Statins aggravate insulin resistance through reduced blood glucagon-like peptide-1 levels in a microbiota-dependent manner

Cell Metab. 2024 Feb 6;36(2):408-421.e5. doi: 10.1016/j.cmet.2023.12.027.


Statins are currently the most common cholesterol-lowering drug, but the underlying mechanism of statin-induced hyperglycemia is unclear. To investigate whether the gut microbiome and its metabolites contribute to statin-associated glucose intolerance, we recruited 30 patients with atorvastatin and 10 controls, followed up for 16 weeks, and found a decreased abundance of the genus Clostridium in feces and altered serum and fecal bile acid profiles among patients with atorvastatin therapy. Animal experiments validated that statin could induce glucose intolerance, and transplantation of Clostridium sp. and supplementation of ursodeoxycholic acid (UDCA) could ameliorate statin-induced glucose intolerance. Furthermore, oral UDCA administration in humans alleviated the glucose intolerance without impairing the lipid-lowering effect. Our study demonstrated that the statin-induced hyperglycemic effect was attributed to the Clostridium sp.-bile acids axis and provided important insights into adjuvant therapy of UDCA to lower the adverse risk of statin therapy.

Keywords: Clostridium; GLP-1; UDCA; glucose intolerance; statin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atorvastatin / pharmacology
  • Atorvastatin / therapeutic use
  • Bile Acids and Salts
  • Glucagon-Like Peptide 1
  • Glucose Intolerance* / drug therapy
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Insulin Resistance*
  • Microbiota*
  • Ursodeoxycholic Acid / pharmacology
  • Ursodeoxycholic Acid / therapeutic use


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Atorvastatin
  • Glucagon-Like Peptide 1
  • Bile Acids and Salts
  • Ursodeoxycholic Acid