which may contribute to their cardiovascular and renal protective effects.
  • The study also notes that GLP-1 receptor agonists, such as liraglutide, semaglutide, and dulaglutide, are preferred agents due to their demonstrated cardiovascular and CKD benefits. Overall, the evidence suggests that incretins, particularly GLP-1 receptor agonists, have anti-inflammatory properties that may contribute to their therapeutic benefits in patients with type 2 diabetes and other inflammatory conditions, as supported by the most recent and highest quality study 1.

From the Research

Incretins and Inflammation Reduction

  • Incretins, such as GLP-1 receptor agonists, have been shown to have anti-inflammatory effects 2.
  • These effects are thought to be mediated by the reduction of neuroinflammation, promotion of nerve growth, and improvement of heart function 2.
  • GLP-1 receptor agonists have also been found to have cardiovascular protective effects, which may be related to their anti-inflammatory properties 3, 4.

Studies Demonstrating Inflammation Reduction

  • A study published in 2021 found that GLP-1 receptor agonists have multiple biological effects, including reducing neuroinflammation and promoting nerve growth 2.
  • Another study published in 2022 found that semaglutide, a GLP-1 receptor agonist, has cardiovascular benefits and can reduce various CV risk factors in patients with established CV disorders 4.
  • A pooled analysis of two trials found that semaglutide and liraglutide, both GLP-1 receptor agonists, had kidney-protective effects in patients with type 2 diabetes, which may be related to their anti-inflammatory properties 5.

Mechanisms of Action

  • GLP-1 receptor agonists work by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion, decelerating gastric emptying, and reducing calorie intake and body weight 3.
  • They also have effects on the nervous, cardiovascular, and endocrine systems, and may have anti-tumorigenic effects 2, 6.
  • The exact mechanisms by which GLP-1 receptor agonists reduce inflammation are not fully understood, but may involve the reduction of pro-inflammatory cytokines and the promotion of anti-inflammatory pathways 2.

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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