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
GLP-1 dose increase: treat to target, not to the maximum dose
A GLP-1 dose increase usually follows a fixed, step-by-step schedule. We have grown used to thinking about semaglutide and tirzepatide treatment as this kind of path: start low, wait a few weeks, step up and continue to the maintenance dose. But what happens when a patient already responds well to the starting dose? Hunger has eased, fullness has improved, the weight is coming down and the patient feels great. Is there still a benefit to increasing the dose?
A new study, published on August 31, 2026, in the Oxford University Press journal Biology Methods and Protocols, raises an interesting question. For some patients, perhaps we should ask less about “which dose they need to reach.” Instead, we should ask “which dose achieves the goal for this particular patient.”
What happens to patients who stay on the starting dose?
The researchers analyzed electronic medical records from a US database of about 29 million patients. Of 490,072 people who received semaglutide, 814 met the criterion of long-term treatment at only 0.25 mg. Similarly, of 322,442 people who received tirzepatide, 1,016 stayed at only 2.5 mg over time.
The definition was relatively strict: at least three separate prescriptions for the same dose, over at least six months. For the direct comparison, the researchers matched 534 patients in each group by age, sex, starting body mass index (BMI) and type 2 diabetes.
It is important to be precise here. The researchers used prescription patterns as a stand-in for proof of ongoing use. In other words, they could see that patients repeatedly received prescriptions for the low dose. However, they cannot know for certain whether patients filled them or how they actually used the drug.
The starting dose also led to weight loss
After 12 months, patients who stayed on tirzepatide 2.5 mg lost an average of about 5.5% of their body weight. By contrast, those who stayed on semaglutide 0.25 mg lost an average of about 2.2%. In addition, the researchers looked at side effects over 24 months. After statistical correction for multiple comparisons, no difference between the two drugs remained significant.
These results are far more modest than those we see at maintenance doses. For example, in the STEP 1 trial, semaglutide 2.4 mg led to 14.9% weight loss after 68 weeks, compared with 2.4% on placebo. In the SURMOUNT-1 trial, tirzepatide led to weight loss of 15.0%, 19.5% and 20.9% at doses of 5, 10 and 15 mg, after 72 weeks.
So the message of the study is not that a low dose works as well as a high dose. Rather, the interesting message is different: even starting doses give some patients meaningful clinical activity over time.
High doses and the GLP-1 dose increase: what we know today
Over the past year, the dose range has actually expanded upward. In March 2026, the US Food and Drug Administration (FDA) approved Wegovy at a dose of 7.2 mg. The STEP UP trial showed that this dose led to an average weight loss of 20.7% after 72 weeks among patients who stayed on treatment. Meanwhile, in the SURMOUNT-5 trial, tirzepatide at the maximum tolerated dose led to 20.2% weight loss, compared with 13.7% with semaglutide.
In other words, patients who need it now have especially powerful options. I compare two of them in my article on Mounjaro vs. Wegovy. Still, the availability of a high dose doesn’t mean every patient must reach it.
A starting dose is not necessarily microdosing
In public discussion, the term “microdosing,” meaning the use of tiny doses, has become very popular. However, it is important to separate it from what this study examined. The researchers looked at approved starting doses: 0.25 mg of semaglutide and 2.5 mg of tirzepatide. They did not test tiny doses or partial doses under a dedicated protocol.
The researchers themselves note that this pattern may overlap with intentional microdosing in some patients. Yet the study cannot determine that. In addition, the FDA warns about dosing errors with unapproved compounded products. Therefore, any change in dose should go through your treating doctor, using an approved medication.
Why do patients skip a GLP-1 dose increase?
Real life differs from a clinical trial. Patients may stay on a low dose for many reasons. For example, they may respond well early on, want to limit side effects, or face issues of cost, drug availability or a personal treatment goal. The study does not reveal each patient’s reason. However, it does show that this happens in the real world, and that is exactly what makes it clinically interesting.
A GLP-1 dose increase based on the target: treat to target
In medicine, we know the “treat to target” principle well. Perhaps it is time to apply the same thinking to titration, that is, to the timing of each GLP-1 dose increase. Our goal is not to reach a particular number on the injection pen. Instead, the goal is a good clinical response: hunger control, fullness, sufficient weight loss, better metabolic markers and quality of life, together with good tolerance.
For a patient who responds well to a low dose, then, we can ask whether there is any need to rush the next step just because the schedule says so. On the other hand, when hunger returns, weight loss stalls before the goal, or the metabolic response is insufficient, a higher dose can help unlock the full potential of treatment.
This leads to a slightly different mindset: not “titrate to maximum,” but “treat to target.” In other words, the aim is to find the lowest dose that delivers a good, lasting clinical response. It is not to reach, automatically, the highest dose the patient can tolerate.
What the study does not yet prove
It is important to stress that the study does not prove this is the better treatment strategy. This is an observational study of real-world data, not a randomized trial comparing personalized titration with standard titration. In addition, according to the drug labels, starting doses are meant mainly to help the body adjust. That is why the decision on a GLP-1 dose increase remains a personal medical decision. You may also want to read about the side effects of GLP-1 medications and how obesity medications work.
A question for discussion
A patient is taking 2.5 mg of tirzepatide or 0.25 mg of semaglutide. Their weight is coming down nicely, hunger is under control, tolerance is excellent and they are satisfied. Do we keep stepping up according to the standard schedule, or leave them on the low dose as long as the response is good? And what defines the target: the pace of weight loss, the percentage lost, hunger control, waist circumference and metabolic markers, or a combination of all of these?
The bottom line on a GLP-1 dose increase
Ultimately, the important question at the next visit is not “Which dose have you reached?” Instead, it is “Is the current dose still doing the job?” The dose of tirzepatide or semaglutide should serve the patient’s goal, not the other way around.
The information in this article is general and does not replace personal medical advice.
References
Once-Weekly Semaglutide in Adults with Overweight or Obesity
Tirzepatide Once Weekly for the Treatment of Obesity
Tirzepatide as Compared with Semaglutide for the Treatment of Obesity
Wegovy HD (semaglutide 7.2 mg) approved in the US, providing 20.7% mean weight loss
FDA’s Concerns with Unapproved GLP-1 Drugs Used for Weight Loss
Disclosure: the study’s authors are employees of nference, a company that has research collaborations with manufacturers of the drugs included in the study. According to the authors, the study received no external funding.
