Medical weight loss

What these medicines are

The current generation are GLP-1 receptor agonists — semaglutide and liraglutide — and the dual GIP/GLP-1 agonist tirzepatide. They imitate gut hormones released after eating. They slow stomach emptying, increase how full you feel, and reduce the constant background pull towards food that most people carrying excess weight will recognise immediately.

That last effect is the one patients describe as the difference. The medicine does not remove the need to eat well; it makes eating well possible, by quietening the signal that made it feel like a fight.

How much weight, honestly

In the STEP 1 trial, adults with obesity and without diabetes taking semaglutide 2.4 mg weekly for 68 weeks lost an average of 14.9% of body weight, against 2.4% on placebo. Half of them lost 15% or more.

In SURMOUNT-1, tirzepatide over 72 weeks produced an average loss of 15.0% at 5 mg, 19.5% at 10 mg and 20.9% at 15 mg, against 3.1% on placebo.

Two things to hold alongside those numbers. Both trials paired the drug with structured lifestyle support, which is part of the result and not a footnote. And people with type 2 diabetes consistently lose somewhat less on the same doses than people without it.

Older options remain reasonable where cost or supply is the constraint. Liraglutide 3.0 mg is a daily injection with a smaller effect. Orlistat is oral, works by blocking fat absorption, has a modest effect and unpleasant consequences if you eat fat while taking it.

Side effects and who should not take them

Nausea, vomiting, constipation, diarrhoea and reflux are common, worst during dose escalation, and are the reason the dose is stepped up slowly over months rather than started at target. Most settle. Some people cannot tolerate them at all.

Less common but important: gallstones, which become more likely with any rapid weight loss; pancreatitis, which is rare; and dehydration from persistent vomiting, which matters a great deal if you are also on an SGLT2 inhibitor or a diuretic.

These medicines should not be used in pregnancy or while trying to conceive, and should be stopped well in advance. The class is not given to anyone with a personal or family history of medullary thyroid carcinoma or MEN2 syndrome. If you have gastroparesis, or a history of pancreatitis, they need careful thought.

Muscle loss is a genuine concern at these rates of weight loss. Protein intake and resistance exercise are not optional extras alongside these drugs; they are part of the prescription.

What happens when you stop

Weight returns. In trials where the medicine was withdrawn, most of what was lost came back over the following year, and the improvements in blood pressure and glucose went with it. This is the single most important thing to understand before starting.

It is not an argument against the medicines. It is an argument against thinking of them as a course of treatment with an end date. Obesity behaves like hypertension: treatment works while it is being taken. If cost means you can only sustain a year of it, we should plan that year — and the transition out of it — deliberately, rather than discovering the problem when the last pen runs out.

Who this is reasonable for

Broadly: a BMI at or above 27.5 with a weight-related condition such as type 2 diabetes, prediabetes, fatty liver, sleep apnoea, hypertension or PCOS, or a BMI at or above 32.5 on its own, using the Asian thresholds. Alongside, not instead of, a diet and activity plan.

It is not reasonable as a way to lose five kilograms before a wedding, and it is not reasonable without follow-up. What we do here is assess whether you are a candidate, start and escalate the dose with review at each step, watch for the side effects that matter, and adjust your other medicines as your weight and glucose change — because they will.

Sources

Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021;384:989–1002. Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022;387:205–216.