By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
Weight loss injection response: why does it differ from person to person?
How people respond to a weight loss injection is one of the questions that patients and doctors care about most today. GLP-1 drugs such as Ozempic and Wegovy (semaglutide) and Mounjaro (tirzepatide) are changing lives. They reduce appetite, balance blood sugar and lead to major weight loss. Yet alongside the success stories, a more complex reality is emerging: the treatment does not work equally well for everyone.
Some people lose dozens of kilograms within months. Others receive the same drug, at the same dose, and see only a small change. This gap once looked like a mystery. Today, science is starting to explain it, and the answer combines biology, behavior and lifestyle.
Genetics enters the picture: does your DNA decide?
In April 2026, researchers at 23andMe published a large genetic study in the journal Nature. They examined 27,885 people who received a GLP-1 drug and who reported their own weight loss and side effects. The goal was to crack a simple question: why does the same drug work strongly in one person and weakly in another?
The researchers identified a variant in the GLP1R gene, the gene for the receptor that these drugs act on. Each copy of this variant added an average of 0.76 kg to weight loss. In addition, variants in the GLP1R and GIPR genes were linked to nausea and vomiting. The link with GIPR appeared only in people taking tirzepatide, the active ingredient in Mounjaro. The likely explanation is that tirzepatide also acts on GIP receptors.
Weight loss injection response: most of the story is not in your genes
The most important finding is actually how small the genetic effect is. According to expert reactions to the study, most of the differences the model explained came from non-genetic factors. These include sex, the type of drug, the dose and the length of treatment. In other words, genes add only a small detail to the picture.
The study also has important limitations. The data relied on self-reports, and for some participants the reported loss was much higher than in their medical records. Moreover, most participants were women of European ancestry, and the median treatment time was about eight months. For this reason, experts stress that the findings are not yet ready for routine treatment decisions. This is an important shift in thinking: the focus moves from biological destiny to overall care and daily habits.
Who does not respond? The “non-responder” phenomenon
In the clinic, we see this complexity clearly. Some patients respond impressively. By contrast, a sizable group does not reach meaningful weight loss. Professionals call them non-responders, meaning patients who do not respond as expected. For example, in the STEP 1 trial of semaglutide 2.4 mg, 86.4% of participants lost at least 5% of their body weight. That means about 13.6% did not reach this threshold. Others have side effects that make it hard to continue treatment.
The key point is that this is not a personal failure. It is natural biological variation, as in many areas of medicine. A weak response does not reflect a lack of motivation or “doing it wrong.” In such cases, we need to reassess the whole picture, and sometimes run tests to personalize treatment.
Not just how much you lost, but what you lost
Beyond asking whether your weight went down, it is important to ask what that weight was made of. A 2024 scientific review found large differences between studies. In some, lean tissue made up 40% to 60% of the weight lost. In others, it made up about 15% or less. However, lean tissue is not only muscle. It also includes organs, bones and fluids.
Still, muscle matters a great deal. It is a key metabolic organ that affects insulin sensitivity, heart health and independence in older age. When weight loss eats into muscle, a person may look slimmer, yet their metabolic health is not optimal. I discuss this further in my article on preserving muscle mass during GLP-1 treatment.
Weight loss injection response: the three factors that really matter
The data and clinical experience point to factors that are not genetic. The first is nutrition. It is not enough for your appetite to drop. You also need the right food mix, and above all enough protein. This is a challenge, because the drugs reduce the desire to eat, and that is exactly when the body needs protein to preserve muscle.
The second is physical activity. Aerobic exercise supports overall health. However, strength training is the key to keeping muscle during weight loss. Without it, much of the loss may come at the expense of muscle.
The third factor is persistence and personalization. Drug treatment needs precise tailoring, sometimes a dose change and sometimes a switch between drugs. This is a dynamic process, not one-size-fits-all care. I have written separately about the approach of adjusting the dose to reach a target. In this way, a weight loss injection response that looks weak at first can improve over time.
The mind plays a role too: stress and sleep
Beyond the body, mental state also affects treatment success. Chronic stress raises cortisol levels. This hormone promotes fat buildup in the belly and harms muscle. In addition, lack of sleep disrupts hormonal balance and increases hunger. So good obesity care also includes sleep, stress management and emotional support. These are not side issues but an essential part of the process. That is how you build a good, stable response to a weight loss injection.
What happens after you stop the weight loss injection?
Another central question is what happens after treatment stops. In the STEP 1 extension, one year after stopping semaglutide, participants regained about two-thirds of the weight they had lost. Most of the improvement in metabolic measures also returned to baseline. There is also concern that the regained weight may be mostly fat, while lost muscle may not fully come back. This could lead to sarcopenic obesity, meaning excess fat together with too little muscle. You can read more in my article on stopping obesity medications and weight regain.
Pharmacogenetics: the future is on its way
This genetic research is part of a broader trend toward personalized medicine. Pharmacogenetics, the field that studies how genes affect drug response, promises that one day we will choose drugs by genetic profile. Along these lines, 23andMe already includes these findings in a report for its customers. According to the company, its estimates range from 6% to 20% weight loss after one year, and from 5% to 78% risk of nausea and vomiting. Even so, there is currently no recommendation for routine genetic testing before treatment. The road is still long, but the direction is clear.
The bottom line: the drug is only part of the story
Your response to a weight loss injection depends mainly on the combination of the right drug treatment, tailored nutrition, physical activity, emotional balance and persistence. Genetics can influence the journey, but it does not set the destination. Ultimately, the goal is not just a lower number on the scale. The goal is health, daily function and quality of life for years to come. Not a quick fix, but a process. Not magic, but medicine. If you would like to discuss your own treatment, you are welcome to contact my clinic.
The information in this article is general and does not replace personal medical advice.
References
Genetic predictors of GLP1 receptor agonist weight loss and side effects
Unlocking the Genetics of GLP-1 Medications: Why Your DNA Matters
Once-Weekly Semaglutide in Adults with Overweight or Obesity
Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies
Researchers at 23andMe conducted the genetic study. Novo Nordisk funded the STEP 1 trials.
