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Hypoglycemic drugs, circulating inflammatory proteins, and gallbladder diseases: A mediation mendelian randomization

Zi-Qi Wang1, Jin-Yan Zhang1, Xingyao Tang2

  • 1Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Diabetes Research and Clinical Practice
|October 4, 2024
PubMed
Abstract

Insights

Metformin may protect against gallstones by influencing specific gene pathways, while GLP-1 receptor agonists might increase the risk of gallbladder inflammation. These findings suggest potential links between diabetes medications and gallbladder health.

Area of Science:

  • Endocrinology and Metabolism
  • Gastroenterology
  • Pharmacogenomics

Background:

  • The interplay between hypoglycemic drugs, inflammatory markers, and gallbladder diseases is not well understood.
  • Investigating these relationships is crucial for patient safety and treatment optimization.

Purpose of the Study:

  • To investigate the causal associations between four classes of hypoglycemic drugs and two common gallbladder diseases: cholecystitis and cholelithiasis.
  • To explore potential mediating pathways for observed drug-disease associations.

Main Methods:

  • A Mendelian Randomization (MR) study design was utilized.
  • Exposure variables included glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and metformin.
  • Outcome variables were cholecystitis and cholelithiasis.

Main Results:

  • Dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter 2 inhibitors (SGLT-2i) showed no significant association with either gallbladder disease.
  • Metformin demonstrated a protective association with cholelithiasis (gallstones), potentially mediated by Interleukin-10 receptor subunit beta (IL-10RB) and Neurotrophin-3 (NT-3) pathways.
  • Glucagon-like peptide-1 receptor agonists (GLP-1RA) were associated with an increased risk of cholecystitis (gallbladder inflammation).

Conclusions:

  • Metformin appears to have a protective effect against gallstones, possibly through modulation of NT-3 and IL-10RB.
  • GLP-1 receptor agonists may be associated with a higher risk of gallbladder inflammation.
  • Further research is warranted to validate these findings and elucidate the underlying mechanisms.
Keywords:
CholecystitisCholelithiasisGlucagon-like peptide-1 receptor agonistsHypoglycemic drugsInflammatory proteinsMendelian RandomizationMetformin

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