Applies to anyone starting one Always
glp1-practicalitiesFewer than 5 people have reached this rule so farWeight returns on stopping (two-thirds within a year); 25–40% of loss is muscle; GI effects near-universal
No clinician has signed off this rule yet. It reflects our reading of the guidelines cited below, which has not been independently checked.
Word for word, as generated for the example person below. Figures in the text are theirs.
If you stop, the weight comes back. Plan for this as a long-term medication, not a course of treatment.
In the STEP 1 extension, people who had lost 17.3% of their body weight over 68 weeks regained about two-thirds of it within a year of stopping — and the improvements in blood pressure and lipids went with it. That is not a failure of willpower; it is what the drug does and stops doing. The practical consequence is that the decision to start is a decision about years, and the cost and supply questions belong in that conversation from the beginning rather than at the point you run out.
Outcome-provenTested in randomised trials measuring heart attacks, strokes, or death, not a stand-in for them.· Level B-R· checked 2026-09-12
STEP 1 trial extension — weight regain after semaglutide withdrawal · Expect to continue
Between a quarter and two-fifths of what you lose will be muscle unless you actively defend it. Protein and resistance training are not optional extras here.
This is the least-discussed consequence of rapid weight loss on these drugs, and it matters most if you are over 60, where muscle is already being lost to age. The countermeasures are unglamorous and effective: hit a protein target of roughly 1.6 g per kg of body weight daily, and lift something twice a week from the day you start rather than after you notice. Losing fat while keeping muscle is a different outcome from simply weighing less, and only one of them is unambiguously good for you.
Surrogate endpointMeasured as a change in a scan or a lab value, not in events. Usually a smaller trial, and a step removed from what you care about.· checked 2026-09-12
Adverse effects of GLP-1 receptor agonists — 2026 safety review · Practical guidance
The side effects worth knowing: nausea and constipation are near-universal and fade; a handful of rarer problems are worth recognising early.
Gastrointestinal effects — nausea, vomiting, constipation, diarrhoea — affect most people, are worst while the dose is being increased, and are the commonest reason for stopping. Slower titration usually solves it. The less common but more important ones: gallstones (rapid weight loss causes them regardless of the drug), acute pancreatitis at roughly 0.2% in trials, and genuinely severe gut slowing that can persist after stopping. Two newer signals are being watched rather than settled — a rare association with a form of sudden vision loss called NAION, and enough cases of aspiration under anaesthesia that you should tell any surgeon or endoscopist that you take one, well before the day. Fears about thyroid cancer and suicidal thoughts have both been substantially de-risked by the larger 2025-2026 datasets.
Outcome-provenTested in randomised trials measuring heart attacks, strokes, or death, not a stand-in for them.· Level B· checked 2026-09-12
Adverse effects of GLP-1 receptor agonists — 2026 safety review · Safety
Promising evidence that hasn't become standard care yet — worth knowing, not yet worth expecting.
The newer agents lose substantially more weight than semaglutide. None of them has shown it prevents a heart attack.
Retatrutide, which hits three receptors at once, produced about 28% mean weight loss at 80 weeks in phase 3 and around 30% by two years — roughly double semaglutide. CagriSema, semaglutide combined with an amylin analogue, reached about 23%. Orforglipron, approved in April 2026, is the first daily oral drug in this space and removes the injection entirely. All of that is real and it is genuinely a different era of obesity treatment. But weight loss is not the endpoint you care about, and the cardiovascular outcome trials for these agents have not reported. Semaglutide remains the only one with proof it prevents events in people without diabetes, and more weight lost does not automatically mean more events prevented — that inference is exactly the one that has failed before.
Surrogate endpointMeasured as a change in a scan or a lab value, not in events. Usually a smaller trial, and a step removed from what you care about.· Level B-R· checked 2026-09-12
Next-generation incretin agents — phase 3 results through 2026 · Weight-loss evidence only — no outcome data yet
“Diabetes, already on a statin” — an illustrative profile, not a real user.
Asked after: BMI 27 or above, or type 2 diabetes
Cited by the recommendations above.
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Runs in lib/engine/glp1Pathway.ts as glp1-practicalities.