Medical weight loss gets talked about a lot right now, and that can feel a bit noisy if you are trying to make a careful decision.
Side effects tend to be the part that people worry about most, and honestly, that worry is usually reasonable.
This article looks at what we currently know about side effect profiles for orforglipron and semaglutide, with a focus on safety, day-to-day tolerability, and what people often notice early on.
Because these medicines sit in a regulated space, this is general information, not a suggestion that either option is right for you. A medical professional, such as one of our pharmacists, still needs to check your health history, current medicines, and risk factors before any prescription is considered.
Common side effects of orforglipron
Orforglipron is an oral, small-molecule GLP-1 receptor agonist that has been studied in clinical trials and described in medical literature as investigational.
In published trial reporting so far, the most frequently reported side effects have been gastrointestinal, which is very typical for GLP-1 medicines as a group.
What people most often report includes:
- Nausea
- Diarrhoea
- Vomiting
- Constipation
- Sometimes, indigestion or dyspepsia
In a Phase 3 programme report, involving adults with type 2 diabetes, rates for some gastrointestinal effects were reported in ranges across doses, with diarrhoea and nausea among the more frequent effects, and vomiting reported less often.
It is also worth saying, plainly, that orforglipron is not yet a routinely available, licensed option in the UK for weight management at the time of writing. The evidence base is still building, and real-world tolerability data remains limited compared with older GLP-1 options.
Common side effects of semaglutide
Semaglutide is a prescription-only GLP-1 medicine that has been studied in large trials for weight management, and its side effect profile is widely described in peer-reviewed literature.
Like orforglipron, the most common issues reported are gastrointestinal, and they tend to cluster in the first weeks, especially as doses increase.
Effects people often report include:
- Nausea, which is the one many people mention first
- Diarrhoea
- Vomiting
- Constipation
- Bloating or abdominal discomfort
- Reduced appetite, which can feel like a side effect if it is intense
Across STEP trials and related analyses, gastrointestinal events were commonly described as mild to moderate and often transient. Some people do stop treatment, though, because symptoms do not settle.
Gastrointestinal side effects compared
This is the part people usually want, a straightforward comparison, yet it is still not a straight fight because trials differ in design, dose schedules, and patient groups. The table below is a “what shows up most often” view, not a declaration that one option is better.
| Symptom | Orforglipron (trial reporting so far) | Semaglutide (trial reporting) |
| Nausea | Commonly reported | Commonly reported |
| Diarrhoea | Commonly reported | Commonly reported |
| Vomiting | Reported, often less frequent than nausea | Reported, sometimes during escalation |
| Constipation | Commonly reported | Commonly reported |
| Appetite suppression | Can occur, varies person to person | Can occur, varies person to person |
One practical point is that tolerability often depends on how quickly the dose is increased, your usual eating pattern, and whether you are prone to reflux, constipation, or migraines anyway.
Severity and duration of side effects
With GLP-1 medicines, side effects often feel most noticeable during dose titration, meaning the step-by-step increase phase.
Many people find symptoms ease after a few weeks at a stable dose, yet some people continue to have nausea or bowel changes and need a slower plan, a dose reduction, or a stop.
If you are comparing experiences online, it helps to remember that one person’s “two rough weeks” might be another person’s “I had to stop”, and both can be true.
Side effects during dose increases
Gradual dosing is used because it can make gastrointestinal side effects less intense for many people.
A clinician might advise holding a dose for longer if symptoms are lingering, which can be a calmer way to judge whether your body is adjusting or whether it is simply not tolerating the medicine.
This is also why a proper consultation matters, because the dosing plan is part of the safety picture, not a small detail.
Long-term safety considerations
Most conversation focuses on nausea, yet longer-term safety is where clinicians pay close attention, especially if you have other risks.
Across GLP-1 medicines as a class, rare but serious risks discussed in medical sources include gallbladder problems and pancreatitis. The usual advice is to assess symptoms quickly rather than waiting them out.
Longer-duration semaglutide trial data continue to describe gastrointestinal events as the most common category overall, with serious events being less frequent. Monitoring and good clinical follow-up still matter.
For orforglipron, longer-term real-world data is still emerging, so ongoing trials and post-authorisation safety monitoring will shape what clinicians can say with more confidence over time.
Managing side effects effectively
If you do experience gastrointestinal side effects on a GLP-1 medicine, there are a few steps that, in practice, tend to help.
- Eat smaller meals, and more slowly than you think you need to
- Avoid very fatty or very spicy foods during titration, as they can make nausea or reflux worse
- Keep fluids steady across the day, especially if diarrhoea shows up
- Prioritise fibre gently, because constipation can sneak up when appetite drops
- Avoid large late-night meals, as this can aggravate heartburn and nausea
- Tell your clinician early if symptoms are stopping you from eating or drinking properly, because that is usually the point where the plan needs adjusting
If you are exploring options through WePrescribe, you can read more about the general category of support on our weight loss medication page.
When side effects require medical advice
Most side effects settle, yet some symptoms need prompt clinical input.
Seek medical advice urgently if you have:
- Persistent vomiting, especially if you cannot keep fluids down
- Severe abdominal pain, particularly if it is new, worsening, or radiates to the back
- Signs of dehydration, such as dizziness, very dark urine, or confusion
- Ongoing severe diarrhoea that is not improving
If you want help understanding whether a GLP-1 medicine is a reasonable option for you, and what side effects might look like in your specific situation, speak to one of our qualified pharmacists here at WePrescribe via our contact us page.
