What to expect from your first dose of Wegovy

What the clinical evidence says about semaglutide side effects at the start of treatment

The STEP 1 trial, published in the New England Journal of Medicine, enrolled 1,961 adults and remains the cornerstone evidence base for Wegovy's side-effect profile. Gastrointestinal effects were the most frequent adverse events across the whole trial, but they were heavily front-loaded. Participants reported nausea most often during the dose-escalation phase, with rates falling substantially once a stable dose was reached. This pattern isn't incidental: the semaglutide dose schedule was specifically designed around it, starting at 0.25 mg to reduce GI burden before stepping up every four weeks.

The NHS semaglutide medicines page lists the common reactions (affecting more than one in ten people) as nausea, vomiting, diarrhoea, constipation and headache. Less common effects include fatigue, dizziness, burping and indigestion. Injection-site reactions (mild redness or itching where the pen was used) are also reported, though these tend to be minor and brief. None of this should be read as a reason to avoid starting; it should be read as the reason the titration schedule exists. Your system needs a run-in period, and most people find the first few weeks the hardest.

One thing worth knowing: reactions to the 0.25 mg starting dose are typically milder than what some people encounter later at higher strengths, simply because the drug concentration is lower. For many patients the first injection produces little more than mild queasiness for a day or two.

The side effects people actually notice in the first 48 hours

Nausea usually begins a few hours after the injection and tends to peak somewhere in the first 24 hours. It can range from a background unease that doesn't interfere with eating to genuine nausea that makes mealtimes unappealing. Vomiting does occur, though it is less common than nausea at the starter dose. Loose stools or constipation are both possible, the two can alternate in the same person in the same week, which is disorienting if you're not expecting it.

Fatigue and mild headache on the day after injecting are reported by a meaningful minority of new starters. These generally ease within 48 hours. Eating smaller, lower-fat meals in the day of and after the injection can reduce how pronounced the GI effects feel. Staying well hydrated matters too, particularly if diarrhoea is present, because dehydration can compound the tiredness.

The injection itself deserves a brief note. Wegovy arrives in a pre-filled pen, and the 0.5 mg pen you'll use four weeks later looks almost identical. When your first treatment arrives (tracked by DPD, in plain unbranded packaging) the pen goes straight into the fridge. Most people find the injection itself unremarkable: the needle is short and fine, and the injection sites (abdomen, thigh or upper arm, rotated each week) are ones you can reach without difficulty. Injection-site soreness, if it appears at all, is usually gone within a day.

When to get medical help, and what cannot wait

Most first-dose side effects are uncomfortable rather than dangerous. But some symptoms are signals to seek help quickly, and it matters to know the difference before you inject for the first time.

Severe, persistent stomach pain (particularly pain that spreads to the back or comes with persistent vomiting) should prompt urgent medical attention. In January 2026 the MHRA issued a Drug Safety Update specifically highlighting acute pancreatitis as a known, if infrequent, risk with GLP-1 medicines; the guidance is clear that this kind of pain should not be managed at home while waiting to see whether it settles. Call 111 or attend an emergency department. You can also flag the experience to the MHRA's Yellow Card scheme, which collects safety data from patients directly, every report contributes to the ongoing safety monitoring of these medicines.

Other symptoms that warrant prompt attention: signs of an allergic reaction (swelling of the face, lips or throat; difficulty breathing; a widespread rash), symptoms of gallbladder problems (sudden severe pain in the upper right abdomen, often after eating), and signs of significant dehydration from vomiting or diarrhoea (very dark urine, dizziness on standing, inability to keep fluids down). If your mood dips noticeably or you have any thoughts of self-harm in the weeks after starting, speak to your GP or call 111, this is listed as a possible side effect to monitor. None of these are common, but knowing the list means you won't dismiss something that needs attention. The side-effect profile at higher doses is broadly similar, but intensity can increase with dose, another reason escalation is gradual.

How suitability and side effects are assessed at nume before treatment starts

Wegovy is a prescription-only medicine. The only legal route to it in the UK is a prescription following a clinical assessment, and that assessment is where side-effect risk should first be discussed. At nume, every consultation is personally reviewed by a GPhC-registered Independent Prescriber, not routed through automated software. Your answers are read by a clinician the same day.

That review covers medical history, current medicines and any factors that would make semaglutide unsuitable, including a history of pancreatitis, medullary thyroid carcinoma or MEN2, and pregnancy or breastfeeding (semaglutide is not recommended in any of these situations). It also covers medicines that interact with GLP-1 treatment, so any concerns about your specific circumstances are identified before a prescription is issued, not after your first injection. If you have questions about how the treatment affects your body during the earlier dose stages, our pages on what to expect from the 1 mg dose and on whether Wegovy affects liver enzyme levels cover both topics in detail. If you want to understand more about the full treatment picture before deciding, our weight-loss treatment overview sets out the options, and our prescribers discuss suitability and side effects as a standard part of every consultation. Check your eligibility to begin.