Why Weight-Loss Injections Work Better for Some People: Genetics May Hold the Answer

Could Your DNA Determine How Well Weight-Loss Drugs Work for You?

Popular weight-loss medications like Wegovy and Mounjaro have transformed obesity treatment worldwide — but not everyone experiences the same results. Now, scientists believe they may have uncovered one piece of that puzzle: your genes.

A new study published in the journal Nature suggests that variations in two specific genes involved in gut hormone pathways may help explain why some patients shed significantly more weight than others when taking glucagon-like peptide 1 (GLP1) medications — and why certain individuals are more prone to side effects.

What Are GLP1 Medications?

GLP1 receptor agonists, which include semaglutide (sold under the brand name Wegovy) and tirzepatide (marketed as Mounjaro), are a class of drugs designed to mimic naturally occurring gut hormones. These medications work by regulating appetite, supporting insulin release, and improving digestion. Millions of people around the globe rely on them as part of their obesity management plans.

Despite their widespread use, doctors and researchers have long been puzzled by the considerable differences in how patients respond — both in terms of weight lost and the side effects experienced.

The Study: Analyzing Nearly 28,000 Patients

Researchers from 23andMe, a nonprofit medical research institute, conducted a large-scale analysis of data from 27,885 patients currently taking GLP1 drugs. Their goal was to determine whether specific genetic markers could be linked to varying outcomes.

The team identified two notable gene variants:

• rs10305420 — a variant in the GLP1 receptor gene that was associated with slightly greater weight loss in those who carried it compared to those who did not.
• rs1800437 — a separate variant linked to increased rates of nausea and vomiting in patients taking tirzepatide, though it showed no significant connection to the amount of weight lost.

These findings point to a potential genetic component in how individuals process and respond to GLP1 therapies.

How Significant Is the Genetic Influence?

While the results are scientifically intriguing, experts are urging caution about overstating their practical significance. The researchers themselves acknowledged that the overall influence of genetics appeared to be relatively modest.

Marie Spreckley, an obesity specialist at the University of Cambridge who was not part of the research team, offered a measured assessment of the findings.

"The magnitude of these genetic effects is small in clinical terms," she explained. "Non-genetic factors such as sex, drug type, dose, and duration appear to explain a substantially larger proportion of variability. The authors' model suggests that most of the explained variance comes from these factors, with genetics adding only a modest incremental contribution."

She further noted that the study reinforces a broader truth about GLP1 therapies: while patient responses do vary considerably, genetics is just one element of a far more intricate picture.

"Behavioural, clinical, and treatment-related factors remain the dominant drivers of outcomes," Spreckley added.

What This Means for the Future of Obesity Treatment

Despite the modest effect size, researchers believe this study represents an important step toward more personalized obesity care. Understanding how genetic differences influence drug response could eventually support precision medicine approaches — where treatment decisions are tailored to an individual's biological profile.

However, experts agree that the evidence is not yet strong enough to incorporate genetic testing into routine clinical practice when prescribing weight-loss medications.

"This is an important step toward understanding variability and the potential for future precision approaches," Spreckley said, "but the effects are modest and the evidence is not yet sufficient to support using genetic information to guide treatment decisions in routine clinical practice."

The Bottom Line

Genetics may play a role in how your body responds to weight-loss injections — but it is far from the whole story. Lifestyle factors, the specific medication used, dosage, and treatment duration all appear to have a far greater bearing on outcomes. As research in this area continues to evolve, a more complete and nuanced understanding of obesity treatment is gradually taking shape.