You will be handed a pen, a box of needles, and roughly ninety seconds of instruction. Most people leave that appointment knowing how to inject and almost nothing about what the next eight weeks will feel like.
This is the account I give my own patients before they start. It is general, and it is not a substitute for the person who actually knows your history — but it covers the questions that come up in week two at eleven at night.
Week one: the dose that isn’t meant to work
Every GLP-1 protocol starts below the therapeutic range. Semaglutide begins at 0.25 mg weekly; tirzepatide at 2.5 mg. Neither dose is expected to produce meaningful weight loss, and that is the point. The starting dose is a tolerance-building exercise, giving the gastrointestinal tract four weeks to adapt to slower emptying before the dose climbs.
People who do not know this often conclude in week three that the drug “isn’t working” and ask to jump ahead. It is the single most common early mistake, and it reliably buys a worse month.
What you may notice instead is subtler: meals ending sooner than expected, a plate half-finished without a decision having been made about it, and — the phrase almost everyone uses eventually — the food noise going quiet.
Weeks two to four: appetite, and the strangeness of it
The reduction in appetite is not willpower arriving late. GLP-1 receptor agonists act on receptors in the hypothalamus and brainstem that govern satiety, and slow the rate at which the stomach empties. The result is a physiological sense of fullness that arrives earlier and lasts longer.
For many people this is the first time in their adult life that eating has felt optional. That is a larger psychological event than the clinical literature tends to acknowledge, and it is worth expecting rather than being ambushed by.
I keep waiting for the part where I have to fight it. It just hasn’t come.
The practical risk in this window is under-eating rather than over-eating. Appetite falls faster than nutritional need does. Protein intake is the thing to watch — not because protein is magic, but because it is the macronutrient people drop first when they are simply not hungry, and it is the one that protects lean tissue.
Week five onward: the first escalation
The step up — to 0.5 mg semaglutide, or 5 mg tirzepatide — is where side effects most commonly appear or intensify. The pattern is fairly consistent: symptoms cluster in the twenty-four to seventy-two hours after the injection, and are worst after the first dose at a new level.
What is ordinary
Mild to moderate nausea, early fullness, constipation, occasional reflux, fatigue in the first days, and a degree of appetite for food you previously liked simply evaporating. Sulfur-tasting burps are common and harmless, if unpleasant.
What is not
Severe or persistent abdominal pain, especially pain that bores through to the back; repeated vomiting; inability to keep fluids down for more than a day; pain in the right upper abdomen after eating; signs of dehydration. These warrant contact with a clinician rather than a forum.
The things that make the first eight weeks easier
Smaller meals, more of them. Eating slowly enough to notice fullness before you have overshot it. Fluids deliberately, because thirst signals blunt along with hunger. Fiber early, before constipation becomes a problem rather than after. And a plan for protein that does not depend on being hungry.
One more, and it is the one everybody skips: write it down. Injection date, dose, what you ate, and a line on how you felt each of the seven days after. Eight weeks of that turns a bewildering period into a legible pattern — you discover that your bad days are days two and three, every time, and you can start planning around them instead of being ambushed. A notebook does the job. A tracker like Zenday does it better, mostly because it is already on the phone in your hand at the moment the symptom is happening, rather than in a drawer downstairs.
Alcohol tolerance often changes, sometimes markedly. Many people find they simply lose interest, which is one of the more interesting unexplained effects of this class.
A baseline blood panel before or early in this window makes everything later interpretable — see bloodwork on a GLP-1. It is also the point at which sleep often gets briefly worse before it gets better: sleep on a GLP-1.
Almost everything in this window is easier if the fortnight beforehand was used well — the preparation checklist is in how to start a GLP-1, and the complete symptom directory is in every side effect ranked.
What to expect on the scale
Weight loss in the first eight weeks is generally modest and highly variable, because most of that period is spent below therapeutic dosing. The trajectory that matters is measured in months, not weeks, and the trials that produced the headline figures ran for over a year at full dose.
Judging the drug at week eight is like judging a marathon at mile three. Where the ladder goes from here is set out in the GLP-1 dose charts, and what a genuine stall looks like much later is in why weight loss stalls.
When to call
Call if you cannot keep fluids down, if pain is severe, if you are vomiting repeatedly, or if something feels wrong in a way this article does not describe. Clinicians would far rather hear from you in week two about something that turns out to be nothing than in week six about something that did not.
Two practical things are worth getting right early, because they cause more avoidable misery than the drug does: where and how you inject, and drinking enough to protect your kidneys. Building the plate around protein from week one is the third — see what to eat on a GLP-1.
And call, too, if the side effects are merely tolerable but relentless. Titration schedules are not laws of physics. Staying at a dose longer, or moving up more slowly, is a legitimate and frequently better plan.