Semaglutide or Tirzepatide – which is more effective for weight loss?

How does semaglutide work?

Semaglutide is a GLP-1 receptor agonist that mimics the effect of the body's natural satiety hormone, glucagon-like peptide-1 (GLP-1). By activating these receptors, gastric emptying is delayed and satiety signals are amplified, which can contribute to reduced energy intake. GLP-1 is normally released from the small intestine in connection with food intake, and pharmacological administration provides a more long-lasting and stable satiety effect.

Semaglutide is the active substance in medications such as Wegovy, which is approved for weight treatment in cases of obesity and overweight with weight-related complications in adults, as well as Ozempic, which is indicated for the treatment of type 2 diabetes. In addition to its peripheral effects, semaglutide also influences central mechanisms in the brain, including areas linked to appetite regulation and reward, which can contribute to reduced cravings for energy-dense foods (reducing so-called "food noise").

This can make it easier to maintain the energy deficit required to lose weight without constantly having to struggle against intense hunger. Furthermore, semaglutide has a blood sugar-balancing effect by stimulating insulin secretion in a glucose-dependent manner and inhibiting glucagon release when blood sugar levels are elevated. This is of particular importance when treating individuals with type 2 diabetes.

Tirzepatide compared to semaglutide – different mechanisms of action

Tirzepatide is a so-called dual agonist that activates both GLP-1 and GIP receptors. Like semaglutide, it mimics GLP-1 and contributes to reduced appetite and delayed gastric emptying. Through simultaneous activation of the GIP receptor, a broader metabolic impact can be achieved.

This active substance is found in the medication Mounjaro, which is approved for both weight control in obesity and for the treatment of type 2 diabetes in adults, as a supplement to diet and exercise.

What is the difference between tirzepatide and semaglutide as GLP-1-based medications?

The main biological difference is that semaglutide selectively activates the GLP-1 receptor, while tirzepatide is a dual agonist that activates both GLP-1 and GIP receptors.

Both medications are typically administered once weekly via subcutaneous injection – an injection into the subcutaneous fat, usually in the abdomen or thigh – using a pre-filled injection pen.

Semaglutide is also available in oral form (Rybelsus) for daily administration. This may be an alternative for patients who prefer to avoid injections, although the indication is primarily approved for the treatment of type 2 diabetes.

Which treatment provides the greatest weight loss in people living with obesity?

Clinical studies in individuals with obesity without type 2 diabetes show that tirzepatide, on average, provides a slightly greater weight loss than semaglutide. In treatment with semaglutide 2.4 mg, an average weight reduction of approximately 15 percent was achieved after 68 weeks of treatment. For tirzepatide, studies have shown a greater average weight loss, around 20 percent after 72 weeks at doses of 10 mg and 15 mg.

In a direct comparative "head-to-head" study (SURMOUNT-5), participants treated with tirzepatide achieved a greater average weight loss than those who received semaglutide.

However, it is important to emphasise that these results refer to averages at a group level. Both treatments provide clinically significant weight loss. The individual effect varies and is influenced by factors such as treatment adherence, tolerability, and the extent to which lifestyle measures are integrated into the treatment.

Side effects – do they differ?

The side effect profile for semaglutide and tirzepatide is largely similar and is dominated by gastrointestinal symptoms such as nausea, diarrhoea, and constipation, especially at the start of treatment. These side effects are mainly related to the medications' effects on gastric emptying and central mechanisms for appetite regulation.

The discomfort is often most pronounced during the first weeks of treatment or in connection with dose escalation. Gradual dose increase is therefore used to improve tolerability.

To reduce the risk of gastrointestinal issues, it can be beneficial to adjust meal size and meal patterns. Dose adjustment should be individualised and based on efficacy and tolerability.

Rare but serious side effects, such as acute pancreatitis, have been reported in patients treated with both medications. If pancreatitis is suspected, treatment should be discontinued and the patient medically assessed.

What should one think when choosing?

The choice of medication should always be based on an individual medical assessment, taking into account the patient's medical history, treatment goals, and circumstances. Some patients achieve good results and tolerate semaglutide well, while others may benefit more from tirzepatide depending on treatment response and needs.

Before a doctor's visit, it may be valuable to reflect on the following:

• What are my goals for the treatment, for example, regarding weight loss and health?
• Which administration form do I prefer (subcutaneous injection or oral treatment)?
• Which previous illnesses and current medications are relevant to take into account?

The treatment should be followed up regularly and adjusted based on efficacy, tolerability, and individual needs. In many cases, a multidisciplinary approach, including medical treatment combined with lifestyle support, can contribute to a more sustainable treatment result.

Frequently Asked Questions (FAQ) about Semaglutide vs Tirzepatide

Is tirzepatide more effective than semaglutide?

Direct clinical studies have shown that tirzepatide (Mounjaro) on average provides a slightly greater weight loss than semaglutide (Wegovy).

How much weight can you lose?

In treatment with semaglutide (Wegovy), an average weight reduction of approximately 15 percent is achieved after just over a year of treatment. For tirzepatide (Mounjaro), studies have shown an average weight loss of up to approximately 20 percent.

However, results vary between individuals and are highly dependent on treatment adherence and the extent to which lifestyle measures are integrated into the treatment.

Can you switch from semaglutide to tirzepatide?

Yes, it is possible to switch treatment, for example, in the case of insufficient efficacy or bothersome side effects. Such a switch should always take place in consultation with a treating doctor who can ensure a suitable transition and correct dose escalation of the new medication.

Which treatment is best for me?

The choice of treatment is based on an individual medical assessment, where factors such as BMI, potential comorbidities (e.g., hypertension or pre-diabetes), and the patient's preferences are considered. The treating doctor determines which therapy is most appropriate based on these conditions.

Sources

The New England Journal of Medicine (NEJM). Once-Weekly Semaglutide in Adults with Overweight or Obesity
https://www.nejm.org/doi/full/10.1056/NEJMoa2032183

The New England Journal of Medicine (NEJM). Tirzepatide as Compared with Semaglutide for the Treatment of Obesity
https://www.nejm.org/doi/full/10.1056/NEJMoa2416394

The New England Journal of Medicine (NEJM). Tirzepatide Once Weekly for the Treatment of Obesity
https://www.nejm.org/doi/full/10.1056/NEJMoa2206038

European Medicines Agency (EMA). Wegovy
https://www.ema.europa.eu/en/medicines/human/EPAR/wegovy

European Medicines Agency (EMA). Mounjaro
https://www.ema.europa.eu/en/medicines/human/EPAR/mounjaro