Losing weight with Mounjaro: what tirzepatide does and which values shift

Losing weight with Mounjaro works through two gut hormones at once, GLP-1 and GIP. In the SURMOUNT-1 trial, participants on the highest dose lost an average of 20.9% of their body weight over 72 weeks (Jastreboff et al., 2022).

That is the highest figure any weight loss injection has produced in a large trial so far.

Here is what strikes me about it. The harder a drug works, the less often anything gets measured. Nearly every Dutch page about Mounjaro is about where you can obtain it.

Below is what tirzepatide does, and which values can move over the same period.

How much weight came off in the trials?

In SURMOUNT-1 participants received tirzepatide at three doses or a placebo for 72 weeks. Average weight loss rose with the dose. At 15 mg roughly 57% of participants lost more than a fifth of their body weight. These are group averages and say nothing about an individual result.

In the SURPASS-2 trial tirzepatide was compared head to head with semaglutide 1 mg in people with type 2 diabetes. Tirzepatide produced a larger reduction in both HbA1c and weight (Frias et al., 2021).

What does tirzepatide do differently from a plain GLP-1 drug?

Semaglutide works on one route: GLP-1. Tirzepatide works on GLP-1 and on GIP, a second hormone from your duodenum. GIP plays a part in insulin and in how your body stores fat. The thinking behind the combination is that two routes together reach further than one.

In practice people notice little difference in how it feels. Hunger falls away, just as with a GLP-1 drug.

The difference sits in the size of the drop, and therefore in what moves with it. More weight loss means more change in your fat mass, your muscle mass and your stores.

Which blood values shift on Mounjaro?

Three groups. The effect group shows whether your sugar handling responds: HbA1c, fasting glucose, fasting insulin and triglycerides. The safety group covers your pancreas, gallbladder and liver: lipase, amylase, ALT and gamma-GT. The third group covers what you still take in: ferritin, vitamin B12 and vitamin D.

Triglycerides often respond faster than LDL cholesterol. That surprises people, because most of the attention in the consulting room goes to LDL.

The safety group is not there because something is going wrong. It is there in case something stands out. A meta-analysis of 76 trials found an increased risk of gallbladder and biliary disease with GLP-1 drugs, particularly at higher doses and when used for weight loss (He et al., 2022).

The Dutch Voedingscentrum points out that weight loss goes together with loss of muscle mass and that adequate protein plays a role, citing 1.0 to 1.2 grams per kilogram of body weight for healthy older adults.

What relates to a dose increase?

Mounjaro is stepped up gradually, from 2.5 mg to higher doses. Many users notice gastrointestinal complaints returning in the days after each step. That pattern is well known and usually temporary. What is new at a higher dose is that your weight typically starts falling faster.

Falling faster means your intake drops further. Your vitamin stores follow that with a delay.

Say you ate well on 2.5 mg and have barely any appetite on 10 mg. Your ferritin from four months ago then says little about today.

The Dutch Farmacotherapeutisch Kompas describes the registered indication and the known side effects of tirzepatide. Severe abdominal pain radiating to your back belongs with a doctor the same day, not with a blood test.

What happens if you stop?

With semaglutide this has been studied most clearly. In the STEP 4 trial, people who continued lost a further 7.9% of their weight, while the group switched to placebo gained 6.9% over the same period (Rubino et al., 2021). For tirzepatide the picture points the same way.

The drug keeps your appetite low for as long as you use it. Stop, and hunger returns.

That makes the moment of stopping worth recording. Your HbA1c and your weight start moving again, and without a measurement you only learn how far things went once it has already happened.

What I see people do most often is measure at the start and then never again. I think tapering off is where a measurement earns its keep, because that is when something changes again.

Our GLP-1 extended panel is built around that wider picture, assessed by a BIG-registered doctor. If you want to see the difference from semaglutide, read Ozempic or Mounjaro. If you are curious about the pace, see how fast Mounjaro works, and for the complaints see Ozempic side effects.

If you are thinking about tapering off soon, record your values before the last injection.

References

• Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022. PMID 35658024
• Frias JP et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021. PMID 34170647
• Rubino D et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance (STEP 4). JAMA. 2021. PMID 33755728
• He L et al. Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases. JAMA Intern Med. 2022. PMID 35344001
• Farmacotherapeutisch Kompas, monograph for tirzepatide.
• Voedingscentrum, factsheet on older adults and nutrition (protein requirement).

Every blood test result includes a professional assessment from a BIG-registered doctor. For treatment decisions, discuss your results with your GP.