Why Am I Not Losing Weight on Semaglutide or Tirzepatide? A Doctor Explains the 7 Most Common Reasons
- Joshua Silva, MD
- 21 hours ago
- 7 min read
Medically authored by Joshua Silva, MD | Evidence-Based Weight Loss at Potere Health MD
Quick Answer
Most people who aren’t losing weight on GLP-1 medications like semaglutide (Wegovy®) or tirzepatide (Zepbound®) are not resistant to the medication.
The most common reasons are being on a dose that is not yet therapeutic, consuming more calories than expected, inconsistent dosing, normal weight-loss plateaus, or medical or medication-related factors that affect weight regulation.
True pharmacologic non-response exists, but it should only be considered after adequate time at a therapeutic dose and a clinical review.
How Much Weight Should You Lose on Semaglutide or Tirzepatide?
These medications produce large average weight loss, but individual response varies.
Semaglutide (Wegovy®)
In the STEP-1 trial, adults with obesity or overweight treated with semaglutide 2.4 mg lost about 14.9% of body weight at 68 weeks, compared with 2.4% with placebo, and approximately 86% achieved at least 5% weight loss.
Tirzepatide (Zepbound®)
In the SURMOUNT-1 trial at 72 weeks:
5 mg → ~15% average weight loss
10 mg → ~19.5%
15 mg → ~20.9%
Placebo lost ~3%.
Key point:
In both trials, weight loss accrued over many months, and participants were titrated gradually to their maintenance dose. Early weeks of treatment are primarily for dose escalation and tolerability, so slower loss early in therapy is expected.
Why Semaglutide or Tirzepatide May Not Be Working Yet
1) Am I on a high enough dose of semaglutide or tirzepatide yet?
Often, no—especially in the first months.
Wegovy® is titrated to a recommended maintenance dose of 2.4 mg weekly (or 1.7 mg if 2.4 mg is not tolerated).
Zepbound® starts at 2.5 mg weekly for 4 weeks, which is an initiation dose, not a maintenance dose, and can be increased in 2.5 mg steps after at least 4 weeks at each dose.
Bottom line:
If you are still on starter or early titration doses, slower or minimal weight loss does not mean the medication has failed.
What to do:
If you are tolerating your current dose but not losing weight, ask your clinician whether it is appropriate to increase to the next scheduled dose.
2) Could I still be eating too many calories on semaglutide or tirzepatide?
Yes. GLP-1/GIP medications reduce appetite and cravings, but fat loss still requires a sustained energy deficit. Large clinical trials show strong average weight loss, but individual results vary.
In clinical practice, common sources of unintended calories include:
Liquid calories (sweetened drinks, alcohol, coffee beverages)
Frequent snacking or grazing
Calorie-dense foods eaten in small volumes (oils, nuts, cheese, fried foods, processed or pre-packaged snacks)
Bottom line:
Lower appetite does not always guarantee lower calorie intake.
What to do:
Track your food and beverages for 3–7 days, focusing especially on liquid calories, snacking, and high-fat foods, and review the pattern with your clinician or nutrition team to identify hidden sources of excess calories.
3) Can eating too little slow weight loss on GLP-1 medications?
It can contribute to a stall indirectly.
Weight-loss physiology literature describes adaptive thermogenesis, where energy expenditure decreases more than expected during sustained calorie restriction and weight loss. This can make further loss harder and can reduce adherence in some patients.
Bottom line:
Very aggressive restriction is not always necessary and may be difficult to sustain.
What to do:
If you feel exhausted, lightheaded, or overly restricted, talk with your clinician about increasing protein and overall intake slightly to make your weigh loss plan more sustainable.
4) Does not eating enough protein affect semaglutide or tirzepatide results?
Yes — but not because protein itself causes fat loss.
Studies of semaglutide and tirzepatide show that people lose both fat and muscle. Preserving muscle matters because muscle burns more calories at rest and helps prevent metabolic slowdown as weight falls.
Protein also helps in two practical ways:
It increases satiety, so you feel full longer
It slows digestion, which helps you stay satisfied and may lead to eating fewer calories over time
Together, this supports more sustainable fat loss while helping protect metabolism.
Bottom line:
Protein and strength training support lean-mass preservation, which is important for long-term metabolic health.
What to do:
Ask your clinician for a personalized protein target — often starting with about 25–30 grams per meal — and whether adding resistance training is appropriate to help preserve lean mass during weight loss.
Can missed or late injections make semaglutide or tirzepatide less effective?
Yes — especially if doses are missed repeatedly or taken every other week.
These medications work best when drug levels stay steady. Skipping doses or spacing injections too far apart lets levels drop, which can allow hunger and calorie intake to return.
Some patients are told to inject every other week to reduce side effects, but this causes fluctuating drug levels and is not how these medications were studied or approved.
Bottom line:
Inconsistent dosing can reduce the appetite control these medications provide.
What to do:
Take your injection weekly as prescribed. If side effects are an issue, talk with your clinician about adjusting the dose instead of spacing injections out.
6) Is a weight-loss plateau normal on semaglutide or tirzepatide?
Yes.
As body weight decreases, the body requires fewer calories, and the metabolic rate adjusts downward. Over time, the body reaches a new energy balance where calorie intake and calorie use come back into equilibrium, even on a lower-calorie diet. This is a normal physiologic response and is why plateaus occur during long-term weight loss.
Bottom line:
A plateau does not mean the medication has stopped working — it usually means the plan or dose needs reassessment.
What to do:
If your weight has plateaued for several weeks, review your calorie intake, activity level, and medication dose with your clinician to determine whether reducing calories, increasing physical activity, or adjusting the dose is appropriate.
7) Can medical conditions or medications interfere with GLP-1 weight loss?
Yes.
Clinical obesity guidelines recommend evaluating secondary contributors when weight loss is less than expected, including:
Weight-promoting medications (e.g., some antidepressants, antipsychotics, steroids, insulin, sulfonylureas)
Endocrine conditions such as hypothyroidism (when clinically suspected)
Insulin resistance, PCOS
Sleep disorders such as sleep apnea
Bottom line:
Medical and medication factors can blunt even effective therapies.
What to do:
Ask your clinician to review your medications and screen for conditions such as hypothyroidism, sleep apnea, or insulin resistance if weight loss is less than expected.
Do Some People Not Respond to Semaglutide or Tirzepatide?
Yes—but far fewer than many people think.
In obesity pharmacotherapy, a patient is generally considered a true non-responder if they fail to lose at least 5% of baseline body weight after about 12 weeks at a therapeutic dose—not simply 12 weeks after starting.
This distinction matters because both semaglutide and tirzepatide require gradual dose escalation, and many patients spend their early months on sub-therapeutic doses.
In large clinical trials, most patients achieved meaningful weight loss. About 86% of people taking semaglutide (Wegovy®) and 85–91% of those taking tirzepatide (Zepbound®) reached at least 5% weight loss, meaning only about 9–15% met criteria for non-response.
Importantly, post-hoc analyses of tirzepatide trials show that many patients who did not meet early response benchmarks were actually slow responders — and nearly 90% of these late responders still reached ≥5% weight loss by 72 weeks. In other words, slow response is not the same as drug failure.
Before labeling someone a non-responder, clinicians should confirm:
Adequate time at a therapeutic dose
Consistent adherence
That dietary, medication, and medical barriers have been addressed
Bottom line:
Most people who believe the medication “isn’t working” are actually early in treatment, under-dosed, or facing correctable barriers.
What to do:
If weight loss is less than expected, first confirm that you’ve had enough time at a therapeutic dose with consistent weekly injections.
If you still do not reach meaningful weight loss after adequate dosing and time, talk with your clinician about whether switching to a different GLP-1 or GLP-1/GIP medication may be appropriate.
When Should You Call Your Clinician?
Contact your clinician if you have:
Persistent vomiting or diarrhea
Signs of dehydration
Severe abdominal pain
Inability to tolerate dose escalation
Bottom Line
If semaglutide or tirzepatide isn’t producing weight loss yet, the problem is usually not the medication itself—it is most often dose, time, consistency, intake, or normal physiology.
With proper dosing, monitoring, and support, most patients can achieve clinically meaningful weight loss.
Disclaimer
This article is for educational purposes only and is not a substitute for medical advice.
About the Author
Dr. Joshua Silva, MD, is a licensed physician and Medical Director of Potere Health MD. He earned his medical degree from the University of Hawaiʻi John A. Burns School of Medicine and completed residency training in Occupational and Environmental Medicine at the University of Utah, where he also earned a master’s degree in Occupational Health. He later completed a Master of Business Administration with an emphasis in health care administration at Ohio University.
Dr. Silva specializes in evidence-based weight management, including GLP-1 and GIP therapies such as semaglutide and tirzepatide. He provides in-person and virtual care for patients in Salt Lake City, St. George, and Cedar City, Utah.
Sources
Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP-1). N Engl J Med.2021;384(11):989-1002. Published clinical trial demonstrating ~14.9% mean weight loss and ~86% ≥5% weight loss at 68 weeks with semaglutide 2.4 mg vs placebo. NEJM. doi:10.1056/NEJMoa2032183. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med.2022;387(3):205-216. Pivotal 72-week trial showing substantial mean weight loss (5 mg ~15%, 10 mg ~19.5%, 15 mg ~20.9%) and high rates of clinically meaningful loss. Available at: https://pubmed.ncbi.nlm.nih.gov/35658024/
U.S. Food and Drug Administration. ZEPBOUND® (tirzepatide) Injection US Prescribing Information. FDA. 2025. Details recommended initial dose, escalation schedule, and maintenance dosing for Zepbound. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/217806Orig1s020lbl.pdf
Singh A, et al. Tirzepatide: Predictors of Responders vs. Non-Responders. Clin Diabetol. 2025;43(2):231-240. Observational and post-hoc data indicating variability in weight responses and non-responder proportions in tirzepatide and semaglutide trials. Available at: https://journals.viamedica.pl/clinical_diabetology/article/download/106515/83444
Ard J, et al. Weight Reduction over Time in Tirzepatide-Treated Adults with Obesity (SURMOUNT-1 Post-Hoc Analysis). PMC. 2025;278 slow responders analysis showing ~89.4%–96.3% achieving ≥5% weight loss across doses and ~90% of late responders reaching ≥5% by week 72. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC12326891/
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