GLP 1 medicines like semaglutide and liraglutide, plus the newer dual agonist tirzepatide, have changed obesity and type 2 diabetes care.
They also come with side effects, and every so often, with genuinely serious complications.
A popular Reddit medicine thread asked a blunt question: what is the worst GLP 1 complication you have seen in practice? The replies are a mix of real clinical disasters and predictable “front line bias” – meaning that ICU, surgery, and emergency clinicians see the worst outcomes by definition.
Below is what keeps showing up in those stories, how it maps to known risks in the medical literature and product information, and what people should watch for.
1. Gallstones, cholecystitis and the messy cascade that can follow
One of the most common “serious but not rare” themes was gallbladder disease after rapid weight loss. The typical sequence described is: significant weight loss, then gallstones, then cholecystitis, then surgery.
Most of the time, surgery is straightforward. Sometimes it is not, and the thread includes examples where a gallbladder operation was followed by major complications like perforation and sepsis.
Those secondary complications are not “a GLP 1 side effect” in the simple sense. They are downstream consequences of a chain of events that started with rapid weight loss and gallstones.
Randomised trial data show GLP 1 receptor agonists are associated with increased risk of gallbladder and biliary disease, especially at higher doses, longer use, and when used for weight loss.
2. Pancreatitis, including the nightmare version
Acute pancreatitis comes up repeatedly in the thread, including ICU level necrotising pancreatitis with long admissions, dialysis, drains, feeding tubes, and multiple procedures. That is the nightmare version.
The hard truth is this: pancreatitis is listed as a warning for these drugs, but causality is complicated.
People who qualify for GLP 1 therapy often already carry pancreatitis risk factors (gallstones, high triglycerides, obesity, alcohol, diabetes).
Rapid weight loss itself is also a pancreatitis risk factor. Still, regulators treat it seriously and ask clinicians and patients to report it.
In the UK, the MHRA has been actively encouraging reporting of suspected pancreatitis with these medicines and has launched additional work to understand who is most susceptible.
3. Dehydration, acute kidney injury, clots, and “domino effect” admissions
A very common pattern in real practice is vomiting, diarrhoea, or inability to keep fluids down, leading to dehydration.
Dehydration can cause acute kidney injury and can also contribute to hypotension, falls, and in extreme cases, thrombosis events in susceptible people.
The MHRA has specifically warned that severe gastrointestinal symptoms can lead to dehydration and serious complications, and that patients should seek medical help if they cannot keep fluids down.
4. Severe constipation, ileus, and bowel obstruction that can turn surgical
GLP 1 medicines slow gastric emptying, and they can slow gut transit more broadly. In the thread, clinicians describe extreme constipation and bowel obstruction, sometimes with perforation and colostomy.
Postmarketing reports for semaglutide (Ozempic) include ileus, intestinal obstruction, and severe constipation including faecal impaction.
These events are still uncommon, but they are real enough that they are in official product information.
5. Aspiration risk during anaesthesia and procedures
This one scares anaesthetists for a reason. If the stomach empties slowly, a patient can follow “nothing by mouth” instructions and still have retained gastric contents. The thread includes reports of aspiration of undigested food at induction.
US product information for semaglutide also notes pulmonary aspiration has occurred in patients receiving GLP 1 receptor agonists undergoing procedures with general anaesthesia or deep sedation.
Perioperative guidance has evolved from blanket “hold it” rules toward risk based management, because many patients can continue therapy safely, while higher risk patients may need modified plans.
If you are on one of these drugs and you are having a procedure, do not guess. Tell the surgical or anaesthetic team exactly what you take and when your last dose was.
6. Eye complications: two different issues people mix together
Diabetic retinopathy worsening with rapid glucose improvement
This is a known phenomenon with rapid glycaemic improvement.
In SUSTAIN 6, semaglutide was associated with an increased rate of diabetic retinopathy complications, largely explained by the magnitude and speed of HbA1c reduction in people with existing retinopathy and poor baseline control, often on insulin.
This is not “semaglutide damages the retina” so much as “fast improvement can transiently worsen retinopathy in higher risk patients,” which has parallels in insulin intensification.
NAION: sudden vision loss signal now recognised by EU regulators
The thread mentions NAION, a rare optic nerve event that can cause sudden, often irreversible vision loss.
The European medicines regulator concluded NAION is a very rare side effect of semaglutide medicines and recommended updating product information.
They also advise that sudden loss of vision or rapidly worsening eyesight needs urgent medical attention and that semaglutide should be stopped if NAION is confirmed.
That does not mean most people are at risk. It means the signal was strong enough to meet the threshold for inclusion in safety information.
7. Hypoglycaemia and DKA risks when insulin is mishandled
One of the more sobering stories in the thread is not a direct toxic effect of the drug. It is human factors. People feel too unwell to eat, then cut insulin inappropriately, and spiral into DKA (especially in type 1 diabetes, where GLP 1 drugs are generally not indicated). Or people chase very low glucose readings and over dose insulin.
This is why clinicians adjust insulin and sulfonylureas carefully when starting GLP 1 therapy, and why nobody should stop basal insulin without a plan.
8. Mood, suicidality, and psychiatric reactions: what regulators say
The thread contains individual reports of mood changes, suicidality, and even mania. Individual cases can be real and still not prove a drug causes the outcome.
Regulators have looked at this closely. The MHRA, EMA, and FDA all concluded the available evidence does not support a causal link between GLP 1 receptor agonists and suicidal or self injurious thoughts and actions, though monitoring continues.
So the blunt take is: people can experience mental health changes while on these medicines, but current large scale safety reviews have not confirmed a causal relationship.
9. Muscle loss and frailty, especially in older adults
A quieter concern that shows up in clinician chatter is sarcopenia.
Any weight loss intervention can reduce lean mass alongside fat mass. In older adults, that can translate into weakness, falls, and loss of independence if they are not protecting muscle with protein and resistance work. This is less “emergency admission drama” and more “slow burn harm” that shows up months later.
10. Pregnancy and “surprise” conceptions
This came up in the thread too.
Fertility can improve with weight loss and improved metabolic health, and some people conceive unexpectedly.
There is also a very practical issue with tirzepatide: delayed gastric emptying can reduce absorption of oral contraceptives, and UK guidance advises additional contraception around initiation and dose escalations.
What to watch for, without turning your life into a panic spiral
Most people do not get the horror story outcome.
The common side effects are nausea, reflux, diarrhoea, constipation, reduced appetite, and fatigue.
The serious stuff is uncommon, but you should know the red flags:
- Persistent vomiting or inability to keep fluids down
- Severe abdominal pain, especially if it radiates to the back or comes with fever
- Severe constipation, abdominal swelling, or not passing gas or stool
- Chest pain, fainting, or severe weakness after prolonged dehydration
- Sudden vision loss or rapidly worsening eyesight
- Signs of dehydration such as very dark urine, dizziness, confusion
If any of those happen, it is not a “push through it” situation.
That Reddit thread is a reminder of what can go wrong at the extreme end: gallbladder disease after rapid weight loss, pancreatitis, dehydration driven kidney injury, severe constipation with obstruction, aspiration during anaesthesia, and rare eye events.
It is also a reminder that benefits are real, and that rising use means rising absolute numbers of complications even if the percentage risk stays low.