People with diabetes and obesity have altered gut microbiomes, with more detrimental Firmicutes at the expense of beneficial Bacteroidetes^1,2. Firmicutes are proinflammatory, promote harvesting and storage of fat and can cause glucose intolerance³. It is now recognised that the microbiome is a significant contender in the pathogenesis of many chronic diseases, including metabolic ones like diabetes⁴.

People who undergo gastric bypass surgery often experience significant metabolic changes which cannot be attributed to weight loss alone⁵. Recent research into this puzzling phenomenon suggests these patients develop a more diverse microbiome, which could help explain the dramatic improvements in glucose and lipid metabolism.

As a pharmacist, Metformin would have to be my favourite drug and it keeps on delivering. It has stood the test of time and, despite promising new drugs on the market, remains first line for type 2 diabetes⁶. It has a proven track record and is safe and well-tolerated by most patients. The funny thing is, despite being so widely prescribed for over 50 years, its mechanism of action has remained relatively unclear. Recent findings have revealed its long-kept secret.

The bioavailability of Metformin is about 50%, which means, when taken orally, only half the drug actually reaches the systemic circulation⁷. The remaining 50% concentrates in the gut mucosa at concentrations 30 to 300 times greater than in the plasma⁸. Moreover, when given intraveneously, it is not particularly effective at reducing blood sugar levels⁹. A recent study found that, when a delayed release oral metformin dose was given – so that the medication was released only when it reached the lower part of the gastrointestinal tract – it was more effective at lowering blood sugar levels than conventional tablets, despite lower plasma concentrations¹⁰.

Researchers then hypothesised that if Metformin’s mechanism of action resides in the gut, perhaps it is due to alterations in the gut microbiome. This is exactly what they found: metformin does in fact shift the gut microbiota, promoting more beneficial microbes¹¹. These beneficial microbes produce anti-inflammatory short chain fatty acids (SCFA) and promote the integrity of the gut lining, which explains part of its glucose lowering and anti-inflammatory effects¹².

To prove cause and effect, researchers transferred a faecal transplant from individuals treated with metformin into germ-free mice (no microbiomes) and found that two out of three recipients showed improved glucose tolerance¹³. This further supports the notion that Metformin’s glucose-lowering effect is partly due to its microbiome-altering properties.

Armed with this insight into Metformin’s anti-inflammatory and pleiotropic effects, researchers are now studying its effectiveness in a range of conditions, including cardiovascular disease, cancer and aging, with promising results^14,15,16. What we should really take away from this research is the power of the microbiome!

We know that diet and lifestyle are pivotal for a healthy, blossoming microbiome and, combined, can be more powerful than any drug. A recent study demonstrated how dietary fibre increased the relative abundance of SCFA producing microbiota which resulted in reduced HbA1c¹⁷. The greater the variety and abundance of these SCFA producing microbes, the greater the reduction in HbA1c.

Educating patients about the tiny life-forms that reside in our gut can be both eye-opening and empowering. When they learn that these microbes are at the mercy of our lifestyle habits and behaviours, many feel a sense of control and optimism. For me, this is another tool in my toolbox for provoking informed behaviour change.