The New Weight Loss Medicines: What They Do, What They Cost You
For the first time, there are medicines that produce weight loss approaching what surgery achieves. That is genuinely significant, and it has also produced a wave of marketing that leaves out most of the important detail.
How they work
These drugs mimic gut hormones released after eating.
GLP-1 receptor agonists such as semaglutide and liraglutide slow stomach emptying, act on appetite centres in the brain to increase satiety and reduce food-seeking thoughts, and improve insulin secretion in response to glucose.
Dual GIP and GLP-1 agonists such as tirzepatide act on a second gut hormone receptor as well, and in trials have produced larger average weight loss.
The subjective experience most people describe is a marked reduction in appetite and in the constant background preoccupation with food, often called food noise.
How much weight
In trials, average weight loss over roughly a year to 18 months has been in the region of 15 per cent of body weight with semaglutide at the obesity dose, and higher with tirzepatide, with considerable variation between individuals.
For comparison, lifestyle intervention alone typically produces 3 to 5 per cent sustained, and bariatric surgery 25 to 30 per cent.
Who they are for
- BMI of 30 or above
- BMI of 27 or above with a weight-related condition such as type 2 diabetes, hypertension, sleep apnoea, fatty liver or dyslipidaemia
- Lower BMI thresholds apply for people of South Asian and some other ancestries, because metabolic risk occurs at lower BMI
They are not intended for cosmetic weight loss in people at a healthy weight.
Side effects
Very common, and usually dose-related:
- Nausea, often worst after each dose increase and improving over weeks
- Vomiting
- Constipation or diarrhoea
- Reflux
- Burping, abdominal discomfort
- Fatigue and headache early on
Most of this is managed by escalating the dose slowly, eating smaller portions, stopping at the first sign of fullness, avoiding fatty and very large meals, and maintaining fluid and fibre.
Less common but important:
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- Pancreatitis. Severe persistent abdominal pain radiating to the back, with vomiting, requires stopping the drug and urgent assessment
- Gallstones. Rapid weight loss raises gallstone risk
- Dehydration and kidney injury, usually secondary to prolonged vomiting
- Gastroparesis, significantly delayed stomach emptying, which can persist
- Hypoglycaemia when combined with insulin or sulfonylureas, which usually need dose reduction
- Diabetic retinopathy can worsen with very rapid glucose improvement
- Anaesthesia risk from retained stomach contents, which is why these drugs are usually paused before planned surgery or endoscopy
Contraindicated in personal or family history of medullary thyroid carcinoma or MEN2 syndrome, and not used in pregnancy.
The muscle loss problem
This is the part most often left out.
A substantial share of weight lost on these drugs is lean mass, with estimates in trials commonly in the range of a quarter to 40 per cent of total weight lost. That proportion is broadly similar to other forms of rapid weight loss, but the absolute amount is larger because the weight loss is larger.
Losing muscle matters. It reduces resting metabolic rate, making regain easier; it reduces strength and function, which is particularly consequential in older adults; and it worsens long-term metabolic health.
The mitigation is not optional:
- Resistance training two to three times a week. The single most important countermeasure
- Adequate protein, typically 1.2 to 1.6 g/kg, which is harder than it sounds when appetite is suppressed. Protein should be prioritised at every meal, before other foods
- Adequate overall nutrition. Eating very little of a poor-quality diet produces deficiencies
- Monitoring body composition rather than only the scale, where available
What happens when you stop
Trials that withdrew the drug found that most of the lost weight returned over the following year, and that the metabolic improvements largely reversed with it.
This is not a failure of willpower. Obesity behaves as a chronic relapsing condition, and these drugs treat it while they are being taken, in the same way that antihypertensives lower blood pressure while being taken. The implication is that for most people this is long-term treatment, not a course.
That has consequences worth thinking about in advance: ongoing cost, long-term safety data that is still accumulating, and supply availability.
Compounded and online versions
Compounded semaglutide and products sold through unregulated online channels have been associated with dosing errors, incorrect salt forms of the active ingredient, and contamination. Several regulators have issued warnings. The price difference is real; so is the risk.
What has not changed
The medicines reduce appetite. They do not make food choices, build muscle, or teach eating patterns that survive stopping.
The people who do best combine the drug with resistance training, a protein-adequate diet, enough fibre to manage constipation, sleep, and ideally structured behavioural support.
The short version
These drugs work, and they work while you take them. The two things most likely to be missed are muscle loss, which needs resistance training and deliberate protein intake from the first week, and the fact that stopping usually means regaining. Decide in advance whether you are starting a long-term treatment, because that is what the evidence says this is.