Obesity medicines: what to know about semaglutide and tirzepatide

Semaglutide and tirzepatide have opened a new era in obesity treatment. They work, but they are not simply “weight-loss jabs”: they need the right indication, follow-up and a plan to preserve muscle.

Key points

In the main trials, average weight loss was around 15% with semaglutide and up to 20% with tirzepatide.
Semaglutide reduced cardiovascular events in people with cardiovascular disease and overweight or obesity.
The most common side effects are digestive and usually improve with gradual dose increases.

Obesity is a chronic disease

Body weight is regulated by hormonal signals between the gut, fat tissue and the brain. That is why, for many people, diet and exercise, while essential, are not enough on their own: the body “defends” lost weight by increasing hunger and reducing energy expenditure.

How they work

Semaglutide mimics the gut hormone GLP-1; tirzepatide acts on both GIP and GLP-1 receptors. Both increase fullness, reduce appetite and slow stomach emptying. They are given as a weekly injection.

What the trials show

STEP 1: semaglutide 2.4 mg achieved an average loss of about 15% of body weight at 68 weeks, versus about 2% with placebo.
SURMOUNT-1: with tirzepatide, average loss ranged from 15% to 21% depending on the dose at 72 weeks.
SELECT: in people with established cardiovascular disease and overweight or obesity without diabetes, semaglutide reduced major cardiovascular events by 20%.

What to watch for

Digestive effects: nausea, diarrhoea, constipation or vomiting, mainly at the start. Increasing the dose gradually minimises them.
Muscle mass: part of the weight lost is muscle. Adequate protein and strength training are part of the treatment.
Contraindications: personal or family history of medullary thyroid carcinoma or MEN 2, pregnancy and breastfeeding, among others.
Stopping treatment: weight regain is common, so plan from the start how results will be maintained.

When to seek advice

These medicines are generally indicated with a body mass index of 30 or more, or 27 or more with related conditions such as hypertension, prediabetes or sleep apnoea. They require a prescription and medical follow-up: do not use them unsupervised.

References

Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002.
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216.
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232.

This article is for information only and does not replace medical advice. If you have questions about your case, talk to your doctor.