What semaglutide really does — and what happens when you stop

GLP-1 receptor agonists like Ozempic and Wegovy have attracted more media coverage than almost any health story in recent years — some of it useful, a lot of it hype. Below I walk through what the clinical evidence actually shows: how these drugs work, what the trials measured, the risks you need to weigh, and a genuinely surprising line of research that most coverage misses entirely.

Key Takeaways

  • The landmark STEP 1 trial found weekly semaglutide produced an average 15% body weight reduction over 68 weeks — roughly three times what older weight-loss drugs typically achieved.
  • When participants stopped the drug in the trial extension, they regained about two-thirds of that lost weight within a year; the biology, not willpower, is the reason.
  • Early phase 2 data suggests semaglutide may significantly reduce heavy drinking in people with alcohol use disorder — though it is not approved for this use and phase 3 trials are underway.

What GLP-1 drugs are and how they work

GLP-1 — glucagon-like peptide-1 — is a hormone your gut produces after you eat. It signals to your brain that you’re full, slows how quickly your stomach empties, and helps your pancreas release insulin at the right moment. GLP-1 receptor agonists mimic that signal at a much higher potency and for much longer than the hormone itself manages.

The most widely discussed version is semaglutide, sold as Ozempic for type 2 diabetes management and as Wegovy for weight loss. A newer drug, tirzepatide — sold as Mounjaro and Zepbound — adds a second hormone target called GIP (glucose-dependent insulinotropic polypeptide). That second target appears to push results further: trials of tirzepatide show average weight losses around 20%.

Think of GLP-1 as a volume dial on the biological signal telling your brain a meal is over. These drugs turn that dial up, and hold it there.

What the trials actually measured

The STEP 1 trial enrolled 1,961 adults with overweight or obesity and followed them over 68 weeks. Weekly semaglutide at 2.4 mg produced an average body weight reduction of around 15%, compared with roughly 2% for placebo. To put that in context, most older weight-loss medications averaged somewhere near 5%.

The SURMOUNT-1 trial of tirzepatide showed average reductions approaching 20%, making it the strongest obesity pharmacotherapy data seen to date.

These are averages. Individuals vary, and “average 15%” means some people lost considerably more and some considerably less. The STEP 4 trial also showed that people who continued on semaglutide after an initial weight-loss phase maintained their results — reinforcing that the drug’s effect is active, not a one-time reset.

The risks worth knowing before you start

Side effects are real, and the most common ones — nausea, vomiting, and diarrhoea — tend to hit hardest during the dose-escalation phase as the body adjusts. For most people they ease once the dose stabilises.

There are two more serious risks worth discussing with a doctor before starting.

Medullary thyroid carcinoma. The FDA label for semaglutide carries a black-box warning for this specific type of thyroid cancer. The signal came from animal studies and has not been confirmed in human trial data — but anyone with a personal or family history of medullary thyroid carcinoma, or of MEN 2 (multiple endocrine neoplasia type 2), should not take these drugs.

Gallbladder disease. GLP-1 receptor agonists are associated with an elevated risk of gallstones and related gallbladder problems. The mechanism likely involves changes in how quickly the gallbladder empties.

Neither risk is a reason for everyone to avoid the medication. But both belong in the conversation before you start, not after.

The research most coverage misses: alcohol and the brain

Here’s the distinction that matters: GLP-1 receptors don’t only sit in your gut. They’re also found in the brain’s reward and motivation circuits — the same pathways involved in hunger and, it turns out, in cravings for alcohol.

A 2025 randomised phase 2 trial published in JAMA Psychiatry (Hendershot et al., 48 adults with alcohol use disorder) found that semaglutide significantly reduced heavy drinking days, drinks per drinking day, and weekly alcohol cravings. The effects were large. A 2026 randomised controlled trial in The Lancet (108 participants with alcohol use disorder and comorbid obesity) found robust effects in treatment-seeking individuals.

To be clear: semaglutide is not approved for alcohol use disorder. Phase 3 trials are now underway, and that’s the stage at which these findings either hold up or don’t. The early signal is real, and the underlying biology provides a plausible reason to expect it.

This doesn’t mean GLP-1 drugs are an addiction treatment — that would be getting well ahead of where the evidence sits. What it does mean is that the mechanism of these drugs may reach further into the brain than the weight-loss story implies.

What happens when you stop

Obesity is a chronic, relapsing condition — not a moral failure. GLP-1 drugs treat it like a chronic condition, which means the treatment needs to be ongoing for the effect to persist.

The STEP 1 trial extension followed participants after they stopped semaglutide at 68 weeks. Within a year, they regained approximately two-thirds of the weight they had lost. Hunger hormones rebounded. Appetite returned. The biological signals that drive eating were no longer suppressed.

The weight came back because the drug was gone — not because anyone failed at anything.

A useful way to frame this: think of it like blood pressure medication. It controls blood pressure while you take it. Stopping doesn’t mean the drug failed; it means the underlying condition is still there. The same logic applies here.

That framing shifts the real question. Not whether these drugs work — the evidence is clear that they do — but whether long-term use makes sense for your situation. The cost is real. The weekly injections are ongoing. The risk profile doesn’t disappear. Those trade-offs are worth weighing with full information.

What these drugs can’t do

  • Replace broader lifestyle changes — trial participants received behavioural support alongside medication
  • Cure obesity; they manage it while the drug is active
  • Treat alcohol use disorder — this is not an approved use and phase 3 data is still pending
  • Eliminate side effects or the contraindication profile; those trade-offs are real

When to talk to a doctor

If you’re considering a GLP-1 receptor agonist, that conversation starts with your GP. A personal or family history of medullary thyroid carcinoma or MEN 2 is a hard contraindication. A history of pancreatitis or gallbladder disease warrants careful discussion. So does any situation where ongoing cost or injection tolerance is a genuine barrier.

If you’re managing alcohol use disorder, the current evidence supports waiting for phase 3 results before drawing conclusions — and talking to a specialist about what’s already available and approved.

The Bottom Line on GLP-1 Drugs

The evidence for semaglutide and tirzepatide as obesity treatments is the strongest we’ve seen for any weight-loss medication. A 15–20% average reduction in body weight from a weekly injection is a genuine shift from what came before.

The honest caveat is just as clear: these are maintenance drugs. Stop them and the biology that drives weight regain restarts. That’s not a flaw in the drugs — it reflects how obesity works as a condition. The decision to use them long-term is a real trade-off between sustained benefit and ongoing cost, risk, and commitment. Neither miracle nor nonsense: robust evidence, real limitations.

The alcohol use disorder research is genuinely interesting early-stage science. The biology is plausible and the phase 2 signals are large enough to take seriously — but calling this a breakthrough in addiction treatment would overstate where the science currently sits. Phase 3 will tell us whether the effect holds.

Frequently Asked Questions

Do I need to stay on semaglutide indefinitely to keep the weight off? The STEP 1 extension data suggests that stopping leads to substantial weight regain — roughly two-thirds of lost weight within a year. Whether ongoing use makes sense depends on your situation, risk tolerance, and the practical question of sustained access and cost. This is worth discussing openly with your doctor rather than deciding alone.

Is the thyroid cancer warning on Ozempic something most people should be worried about? The warning applies specifically to medullary thyroid carcinoma — a relatively rare cancer — and the signal came from animal studies rather than human trial data. For most people without a relevant personal or family history, it isn’t a reason to avoid the drug, but it is worth flagging in your initial conversation with your GP before starting.

Can semaglutide help with alcohol cravings? Early phase 2 trial data from 2025 and 2026 suggests it may reduce heavy drinking days and cravings in people with alcohol use disorder — but semaglutide is not approved for this purpose, and phase 3 trials are still underway. If alcohol use is a concern, speak with your doctor about currently approved and available options rather than waiting on emerging research.

References

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