How GLP-1 weight-loss medicines work, and what the trials show
They work because they turn up a hormone signal your gut, pancreas and brain already use to negotiate about food, not because you finally found willpower. Here's the mechanism in plain terms, what the published trials found, and, just as plainly, what they didn't.
The short version
Wegovy (semaglutide), Mounjaro (tirzepatide) and Saxenda (liraglutide) are all built around a gut hormone called GLP-1 (glucagon-like peptide-1). Your body already makes GLP-1 after you eat. It's part of how a meal tells your brain "that's enough." These medicines are engineered versions of that hormone (or, for tirzepatide, that hormone plus its cousin GIP) that last far longer than the natural version, so the "that's enough" signal stays switched on rather than fading within minutes of finishing a meal.
Where these medicines act: gut, pancreas, brain
GLP-1 is normally released by cells in your small intestine and colon within minutes of eating, then broken down almost immediately by an enzyme called DPP-4. GLP-1 receptor agonists are modified to resist that breakdown, so a single dose keeps GLP-1 receptors switched on for far longer than the native hormone ever manages. Those receptors sit in three places that matter for appetite and weight:
- The stomach. GLP-1 receptor activity slows gastric emptying. Food sits in the stomach longer, so you feel full on less and stay full for longer.
- The pancreas. It increases insulin release and reduces glucagon when blood glucose is high, which is the mechanism these medicines were originally built on for type 2 diabetes.
- The brain. GLP-1 receptors in the hypothalamus and brainstem, the areas that regulate hunger and reward, are activated directly and through the slower gut signalling, turning down hunger drive and food reward at the same time.
Tirzepatide (Mounjaro) adds a second hormone receptor to that list: it's a dual GIP/GLP-1 receptor agonist. GIP (glucose-dependent insulinotropic polypeptide) is another gut hormone released after eating, and activating both receptors together appears to produce a stronger effect on appetite and body weight than activating GLP-1 receptors alone. Exactly why adding GIP receptor activity amplifies the effect is still an active area of research.
What people notice
Put those three sites together and you get three effects people commonly report:
- Slower gastric emptying. Meals move through the stomach more slowly, so a normal-sized plate produces a fuller feeling that lasts longer between meals.
- Stronger fullness signalling. The brain gets a stronger, more sustained "you've eaten enough" signal, so second helpings and snacking urges are genuinely reduced, not just white-knuckled through.
- Less "food noise." Many people describe a drop in the constant background thinking about food. It isn't a formal clinical term, but it's a consistent theme in how people talk about this class of medicine. See food noise, explained.
The implication: if a medicine changes the hormone signal that governs hunger and reward, the person taking it isn't fighting hunger with willpower any more. The hunger signal itself is turned down. That's a different problem to solve than "try harder."
Weekly vs daily: Wegovy, Mounjaro and Saxenda
All three Medsafe-approved options work on the mechanism above, but they're taken differently because of how the molecule is built:
- Wegovy (semaglutide): once-weekly injection. Same active molecule as Ozempic, which is Medsafe-approved for type 2 diabetes rather than weight management.
- Mounjaro (tirzepatide): once-weekly injection. Dual GLP-1/GIP receptor agonist, as above.
- Saxenda (liraglutide): once-daily injection. An earlier-generation GLP-1 receptor agonist; the shorter-acting molecule is why it needs daily rather than weekly dosing.
All three are started at a low dose and increased in steps over several weeks (titration), so your body can adjust. The pace is set by your prescriber. For how they compare, see Wegovy vs Mounjaro vs Saxenda.
What the trials found
These are large randomised controlled trials, published in peer-reviewed journals. In every one, the medicine was given alongside diet and activity support, not instead of it.
Around 15% average body-weight reduction over 68 weeks
A randomised, double-blind, placebo-controlled trial in 1,961 adults with overweight or obesity, all receiving lifestyle intervention. In this clinical study, mean body-weight change was −14.9% on semaglutide against −2.4% on placebo at week 68.
Honest note: these are group averages. The spread around them is wide. Some participants lost a great deal more, and some lost little. An average is not a forecast for you.
Wilding JPH et al., New England Journal of Medicine 2021;384:989–1002 (STEP 1).
Around 21% average body-weight reduction over 72 weeks
A randomised, double-blind, placebo-controlled trial in 2,539 adults, again with lifestyle support throughout. In this clinical study, mean body-weight change on the highest dose tested was −20.9% against −3.1% on placebo at week 72. Lower doses produced smaller average reductions.
Honest note: the two trials above ran in different populations at different times, so the headline percentages are not a like-for-like race between the medicines. Which one suits you, if either does, is a prescriber's judgement, not a league table.
Jastreboff AM et al., New England Journal of Medicine 2022;387:205–216 (SURMOUNT-1).
The part the ads leave out: stopping
When treatment stops, weight tends to come back
The same programmes tested what happens when treatment comes off. In STEP 4, participants who continued treatment after week 20 lost further weight, while those switched to placebo regained weight over the following 48 weeks. In the STEP 1 extension, participants who came off treatment regained around two-thirds of the weight they had lost within a year.
Why this matters: a script on its own is a temporary result. What holds is the habits and the support built around the medicine, which is the part of this that isn't a medicine, and the part a membership can help with.
Rubino D et al., JAMA 2021;325:1414–1425 (STEP 4). Wilding JPH et al., Diabetes, Obesity and Metabolism 2022;24:1553–1564 (STEP 1 extension).
Studies of tirzepatide's withdrawal (SURMOUNT-4) point the same way: the effect lasts while treatment continues, not after it stops. Any decision about reducing or stopping a medicine is one to make with your prescriber.
What the evidence shows, and what it doesn't
Both columns matter. Decide on what has actually been demonstrated, not on what an advertisement implies.
| What the evidence shows | What it doesn't |
|---|---|
| Shown: large average reductions in body weight over 68–72 weeks in big randomised trials, against placebo. | Not shown: that you will get the average. Trial results are group means with a wide spread, and some participants respond very little. |
| Shown: the effect holds while treatment continues, and continued treatment produced further loss in STEP 4. | Not shown: that it lasts after stopping. The withdrawal studies point the other way: most of the loss came back. |
| Shown: every trial delivered the medicine with diet and activity support. That is the tested combination. | Not shown: that the medicine works as well on its own. No large trial tested it without lifestyle support. |
| Shown: a well-characterised side-effect profile. Gastrointestinal effects such as nausea, vomiting, diarrhoea and constipation are the most common, usually mild to moderate, mostly early and dose-related. | Not shown: that it is suitable for everyone. There are real contraindications and cautions, and serious adverse effects occur. Only a prescriber can weigh them for you. |
| Shown: Medsafe has approved these medicines for chronic weight management in New Zealand. | Not the same thing: approved is not funded. Pharmac does not fund them for weight management, so they are paid for privately. |
Medicine is one lever, not the whole plan
Turning down hunger signalling doesn't automatically build the habits that keep weight off. Movement, sleep, food choices and eating patterns still do the structural work. What the medicine does is remove the constant hunger pressure that makes those habits hard to start. NZSSD (New Zealand Society for the Study of Diabetes) guidance and recognised endocrinology practice both treat medicine as an adjunct to, not a replacement for, lifestyle change in obesity management.
Benefits and risks: these are prescription medicines
Wegovy, Mounjaro and Saxenda are prescription-only medicines in New Zealand. They have real benefits (weight loss and metabolic improvements are the reason they're approved) and real risks. The most common side effects are nausea, constipation and other gastrointestinal effects, especially early in treatment, and there are less common but more serious risks set out in each medicine's data sheet. Whether one of these medicines suits you depends on your health history, current medicines and weight-related health risk. A New Zealand-registered prescriber makes that call with you, not this page.
Frequently asked questions
Do I need to have diabetes to be prescribed one of these?
No. Wegovy and Mounjaro are approved in New Zealand for weight management in adults with obesity, or overweight with a related health condition, whether or not they also have type 2 diabetes. Saxenda is used the same way. A prescriber confirms which category you fall into from your history.
Is this the same thing as Ozempic?
Ozempic and Wegovy share the same active ingredient, semaglutide, but Ozempic is Medsafe-approved for type 2 diabetes, not weight management. See how to get Ozempic or Wegovy in NZ.
Do I still need to change how I eat?
Yes. The medicine lowers hunger pressure; it doesn't replace food choices, movement or sleep. Every trial above tested it alongside those, not instead of them. See foods to eat and foods to go easy on.
What happens if I stop taking it?
The hormone signal fades once the medicine clears your system, and hunger typically returns towards where it was. In the withdrawal studies above, most people regained much of the weight they had lost. Talk to your prescriber before stopping.
How is my starting dose decided?
Doses are started low and increased over time under a prescriber's supervision, following the schedule in each medicine's data sheet. Your prescriber sets the pace.
See whether this could suit you
A free 3-minute check. No payment to start. Whether any medicine is appropriate is always a prescriber's decision.
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