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Steroids & Peptides Comparison

Semaglutide vs Tirzepatide: What the Numbers Actually Say

Posted on by GH Canada

Semaglutide is the active ingredient in both Ozempic and Wegovy. On the other hand, Tirzepatide is the active ingredient in Mounjaro and Zepbound. Both are once-a-week injections, both are really good at curbing appetite, and both have more published human studies to their credit compared to any other drug available in the market for weight loss. The million-dollar question we keep getting is which one to test, so here’s the answer.

How they work

Semaglutide is an agonist of the GLP-1 receptor. GLP-1 is a gut hormone released by your body after meals. The effects of GLP-1 include slower stomach emptying, suppression of appetite at the brain level, and enhancement of your glucose metabolism. Therefore, semaglutide is a long-acting form of this messenger, that is why you can get away with only one injection for a whole week.
Tirzepatide is similar to Semaglutide in its effects, but in addition, it activates the GIP receptor. GIP is another incretin hormone playing an important role in metabolism. There is no consensus yet about the reason for the increased efficacy of this two-pronged approach, but the results of experiments show that stimulating both receptors leads to greater weight loss than stimulating only GLP-1.

The head-to-head numbers

In fact, for years these two drugs could only be compared in separate trials. However, since 2025 there is a direct head-to-head comparison between them; there is nothing more to argue about.

TrialCompoundDurationAverage weight loss
STEP 1Semaglutide 2.4mg weekly68 weeksabout 15%
SURMOUNT-1Tirzepatide 15mg weekly72 weeksabout 21%
SURMOUNT-5 (head to head)Tirzepatide vs semaglutide72 weeksabout 20% vs about 14%
SURMOUNT-5 is the study that proves it. Same study, same circumstances, same maximum tolerable dosage of both drugs: tirzepatide showed a lead of almost 6%. On a 100-kilogram patient, this translates to a difference between 14 kilograms of weight loss and 20 kilograms.
However, this does not make semaglutide ineffective. Weight loss up to 15% of body mass has never been achieved with any drug prior to their discovery, and many patients have everything they need with just semaglutide. It is just the more effective of the two.

Side effects are nearly identical

And in fact both drugs have the exact same warning list, due to the mechanism of GLP-1 action – nausea, constipation or diarrhea, and rare cases of vomiting, usually in the first few weeks after dose escalation. It resolves itself after some time for most people, and that’s why both of them have a very careful dose escalation process.
The serious warnings are common for both as well – the thyroid tumor potential found in rodents (thus patients with history of medullary thyroid cancer or its family history cannot use any GLP-1 analogs) and rare pancreatitis and gallbladder issues. There isn’t a single significant difference between drugs in this regard.
Two practical tips that both of them require. Have smaller meals than you think you need, especially in the beginning, since the food stays in your stomach significantly longer. Drink more water than usual, as in almost all of those “bad first week” cases the dehydration was a key factor.

Dosing schedules compared

Both are injected under the skin once a week, any time of day, with or without food. The published titration schedules look like this:

SemaglutideTirzepatide
Starting dose0.25mg weekly2.5mg weekly
Step-ups0.5 → 1 → 1.7 → 2.4mg, one step every 4 weeks5 → 7.5 → 10 → 12.5 → 15mg, one step every 4 weeks
Full dose2.4mg weekly15mg weekly
Half-lifeabout a weekabout 5 days

Do not read the milligram numbers across the columns; they are different molecules and the doses are not comparable. What matters is that both ramp up over several months, and skipping the ramp is the most reliable way to have a miserable time on either one.

If you train, read this part

This is skipped by the clinic blog posts, but it’s crucial to our audience because the quick weight loss caused by both of these medications loses lean mass along with body fat. Sub-studies of the body composition in the GLP-1 class have shown that a substantial portion of the weight loss may be made up of lean mass if something isn’t done about it.
The solution to this problem is simple. Make sure to keep your protein intake high despite lack of appetite, which is the true challenge with these two drugs, and continue exercising during the cut. Those who exercise while under the influence of a GLP-1 drug retain their muscle far better than those who simply stop eating.

What they cost in Canada

With either medication available via a pharmacy on a prescription, without insurance, and for a few hundred dollars per month, the branded tirzepatide is generally more expensive than the semaglutide. The availability of coverage varies between provinces and plans, while most plans that do have coverage only provide it for the diabetes medications.
We carry both drugs in research vial form, priced in Canadian Dollars:
  • Semaglutide GH — $70 per vial. The budget way into the GLP-1 class.
  • TRZ GLP2 (tirzepatide) — from $126 for the 5mg vial, with 20mg and 30mg options for US delivery. The 30mg is currently 20% off at $400 for US orders.

The vials originate from within Canada and come in discreet packing. This list indicates precisely the contents of the vial as well as delivery methods because higher dosages of tirzepatide are for US only.

So which one should you pick?

Choose tirzepatide if your main priority is the maximum weight loss and you are looking for the most efficacious compound by the numbers. This drug came out ahead in the direct comparison, and it is the one which currently defines the term “most powerful” for most people.
Choose semaglutide if the aim is the longest history of testing, the lowest price of access, or the softer start with the GLP-1 drugs before considering going further. Fifteen percent average weight loss is also an outstanding figure, and this compound boasts the greatest number of years of practical experience.
However, it should be remembered that this category of drugs helps with weight loss only while it is taken. Appetite returns once the treatment is stopped, and post-treatment observation studies demonstrate the return of the majority of weight gained during the experiment in just one year in case of no strategy for nutrition and exercises developed. The drug is the means which allows making a habit change possible.

Can you switch from one to the other?

Yes, and it is common, usually from semaglutide to tirzepatide when weight loss stalls. There is no published washout protocol; the sensible approach is to finish one, start the other at a low-to-mid dose rather than jumping straight to the top, and let the same ramp-up logic apply. Going the other direction, tirzepatide to semaglutide, mostly happens for cost or availability reasons.

What about retatrutide?

Retatrutide is the next one down the pipeline: it adds a third receptor (glucagon) on top of GLP-1 and GIP. Phase 2 results showed around 24% average weight loss at 48 weeks, which beats anything above, but phase 3 is still running and there is far less safety data. We stock retatrutide 10mg for the people who follow the research closely. For everyone else, semaglutide and tirzepatide are the two with the full evidence base today.

Quick answers

Is tirzepatide stronger than semaglutide?
Yes. In the SURMOUNT-5 head-to-head trial, tirzepatide averaged about 20% weight loss versus about 14% for semaglutide over 72 weeks at maximum tolerated doses.

Are the side effects worse on tirzepatide?
Not meaningfully. Both cause the same GI side effects during dose increases, and discontinuation rates in the head-to-head were similar.

How fast do they work?
Appetite suppression starts within the first week or two on either drug. Meaningful weight change shows up over months, not weeks, partly because both spend the first two to three months at low ramp-up doses.

Do you regain the weight after stopping?
Most people regain most of it within a year if nothing else changes. That is true for both drugs. Food habits and training are what make the result stick.

Sources

  1. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 2021 (STEP 1). https://doi.org/10.1056/NEJMoa2032183
  2. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine, 2022 (SURMOUNT-1). https://doi.org/10.1056/NEJMoa2206038
  3. Aronne LJ, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. New England Journal of Medicine, 2025 (SURMOUNT-5, the head-to-head trial). https://doi.org/10.1056/NEJMoa2416394
  4. Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes, Obesity and Metabolism, 2022. https://doi.org/10.1111/dom.14725
  5. Aronne LJ, et al. Continued Treatment with Tirzepatide for Maintenance of Weight Reduction. JAMA, 2024 (SURMOUNT-4). https://doi.org/10.1001/jama.2023.24945
  6. Prado CM, et al. Muscle matters: the effects of medically induced weight loss on skeletal muscle. The Lancet Diabetes & Endocrinology, 2024. https://doi.org/10.1016/S2213-8587(24)00272-9
  7. Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity. New England Journal of Medicine, 2023 (phase 2). https://doi.org/10.1056/NEJMoa2301972
  8. Wegovy (semaglutide) and Mounjaro (tirzepatide) product monographs, Novo Nordisk / Eli Lilly — titration schedules, contraindications and safety warnings.
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With over a decade of experience in the world of anabolic steroids and performance enhancement, our GH Canada expert is a trusted authority in the industry. Passionate about fitness, bodybuilding, and sports nutrition, he has dedicated his career to educating others on the safe and effective use of anabolic steroids.

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