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Your first week on semaglutide is usually quieter than you’d expect. Your appetite fades a little, you might have some nausea, and almost nothing happens on the scale. That’s by design. The 0.25 mg starter dose is there to let your gut adjust.
Here’s what happens, week by week.
Week one: a small dose, on purpose
Semaglutide starts at 0.25 mg once a week, and tirzepatide starts at 2.5 mg. Both sit at the bottom of a titration ladder, which means the dose goes up a little at a time, about every four weeks. For weekly semaglutide injections, it goes 0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg. (The Wegovy pill is taken daily and has its own starting dose and ladder, set by its label.) The starter dose has one job. It introduces a slower stomach gradually enough that you can keep climbing.
The injection is the easy part. It goes just under the skin of your belly, thigh, or the back of your upper arm, and you switch spots each week. The usual reaction is a small red spot that fades on its own.
Feeling nothing at all for the first few days is normal at this dose. So is finding that dinner ends earlier than you planned.
Appetite quiets before anything else does
Semaglutide acts on the parts of your brain that create hunger, and it slows gastric emptying (how fast food leaves your stomach). Here’s how that feels: your portions shrink on their own, and the background pull toward food turns down. Less appetite is often one of the first effects people notice, though how soon it shows up varies from person to person. If the mental side interests you, we wrote about what happens to food noise on its own page.
What doesn’t change yet is your weight, mostly. More on that below.
Early side effects all have one cause
Every common early side effect comes back to one fact: food sits in your stomach longer. Nausea, reflux, constipation, and early fullness are the mechanical results of slower gastric emptying and eating less. They aren’t signs that something is wrong. They’re usually worst a day or two after your injection and after each dose increase, and they often ease over the following weeks as your gut adapts.
For what helps, what doesn’t, and when symptoms justify slowing the titration, see the GLP-1 side effects guide.
One thing matters a lot here. Severe belly pain, or vomiting you can’t keep up with, is not a normal titration side effect. Call your clinician the same day.
What the labels flag at any dose
These medications carry a boxed warning for thyroid C-cell tumors seen in rodents, and whether that risk applies to humans isn’t known. They’re contraindicated if you or a close relative has had medullary thyroid carcinoma (a rare thyroid cancer) or MEN 2. They call for caution if you’ve had pancreatitis, and they’re not for use in pregnancy. Your intake review screens for all of these before you start.
Why the scale is quiet
The headline numbers didn’t happen at week four. In STEP 1 (Wilding et al., NEJM 2021), which tested brand-name semaglutide (Wegovy) in 1,961 adults, people lost 14.9% of their body weight on average, compared with 2.4% on placebo. That was measured at week 68 on the full 2.4 mg dose of Wegovy. That’s nearly ten times your starter dose, and more than a year in. Week four at 0.25 mg is the bottom rung of that ladder.
In practice, meaningful weight change usually comes later, once your dose steps up over the following weeks. A flat scale in week three doesn’t mean the drug won’t work for you. It means you’re on 0.25 mg.
Week four: the first dose decision
Around week four, the label schedule raises semaglutide to 0.5 mg (or tirzepatide to 5 mg). But the ladder has a slower setting. Both labels allow you to stay on a dose longer when side effects need more time, and staying at 0.25 mg for a few extra weeks is standard practice. It doesn’t mean you failed.
If you miss a dose, follow the instructions for your exact product, or ask your clinician. Missed-dose rules differ between products. Whether you move up at week four is your clinician’s call, and the calendar doesn’t decide it.
At the four-week mark, your clinician is weighing three questions. Is your nausea limited to the days after your injection, or has it become constant? Are you meeting your fluid target most days? Is your protein anywhere close to where it should be? If all three answers look good, the next step is simple. If fluid or protein has slipped, say so before your dose goes up. A dose increase lands on top of whatever is already happening, and that may be a reason to wait one more cycle. You and your clinician make this call together, and it isn’t a test you can fail.
What the first month is really for
The first four weeks are about getting used to the medication. The phase that produces the trial results comes after that, on higher doses, over months. The full picture is in our GLP-1 weight loss guide.
If you’re still deciding whether a GLP-1 fits you at all, start with the online quiz. A clinician reviews every case within 24 hours.
