Dr Nick Fuller
Leading Obesity Expert at the University of Sydney and founder of Interval Weight Loss.
New weight loss medications like semaglutide, an injectable drug originally developed for type 2 diabetes, are gaining attention as a treatment option for managing obesity.
Supporters, including some well-known names, say it can help reduce appetite, support weight loss, and make it easier to maintain a lower weight. But while early results are encouraging, it’s important to look at the full picture, and for many people, one practical question often comes up: do the injections actually hurt?
A 2021 study found that participants using semaglutide lost an average of 14.9% of their body weight over 68 weeks, which is much more than those using lifestyle changes alone. That’s promising, but semaglutide isn’t a simple, one-and-done solution. It’s a weekly injection, and for those new to self-administering medication, that might feel a bit daunting.
To answer that question, we need to consider where the injection goes, what side effects are common, and what can trigger or ease discomfort at the site. Read on to learn what to expect and how to make the experience as comfortable as possible.
Semaglutide is injected under the skin. This is called a subcutaneous injection, which means it goes into the fatty layer just beneath the skin, not into muscle or a vein.
The most common injection sites are:
The abdomen (at least 5 cm away from the belly button)
The front of the thighs
The upper arms
There’s no single site that works best for everyone. It mostly comes down to what feels most comfortable and accessible. Some people find the abdomen easier to manage, while others prefer the thighs because the skin feels less sensitive.
Rotating your injection site is important. Repeatedly using the same spot can lead to irritation or lumps under the skin. This can affect how well your body absorbs the medication, so even if you have a go-to spot, try to switch it up regularly.
Like any medication, semaglutide can cause side effects. Most are mild and tend to ease over time as your body adjusts, particularly during the first few weeks or dose increases.
As mentioned earlier, the 2021 study on semaglutide’s effects on weight loss also reported gastrointestinal symptoms as the most common side effects during treatment. Other large trials, including the STEP 2 trial and SUSTAIN 7 study, support this pattern.
Here’s what you’re most likely to encounter:
Nausea
Nausea is the most frequently reported side effect. In one clinical trial, it affected about 36.6% of participants taking semaglutide. Eating smaller meals and avoiding high-fat or spicy foods can help reduce the discomfort.
Vomiting
Vomiting tends to occur alongside nausea. Participants across multiple studies reported this symptom, particularly at higher doses or during the first month of treatment. If it’s persistent or severe, your doctor may recommend pausing or reducing the dose before gradually increasing again.
Diarrhoea
Diarrhoea was reported in 29.7% of participants taking semaglutide 2.4?mg in pooled analyses from the STEP 1–3 clinical trials. According to the SUSTAIN trials, this usually resolves on its own, but bland, low-fibre meals and proper hydration can help manage it in the short term. If dehydration becomes an issue, adding an oral rehydration solution can be helpful.
Constipation
Constipation is another common symptom. In a real-world analysis of over 10,000 GLP-1 receptor agonist users, constipation was reported in approximately 30% of participants. Adding more fluids and gentle dietary fibre may help ease this. It can also help to stay active, as regular movement supports healthy digestion.
Headache
Headaches appear less frequently but still affect a number of users. They may be related to shifts in blood sugar or fluid intake. While generally mild, persistent headaches should be discussed with your GP. Drinking enough water and ensuring consistent meals can make a noticeable difference.
Fatigue
Feeling unusually tired or low on energy can occur, especially in the early stages of treatment. This may be related to reduced calorie intake or mild dehydration. It often settles as your body adjusts, but if it persists, it’s worth checking for other possible causes like iron or B12 deficiency.
Dizziness
Light-headedness is occasionally reported, especially if meals are skipped or fluid intake is low. Eating regularly and staying well hydrated may reduce the likelihood of this symptom. If dizziness continues, checking your blood pressure or glucose levels can help identify the cause.
Stomach pain
Mild abdominal pain or cramping was noted in several studies. It’s often short-lived and resolves as the digestive system adapts to the medication. Keeping meals light and avoiding lying down immediately after eating may help ease discomfort.
While side effects can be off-putting at first, they are usually manageable and temporary. If any of these symptoms persist or interfere with daily life, it’s worth speaking to your doctor. Sometimes, adjusting the dose or how quickly it's increased can make all the difference.
Redness, swelling or stinging after an injection can happen for a few reasons. These site reactions aren’t uncommon with injectable medications, and they’re not always caused by the drug itself. What might be causing the irritation? It often comes down to a few key variables.
Semaglutide is suspended in a solution that includes buffers and stabilisers. While essential for preserving the drug’s potency, these components can occasionally irritate the surrounding tissue, especially in individuals with more sensitive skin.
The way the injection is administered can influence how the body reacts. Injecting too quickly, applying excessive pressure, or using the same area repeatedly may increase the likelihood of bruising or tenderness.
Injecting semaglutide while it’s still cold from the fridge can cause a sharper sting. Allowing the medication to reach room temperature, typically about 30 minutes, is a simple step that may make the process more comfortable.
Residual alcohol from skin prep can contribute to a stinging sensation if not fully dried before injection. Even a small amount carried under the skin by the needle can cause irritation.
Some individuals are simply more prone to skin reactions. Factors like thinner tissue, immune response, or even stress levels can influence how the skin and underlying tissue respond to a subcutaneous injection.
Injection site reactions can be uncomfortable but are usually manageable with a few simple steps. While everyone's body reacts differently, here are some basic strategies that can help calm the skin and reduce irritation:
Use a cold compress on the injection site: Applying a clean, cold pack for 10–15 minutes may help ease swelling and soothe the area.
Switch injection spots each time: Rotating between approved injection sites, like the abdomen or thigh, can reduce the risk of repeated irritation in one area.
Apply a mild anti-itch cream: A fragrance-free, over-the-counter hydrocortisone cream may help relieve itchiness, but check with your pharmacist or doctor first.
Keep the area clean and dry: Washing your hands before injecting and gently cleaning the skin can help prevent infection or lingering residue that may aggravate the skin.
Avoid rubbing or scratching the site: It’s tempting, but touching the area too much can make irritation worse or introduce bacteria.
Talk to a doctor if the swelling gets worse: If the redness, pain or swelling doesn’t settle or starts to spread, it’s best to check in with your GP to rule out any complications.
Semaglutide is a promising tool in the treatment of obesity, but like any medication, it comes with practical considerations, including how it feels to take. Most people find the injections manageable, and with the right preparation, discomfort at the site can often be reduced or avoided altogether.
Knowing where and how to inject, recognising common side effects, and knowing what might trigger a reaction puts you in a better position to make semaglutide work for you, if it’s the right treatment path.
As always, speak to your doctor if you’re unsure how to manage symptoms, or if injection pain becomes persistent. And if you're exploring whether semaglutide aligns with your long-term health goals, keep reading. The more informed you are, the better the choices you can make.
Curious how semaglutide compares to other weight?loss injections? Dive into our in?depth guide Are Weight Loss Injections Safe? What You Need to Know Before You Start to understand potential side effects, who’s eligible and how pain expectations stack up.
Dr Nick Fuller is the founder of Interval Weight Loss and is a leading obesity expert at the University of Sydney with a Ph.D. in Obesity Treatment. Dr Fuller is also the author of three best-selling books and his work been published in top ranked journals in the medical field, including JAMA, Lancet and American Journal of Clinical Nutrition.