WEB DESK: New research suggests that a person’s genetic makeup could influence how well they respond to popular GLP-1 weight-loss medications and whether they experience side effects.
A large study conducted by 23andMe involving nearly 28,000 users found that variations in specific genes can slightly impact the effectiveness of these drugs. The findings, published in Nature, highlight the growing role of genetics in personalized medicine.
Researchers identified a mutation in the GLP1R gene the target of GLP-1 drugs that was linked to modestly improved weight loss. Individuals with one copy of the variant lost about 1.7 pounds more over several months, while those with two copies lost roughly 3.3 pounds more compared to non-carriers.
However, genetic differences may also increase the likelihood of side effects. Variants in both GLP1R and the GIPR gene were associated with nausea and vomiting. Notably, the GIPR-related risk was seen only in patients using tirzepatide marketed as Mounjaro for diabetes and Zepbound for weight loss where carriers were significantly more likely to experience vomiting.
Although the genetic impact on weight loss appears relatively small, scientists say the findings could help pave the way for more tailored obesity treatments in the future.
Heart Benefits May Be Independent of Weight Loss
In a separate study, researchers found that the cardiovascular benefits of GLP-1 drugs may not be directly tied to how much weight a patient loses. Instead, higher doses of medications like semaglutide sold as Ozempic and Wegovy were linked to reduced risks of death, heart attack, stroke, and other heart-related conditions.
The study, involving over 47,000 patients with cardiovascular disease, found that these protective effects persisted even after treatment stopped and were not dependent on the amount of weight lost.
Scientists also discovered that GLP-1 receptors are present not only in the pancreas but also in the heart, raising the possibility that these drugs may directly benefit heart function.
Single DNA Change Can Trigger Sex Reversal
In another breakthrough, researchers demonstrated that a tiny mutation in non-coding DNA regions that regulate gene activity can dramatically alter development.
Using CRISPR technology, scientists introduced a single change in a regulatory DNA segment called Enh13 in mouse embryos. This activated the Sox9 gene, which drives male development, causing genetically female (XX) mice to develop male characteristics.
The study, published in Nature Communications, underscores the powerful role of non-coding DNA, which makes up about 98% of the human genome.
Experts say the findings could improve understanding of conditions known as Differences of Sex Development (DSDs), many of which currently lack a clear genetic explanation.
Overall, the research highlights how even small genetic variations whether in drug-response genes or regulatory DNA can have significant effects on health, treatment outcomes, and human development.
