Enzyme That Breaks Down GLP-1 Identified, Offering Path to Longer-Lasting Diabetes and Obesity Drugs

Chinese researchers have identified a new enzyme that breaks down GLP-1, a key component of diabetes and obesity treatments, and developed modified drugs that block this process and prolong the drugs’ effects.

A research team led by Zhang Yaoyang and Shan Bing at the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, published the findings in the international journal Science Advances on Aug. 26, 2026.

The researchers were the first to identify insulin-degrading enzyme (IDE) as an enzyme that breaks down GLP-1. IDE was found to cleave GLP-1 at two sites, reducing its ability to regulate blood glucose.

GLP-1 is a hormone that stimulates insulin secretion and suppresses appetite, and it is a key target for diabetes and obesity treatments. However, it is rapidly broken down by enzymes in the body, giving it a short half-life.

The researchers modified GLP-1 and semaglutide by substituting D-amino acids at IDE cleavage sites. The modified peptides were found to be more resistant to degradation in plasma and in the liver, intestines, ascites and central nervous system.

In particular, D-Ser18-semaglutide had a longer duration in the bloodstream and sustained its blood glucose-lowering effect in mouse experiments. The researchers said, “A single D-amino acid substitution enabled better blood glucose control even with fewer doses.”

In an experiment in which the drug was injected directly into the hypothalamus of obese mice, it produced greater weight loss than conventional semaglutide. The researchers said IDE plays a particularly important role in GLP-1 degradation in the central nervous system.

The researchers said the findings offer a new mechanism for regulating GLP-1 metabolism and lay the groundwork for designing next-generation, long-acting GLP-1 receptor agonists with improved efficacy for treating metabolic and central nervous system disorders.