The first injection is the smallest dose of the whole schedule, given under the skin of the abdomen or thigh, once, and then you wait a week. That is genuinely most of it. What this article does not contain is the step-by-step for operating your particular pen, and the reason for that is in the section below rather than buried in a disclaimer.
Instructions for Use: the device leaflet packed with the pen itself, separate from the prescribing information. It is written for the exact presentation you were dispensed, which is why it beats any general article, including this one.
Why the first dose is the smallest one
Because the schedule is built to start low and go up slowly, deliberately.
GLP-1 medication is not started at the dose it is intended to reach. It begins at a low starting dose and steps up over weeks, and the labels state the escalation is there to reduce the risk of gastrointestinal reactions (label). That means the first injection you give yourself is the gentlest one you will give.
The specific doses and the interval between steps come from your prescriber and your leaflet, not from an article — they differ between medicines and between people. How dose titration works explains the principle and why the ramp exists.
Where it goes, and choosing a day
Abdomen or thigh, weekly, on a day that suits you.
Both labels name the abdomen and the thigh. They differ on the upper arm: semaglutide's names it as a site you can use yourself (label), while tirzepatide's states the back of the upper arm is for someone else to administer (label).
On timing, the labels are more relaxed than people expect. The medicine is taken once weekly, on the same day each week, at any time of day, with or without meals — and the label states explicitly that the time of day and the injection site can both be changed without any adjustment to the dose (label). Both instruct rotating the site with each dose.
So pick a day you will remember. Many people choose one where they are at home and unhurried, which is a preference rather than a clinical requirement. The site detail and the clearance from the navel are in injection sites, storage and travel.
The step that is not in this article
How the pen itself is prepared and fired.
This is not an oversight and it is not caution for its own sake. Pens genuinely differ — between the two medicines, between single-dose and multi-dose presentations, and between versions of the same product. The sequence, what you are meant to see or hear, and how long the pen stays against the skin are not the same across them.
An article that gave you one version of those steps would be right for some readers and wrong for others, and a reader who followed us instead of the leaflet in their own box would be following the wrong instructions for the device in their hand. That is a safety problem rather than a style choice, which is why the line is drawn here.
What to do instead is unglamorous and works: read the Instructions for Use that came with your pen, and ask your prescriber or pharmacist to watch you do it once. Being shown once by someone who can see your actual device is worth more than any written description of it.
What it is likely to feel like
Less than most people expect, on the numbers that exist.
In the weight-management trials, 1.4% of people reported a reaction at the injection site against 1% of people injecting placebo (label). What the trials never recorded is a description of the sensation, so nobody can honestly tell you what it feels like — including us.
The hours and days after the first dose
The effects that show up are usually digestive rather than at the injection site.
For tirzepatide, the reactions reported in 5% or more of patients include nausea, diarrhoea, vomiting, constipation, abdominal pain and indigestion, alongside injection site reactions, fatigue, hypersensitivity reactions, belching, hair loss and reflux (label). The labels instruct escalating the dose gradually to reduce the risk of gastrointestinal reactions, which is part of why the schedule starts low (label).
When they start, how long they last and how bad they get vary between people, and no trial average predicts an individual. GLP-1 side effects covers what is common and what settles, and managing nausea covers the most frequent one.
What is worth having ready
Not much, and none of it is special equipment.
Somewhere to put the used pen or needle afterwards is the one thing people are most often unprepared for, and it is worth asking your prescriber or pharmacist what they want you to do with it before your first dose rather than after. Practice on disposal differs between clinics and between countries, so this is a question for the people who dispensed your medicine rather than for a general article.
Beyond that: the leaflet, somewhere you can sit down, and a few unhurried minutes. Some people find it easier not to make an occasion of it. Others prefer to do the first one with someone else in the room. Neither is clinically better than the other.
What warrants a call in the first week
Two lists exist and neither is restated here, because splitting them across pages is how they get misremembered.
For anything at the injection site — a mark that is spreading, increasing pain, warmth, fever or pus — see bruises, marks and lumps.
For anything else — severe abdominal pain, persistent vomiting, signs of an allergic reaction — see red flags on GLP-1, which is the page that covers the rest of the body.
If something worries you and it is not on either list, that is still a reason to contact the person who prescribed it. A question that turns out to be nothing is a normal part of the first month, not an imposition.
If you have not started yet and are reading this to decide, you can check your eligibility and speak to a doctor about whether this is suitable for you.
Common questions
Can I inject myself, or do I need a nurse?
Both medicines are designed for self-injection at home, and the registered labels describe self-injection sites (semaglutide, tirzepatide). How your particular pen is prepared and used comes from the leaflet packed with it, and asking your prescriber or pharmacist to watch you do it once is a reasonable request.
Where should the first injection go?
The abdomen or the thigh for both medicines. The upper arm is treated differently by each — semaglutide names it as a self-injection site (label), while tirzepatide states the back of the upper arm is for another person to administer (label).
What time of day should I inject?
The registered labels state it is taken once weekly at any time of day, with or without meals, and that the time of day and the injection site can be changed without adjusting the dose (label).
Will the first dose make me feel ill?
The common effects are usually digestive rather than at the injection site. For tirzepatide, nausea, diarrhoea, vomiting and constipation are among the reactions reported in 5% or more of patients, alongside several others (label). What happens to any individual is not predictable from a trial average.
Why doesn't this article tell me how to use the pen?
Because pens differ, and a general instruction that contradicted the leaflet in your box would be a safety problem rather than an inconvenience. The leaflet is written for the exact presentation you were dispensed.