We’ve known for a while now that metformin doesn’t act primarily in the liver or mitochondria as was once believed. Instead, it concentrates in the gut, where it activates a cellular stress response. Now, two new studies show exactly how this local response ripples outward to benefit metabolism. 🧪
🔬 Study #1 (Lancet eBioMedicine, July 2025): Longitudinal plasma proteomics in ~100 humans before and after met revealed 23 consistently altered proteins. Top hits are signatures of the enteroendocrine cells that produce GLP-1 and GIP, reinforcing that these are the key cellular targets. 🧪
🧬 Study #2 (Diabetes, July 2025): In high-fat-fed rats, met restored lipid sensing in the upper intestine, triggering release of the gut hormone GIP. • A chronic high-fat diet blocks GIP secretion in response to feeding. Metformin relieves this blockage, restoring nutrient sensing and satiety. 🧪
🧩 Together, these studies reinforce a clear effect on the gut–brain axis: metformin activates AMPK in enteroendocrine cells, restoring their ability to sense nutrient status and secrete hormones that shift metabolism in a positive direction. 🧪
In other words, metformin isn't just a glucose-lowering drug—it's a top-down rewiring agent for gut nutrient sensing and hormone modulation, which likely underlies the benefits observed across so many organ systems. 🧪
As a Christian I am amazed at how the body works and functions seamlessly together when it is not in disease . “ I am fearfully and wonderfully made “ “Wonderful are Thy Works and my soul knows it very well ! “
Thank you for sharing this. I've been taking this and I knew nothing about it aside from some reduction in appetite.