A small Vanderbilt Health study suggests empagliflozin may reduce blood-vessel inflammation through immune-cell changes beyond its effects on blood sugar and weight.
A study published in Circulation, the journal of the American Heart Association, suggests that a widely used class of diabetes medicines may do more than lower blood sugar and aid weight loss. Researchers at Vanderbilt Health found that SGLT2 inhibitors, including empagliflozin, were linked to a marked decline in inflammatory immune cells in women with obesity and pre-diabetes, pointing to a possible direct effect on cardiovascular risk beyond metabolism alone.
Mona Mashayekhi, an assistant professor of medicine at Vanderbilt Health who oversaw the work, said earlier hints that these drugs influence the immune system came largely from animal experiments. In this study, she said, the team found direct evidence in humans that empagliflozin appears to shift immune cells into a more stable, less inflammatory state, a result that could help identify which patients stand to benefit most and may open the door to new drug targets.
The researchers treated 16 women with obesity and pre-diabetes for three months, while a comparison group followed a low-calorie diet. Using advanced gene sequencing and cell imaging, they tracked a drop in so-called platelet-monocyte aggregates, clusters formed when clotting cells stick to immune cells and are thought to contribute to blood vessel inflammation. The decline was already visible after two weeks and became stronger by week 12 in the drug group, but not in the diet-only group, which the authors said suggests the cardioprotective effects extend beyond weight loss and may involve metabolic reprogramming of immune cells.
The findings fit with a broader body of research indicating that SGLT2 inhibitors may have anti-inflammatory properties. Reviews indexed on PubMed and meta-analyses in peer-reviewed journals have linked the medicines to reductions in inflammatory markers such as interleukin-6, C-reactive protein and tumour necrosis factor-alpha in animal studies, while human trials have produced more mixed results, including some analyses in which empagliflozin did not clearly outperform placebo on systemic inflammation. Vanderbilt researchers have now begun enrolling patients for a randomised, placebo-controlled study of 74 people with obesity and metabolic syndrome, with the next phase set to examine immune changes and fat tissue to better understand how obesity-related inflammation develops.
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