To put it simply: the research is still at its very early stage. Most of the findings come from lab studies of human pancreatic tissue and mice models. For example, the Duke study found evidence of higher-than-expected GLP-1 production in alpha cells from human samples.
Apart from that, a biotech company, Fractyl Health, is developing a gene-therapy style approach (called “Rejuva”) that uses a viral vector to deliver DNA instructions to pancreatic cells so they produce GLP-1 themselves — and in mouse models, they reportedly achieved ~20% weight loss in three weeks. What’s more? Normal-weight mice also didn’t gain any weight and maintained healthy blood sugar levels after being treated and given a high-fat diet.
Fractyl Health cofounder and CEO Harith Rajagopalan told CNN, “It outperformed semaglutide.”
The approach works by using a small virus that can insert DNA instructions on how to produce GLP‑1 into cells.
Rajagopalan explained, “Because we are delivering it locally, we believe that we will need a very low dose of this virus, which helps gives us confidence in the potential safety in people.”
However, experts warn that such an approach in humans would likely be irreversible and could lead to long-term issues in the pancreas, which is responsible for blood sugar control.
On the other hand, Fractyl competitor RenBio used a different approach, by including the DNA instructions to make GLP-1 in a saline solution, which is then injected into muscle tissue. Short electrical pulses then allow the instructions to be delivered directly into cells, effectively “using the cell’s own machinery to turn it into a protein factory,” as per CNN.
Mice injected with the solution lost roughly 15% of their body weight, significantly more than mice in a placebo group, and kept the weight off for at least a year. Blood sugar level regulation improved as well.