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When GLP-1 weight loss slows or stalls, it helps to know which kind of slowdown it is.

Weight loss on semaglutide and tirzepatide levels off for nearly everyone, and a minority of people lose little from the start. This guide covers what the trials show, the factors researchers have looked at, and questions to take to your prescriber.

Reserve your spot Questions for your prescriber

A plateau is expected.
Little loss from the start is less common.

It helps to separate two things. A plateau after months of steady loss is expected, because weight loss on these drugs levels off within the first year or so. Non-response usually means little loss from the start, even after time at a maintenance dose.

  • How often people lose less than 5%

    In STEP 1, about 14% of participants without diabetes lost less than 5% of body weight on semaglutide 2.4 mg, and in SURMOUNT-1, 9–15% did on tirzepatide, depending on dose. In STEP 2, which enrolled people with type 2 diabetes, about 31% did on semaglutide 2.4 mg.123

  • When response is usually judged

    Prescribers typically judge weight response after about 12–16 weeks, or around 3 months at a maintenance dose, because the dose is raised slowly over the first months.

Factors researchers have looked at,
some better understood than others.

Several things can make weight loss on Ozempic, Wegovy, Mounjaro or Zepbound smaller than expected. The first few are well documented; the last two are early research.

  • Dose and time at dose

    These medicines are started at a low dose and raised over several months to limit nausea and other stomach side effects. Weight loss during the early, lower-dose months doesn’t show what the maintenance dose will do, which is one reason prescribers wait before judging response.

  • Type 2 diabetes

    People with type 2 diabetes lose less weight on average on the same drugs: about 10% versus 15% with semaglutide 2.4 mg in the STEP 2 and STEP 1 trials.12 Long-standing insulin resistance is thought to contribute, though the reasons aren’t fully understood, so the averages to compare against are lower.

  • Other medicines

    Some medicines work against weight loss. Corticosteroids such as prednisone raise blood sugar and promote weight gain, and some antipsychotics, beta-blockers and insulin secretagogues are associated with weight gain or a blunted metabolic response. That isn’t a reason to stop any of them; it is something to review with your prescriber.

  • Genetic variation

    Semaglutide and tirzepatide bind the GLP-1 receptor, which is encoded by a gene called GLP1R. Natural variations in this gene can change how the receptor binds the drug and signals. Studies have linked some variants to modestly different responses, but no genetic test can predict your response today.

  • The gut microbiome

    Early research suggests gut bacteria may influence appetite and metabolic signaling during GLP-1 therapy. Because injected semaglutide and tirzepatide are absorbed under the skin, any role would be in that signaling rather than in how the drug is absorbed. The evidence is still early.

Questions to take
to your prescriber.

Whether to change a dose, switch medication or try something else is a decision for you and your prescriber. These are questions people often raise.

  • Have I been at my maintenance dose long enough?

    Many people are still on a titration dose when they feel treatment has stalled. Your prescriber can tell you whether you have reached the dose they intend for you, how long they usually wait at it before judging response, and whether raising it is appropriate and safe for you.

  • Would a different medication make sense for me?

    GLP-1 medicines don’t all work the same way. Semaglutide (Ozempic, Wegovy) acts on the GLP-1 receptor, while tirzepatide (Mounjaro, Zepbound) acts on both the GLP-1 and GIP receptors. Your prescriber can weigh whether a switch makes sense for you, and how to map the dose and timing.

  • Could another medicine I take be part of it?

    Bring your full medication list. Corticosteroids, certain antipsychotics and other medicines can work against weight loss, and your prescriber can judge whether any of them matters in your case.

  • What about diet, activity and sleep?

    The prescribing information for these medicines describes them as an addition to a reduced-calorie diet and increased physical activity. Your prescriber or a dietitian can say what applies to you.

Weight is one measure.
Your inflammation system can move on its own.

In the SELECT trial, hs-CRP, a common blood marker of inflammation, fell by weeks 4 and 8, before major weight loss, and fell even in participants who did not lose weight.4

hs-CRP measures one protein. The Inflammation Compass reads which genes your immune cells are using, from the signals that start a response to the signals that end it, and reports six readings from 38 pathways, plus your immune cell mix. Your first sample starts your personal baseline. Across later samples, including before and after a dose change or a switch, it measures which parts of your inflammation system moved, by how much, and which stayed about the same.

See what the report includes

What it
can't tell you.

The Inflammation Compass shows what changed and by how much. It can’t show why, because many things move these readings, and it doesn’t show whether a medication is working, whether you are responding to it, or how much weight you will lose. It doesn’t diagnose, rule out or predict any disease.

What a change means is for you and your prescriber to weigh. Decisions about starting, adjusting, switching or stopping a medication stay with your prescriber.

Common questions about plateaus and non-response

  • How do I know if my GLP-1 isn’t working?

    Prescribers usually judge weight response after about 12–16 weeks, or around 3 months at a maintenance dose. They also look at appetite and at markers such as A1C, fasting glucose and lipids: fasting glucose moves within weeks, while A1C reflects the previous 2–3 months. Judging response is your prescriber’s call. The Inflammation Compass doesn’t show whether a medication is working; it measures which parts of your inflammation system moved across your samples.

  • What percentage of people don’t respond to Ozempic?

    In the STEP 1 trial, about 14% of participants without diabetes lost less than 5% of body weight on semaglutide 2.4 mg (Wegovy); in STEP 2, about 31% of participants with type 2 diabetes did.12 In the SURMOUNT-1 trial, 9–15% of participants without diabetes lost less than 5% on tirzepatide (Zepbound), depending on dose.3 So most participants lost at least 5%, and a minority didn’t, even at full doses in closely supervised trials.

  • Can I switch from Ozempic to Mounjaro if it’s not working?

    Switching between GLP-1–based medications is a common clinical option. Semaglutide (Ozempic, Wegovy) acts on the GLP-1 receptor alone, while tirzepatide (Mounjaro, Zepbound) acts on both the GLP-1 and GIP receptors. Whether to switch, and how to map the dose and timing, is your prescriber’s decision. If you give samples before and after a switch, the Inflammation Compass shows which of your readings moved between them.

  • What can the Inflammation Compass show during a weight plateau?

    It measures which parts of your inflammation system moved across your samples, and by how much. White blood cells carry little or no GLP-1 receptor, but GLP-1 therapy affects inflammation throughout the body: in the SELECT trial, hs-CRP fell before major weight loss and even in participants who did not lose weight.4 The Inflammation Compass reports six readings across Activation and Resolution, plus your immune cell mix, whether or not the scale is moving. It doesn’t show whether the medication is working, and decisions about dose or switching stay with your prescriber.

Read more

See which parts of your inflammation move across your samples.

Your first sample starts your personal baseline. Each later sample shows which of your six readings moved and by how much.

Reserve your spot What RNA adds
Sources and further reading

References

1. Wilding JPH, et al. (2021) — Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 384(11):989–1002. doi:10.1056/NEJMoa2032183. PMID 33567185.
2. Davies M, et al. (2021) — Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 397(10278):971–984. doi:10.1016/S0140-6736(21)00213-0. PMID 33667417.
3. Jastreboff AM, et al. (2022) — Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med. 387(3):205–216. doi:10.1056/NEJMoa2206038. PMID 35658024.
4. Plutzky J, et al. (2026) — Effect of semaglutide on the inflammatory biomarker high-sensitivity CRP in patients with established cardiovascular disease and overweight or obesity in SELECT: a prespecified secondary analysis. Circulation. 154(11):976–991. doi:10.1161/CIRCULATIONAHA.125.074482. PMID 42610271.