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HMGCR and Rosuvastatin Regulates GLP-1 Secretion and Expression-A Translational Study
Michael G Miskelly1, Andreas Lindqvist1, Amra Jujić2
1Neuroendocrine Cell Biology, Department of Experimental Medical Science, Lund University, Malmö 21428, Sweden.
The Journal of Clinical Endocrinology and Metabolism
|November 8, 2025
Summary
Statins like rosuvastatin may impact blood sugar by affecting glucagon-like peptide-1 (GLP-1) secretion. This study found HMGCR inhibition reduces GLP-1, potentially explaining statin-induced hyperglycemia.
Area of Science:
- Endocrinology
- Metabolic disease research
- Pharmacology
Background:
- Statin use is linked to increased type 2 diabetes risk and mild hyperglycemia.
- Mechanisms underlying statin-associated glucose intolerance are not fully understood.
- The impact of statins on glucagon-like peptide-1 (GLP-1) secretion remains unclear.
Purpose of the Study:
- To investigate the effects of rosuvastatin on GLP-1 secretion and production.
- To explore the role of HMGCR in regulating GLP-1.
Main Methods:
- Human association studies in the Malmö Diet and Cancer Study.
- In vitro experiments using GLUTag cells.
- Acute and chronic studies in C57Bl/6j mice.
Main Results:
- In non-diabetic individuals, statin use correlated with higher GIP, insulin, glucose, glucagon, and HOMA-IR, but not GLP-1.
- In type 2 diabetes patients, statin use was linked to higher fasting GLP-1.
- Rosuvastatin and HMGCR knockdown reduced GLP-1 secretion and increased Gcg mRNA in GLUTag cells.
- Acute rosuvastatin reduced postprandial GLP-1; chronic treatment in mice caused hyperglycemia and increased postprandial GLP-1.
- HMGCR inhibition's effect on GLP-1 was mimicked by PCSK9 inhibitor, suggesting a cholesterol-dependent pathway.
Conclusions:
- HMGCR is identified as a regulator of GLP-1 secretion.
- This provides a potential mechanism for statin-associated mild hyperglycemia.
- Monitoring blood glucose is advised when prescribing rosuvastatin due to its acute negative effect on GLP-1 secretion.
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