Pharmacist review pending. This page describes clinical trial findings and has not yet been checked by a licensed Canadian pharmacist. Every figure is cited below so you can read the source directly. Do not use it to make a treatment decision.
Quick verdict
Orforglipron side effects are mostly gastrointestinal. They bunch up when someone starts the drug and again at each dose increase, they ease for most people over the following months, and they are the reason roughly one patient in twelve stops taking it. Every figure on this page comes from the approved US label, the FDA's own review of the submission, or the published trial results, and each one says which dose and which trial it belongs to.
One caution before the numbers. A trial reporting rate describes how often something was recorded across thousands of monitored participants. It is not a personal risk estimate, and it cannot tell you what will happen to you. This page is general information, not medical advice. Health Canada has not authorised orforglipron (both Canadian files are still under review), so there is no Canadian product monograph yet, and our Canadian orforglipron tracker is where we log any change to that.
Orforglipron side effects at a glance
Let's break it down into three groups before the detail. The US label for Foundayo, the brand name in the United States, sorts what it found roughly like this:
- Common (5% or more, and above placebo): nausea, constipation, diarrhea, vomiting, indigestion, abdominal pain, headache, bloating, fatigue, burping, acid reflux, gas and hair loss.
- Less common but measured: dizziness, a faster resting heart rate, low blood pressure, low blood sugar, gallstones and changes in taste.
- Rare but serious: pancreatitis, severe stomach reactions, kidney injury from dehydration, gallbladder inflammation, serious allergic reactions, worsening diabetic eye disease, and inhaling stomach contents under anaesthesia.
You can read the full list yourself in the FDA prescribing information for Foundayo. The sections below put numbers on each group.
First, a trap in the dose numbers
The phase 3 trials used capsules dosed at 6, 12 and 36 mg. The product on sale is a tablet, labelled with different numbers for the same drug exposure. FDA confirmed the bridge:
| Trial capsule dose | Marketed tablet strength |
|---|---|
| 6 mg | 5.5 mg |
| 12 mg | 9 mg |
| 36 mg | 17.2 mg |
So a rate reported for the 36 mg arm belongs to the 17.2 mg tablet. Coverage that prints "36 mg" next to a tablet strength has attached the wrong number to the wrong dose. The 14.5 mg tablet was never studied as a target dose in either weight management trial. It exists as a titration step.
Common orforglipron side effects by dose (ATTAIN-1)
ATTAIN-1 is the large trial in adults with obesity or overweight and without type 2 diabetes, published in the New England Journal of Medicine. Denominators are 948 on placebo, 723 on the low dose, 724 on the middle dose and 728 on the highest. Tablet strengths are in the headers.
| Effect | Placebo | 5.5 mg | 9 mg | 17.2 mg |
|---|---|---|---|---|
| Nausea * | 10.4% | 28.9% | 35.9% | 33.7% |
| Constipation * | 9.3% | 21.6% | 29.8% | 25.4% |
| Diarrhea | 9.6% | 21% | 22.8% | 23.1% |
| Vomiting | 3.5% | 13% | 21.4% | 24% |
| Dyspepsia * | 5% | 13.1% | 16.2% | 14.1% |
| Abdominal distension * | 3.4% | 7.2% | 9.4% | 8.5% |
| Decreased appetite * | 3.2% | 5.8% | 8.4% | 7.3% |
| Hair loss | 2.4% | 4.1% | 5% | 5.4% |
* Look at the starred rows. In ATTAIN-1, several effects, nausea and constipation among them, peaked at the 9 mg dose and came down at 17.2 mg. Vomiting climbed steadily. When the label pools ATTAIN-1 with ATTAIN-2, nausea at 9 mg and 17.2 mg lands almost level (34% and 35%) and constipation still tops out at 9 mg (27% against 24%). So the tidy "more drug, more nausea" sentence you see everywhere is too simple. Above the lowest dose, the curve flattens.
Beyond the stomach: headache, fatigue and hair loss
Search results for orforglipron side effects lean hard on nausea. The label lists several other common reactions too, from the pooled weight management trials (1,576 on placebo and just over 1,050 on each dose):
| Reaction | Placebo | 5.5 mg | 9 mg | 17.2 mg |
|---|---|---|---|---|
| Abdominal pain | 7% | 13% | 14% | 14% |
| Headache | 7% | 8% | 9% | 9% |
| Fatigue | 4% | 6% | 7% | 9% |
| Burping (eructation) | 1% | 6% | 8% | 8% |
| Acid reflux (GERD) | 2% | 6% | 6% | 7% |
| Gas (flatulence) | 2% | 5% | 6% | 6% |
| Hair loss | 2% | 4% | 4% | 5% |
Hair loss
Hair loss is one of the most searched orforglipron side effects, so here is exactly what the label says. It links the hair loss seen in the trials to weight reduction. It was far more common in women than in men: 7% of women on the drug against 0.9% of men (3% and 0.7% on placebo). FDA's own analysis found cases started to pull away from placebo at about week 16 and kept rising until about week 48, when they levelled off. That timing fits shedding after rapid weight loss better than a direct drug effect, though the trials were not built to prove the mechanism.
Fatigue, headache and dizziness
Fatigue rose with dose, from 6% to 9% against 4% on placebo. Headache barely moved off the placebo rate. Dizziness was reported by 4% on the drug and 3% on placebo, so most of it would have happened anyway. Our take: if tiredness shows up alongside vomiting or diarrhea, think fluids first. The label's kidney warning (below) is built on exactly that chain.
Heart rate and blood pressure
Like the injectable GLP-1 drugs, orforglipron nudges resting heart rate up. The label reports a mean rise of 4 to 5 beats per minute against 0.5 on placebo, and tachycardia in 3% against 0.9%. Low blood pressure showed up in 2% on the drug against 0.5% on placebo, rising to 4% among people already taking blood pressure medicine.
How long do orforglipron side effects last?
This is the question people ask most, and the FDA review answers it better than any news story. Here is why: reviewers tracked combined nausea, vomiting and diarrhea across ATTAIN-1, ATTAIN-2 and ATTAIN-J over the full 72 weeks.
| Phase | What the trial data show |
|---|---|
| Weeks 1 to 4 | New nausea, vomiting or diarrhea was most likely to start here |
| Weeks 4 to 12 | Prevalence kept rising through the dose climb and peaked around week 12 |
| Week 12 onward | Prevalence declined once people finished escalating to their dose |
| Any single interval | About 14% to 20% of people on the drug had one of the three |
| First 24 weeks | Most stops for side effects happened in this window |
Severity matters as much as timing. Of people on the drug who reported a stomach reaction, the label puts 60% at mild, 36% at moderate and 4% at severe. Severe stomach reactions overall hit about 3% on orforglipron against 1% on placebo. Serious adverse events were no more common on the drug than on placebo, according to the FDA review (6.4% against 6.3%).
The trials also let people pause or step down a dose. Dose adjustments happened in about 21% of people on orforglipron and 9% on placebo, and FDA noted that this flexibility still got over 93% of participants to their target dose. Practical point: a rough first month is common, and it does not predict the next twelve.
How many people stopped
We find this the most useful number on the page, because it measures whether side effects were bad enough to outweigh the benefit rather than simply being present.
| Dose | Discontinued for an adverse reaction |
|---|---|
| 5.5 mg | 6% |
| 9 mg | 9% |
| 17.2 mg | 10% |
| All doses pooled | 8% |
| Placebo | 3% |
Stopped because of an adverse reaction, pooled across the two weight management trials. Gastrointestinal symptoms were the usual reason, and most discontinuations happened during dose escalation in the first 24 weeks rather than later.
Put the other way round: about nine in ten people who started the highest dose stayed on it. That framing matters as much as the side effect table does.
Serious orforglipron side effects and the boxed warning
Foundayo carries a boxed warning for risk of thyroid C-cell tumours, and its wording is unusual enough that a loose paraphrase would misinform you. The label says:
Orforglipron is not pharmacologically active in rats or mice and did not produce tumors in rodents. While orforglipron is pharmacologically active at the human GLP-1 receptor, the human relevance of GLP-1 receptor-dependent thyroid C-cell tumors observed in rodents has not been determined.
Read that carefully. Orforglipron did not cause tumours in rodents. It was non-carcinogenic in a two-year rat study at up to 26 times human exposure. The warning is carried across from the injectable GLP-1 class, where rodent tumours were seen and where the relevance to humans was never settled. The label asks prescribers to tell patients about thyroid tumour symptoms: a lump in the neck, trouble swallowing, shortness of breath or hoarseness that will not go away.
Contraindications
- Personal or family history of medullary thyroid carcinoma, or Multiple Endocrine Neoplasia syndrome type 2
- Known serious hypersensitivity to orforglipron or any of its ingredients
Warnings and precautions, in label order
- Risk of thyroid C-cell tumors
- Acute pancreatitis
- Severe gastrointestinal reactions
- Acute kidney injury due to volume depletion
- Hypoglycemia
- Hypersensitivity reactions
- Diabetic retinopathy complications in patients with type 2 diabetes
- Acute gallbladder disease
- Pulmonary aspiration during general anesthesia or deep sedation
Next steps: what the trials measured for the ones people ask about most.
Pancreatitis
Across the two weight management trials, adjudicators confirmed acute pancreatitis in 6 people on orforglipron (0.14 per 100 years of exposure) against 1 on placebo (0.04). The label tells patients to stop the drug and call their prescriber if they get severe, persistent belly pain, sometimes reaching through to the back, with or without vomiting. Pancreatic enzymes also rose on average (lipase by 26% to 31%), which the label says has unknown meaning without symptoms.
Gallbladder problems
Gallstones were reported in 1% on the drug against 0.7% on placebo, and acute gallbladder inflammation in 0.4% against 0.3%. The label ties these events to weight reduction, a pattern seen across the whole class.
Kidney injury from dehydration
Acute kidney injury was reported in 0.2% on the drug against 0.05% on placebo. Most reported cases across GLP-1 drugs followed vomiting, diarrhea or nausea that led to dehydration. The patient guide is plain about it: drink fluids, and tell your prescriber about nausea, vomiting or diarrhea that does not go away.
Low blood sugar with insulin or sulfonylureas
In ATTAIN-2, which enrolled adults with type 2 diabetes, low glucose (below 54 mg/dL, about 3.0 mmol/L) occurred in 2% on orforglipron against 0.2% on placebo. Combined with a sulfonylurea the rate was 7%, against 0.5% without one. Insulin raises the risk too, and the label suggests prescribers consider lowering those doses at the start. Among people without diabetes in ATTAIN-1, low glucose was recorded in 0.6%.
Allergic reactions, eyes and surgery
Hypersensitivity reactions, anaphylaxis included, occurred in 0.5% against 0.3% on placebo. For people with type 2 diabetes, rapid glucose improvement can briefly worsen diabetic retinopathy, and the drug was not studied in people needing urgent eye treatment. Because it slows stomach emptying, the label also asks patients to tell their care team before any planned surgery or sedation.
Mood and suicidal thoughts
There is no psychiatric or suicidal ideation warning in this label. The FDA review found orforglipron was not associated with a higher risk of depression or suicidal ideation compared with placebo in the phase 3 trials, and depression terms were actually reported less often on the drug.
The liver question
Four drug development programmes in the small-molecule GLP-1 class were discontinued over potential drug-induced liver injury in early trials. That made liver safety the open question going into approval, and regulators looked hard at it.
FDA reviewed liver safety across ATTAIN-1, ATTAIN-2 and ATTAIN-J. Its reviewers concluded there was no strong evidence that orforglipron raises the risk of idiosyncratic liver injury. No case met Hy’s Law with a firm diagnosis, and mean ALT fell on treatment, which tracks weight loss.
FDA still imposed a postmarketing requirement to deliver liver injury data from the ACHIEVE-4 trial, so the question is answered for now rather than closed. Both halves belong in the same paragraph. There is no signal, and the file is not closed. The label does advise against use in severe liver impairment (Child-Pugh C), a dosing caution rather than a sign of injury.
Drug interactions on the label
- Oral birth control pills. The label advises switching to a non-oral method or adding a barrier method for 30 days after starting and for 30 days after each dose increase. The effect on pill absorption has never been tested in a clinical trial. FDA added the advice after disagreeing with Lilly's reading of how slower stomach emptying could affect oral drugs. Patches, rings and other non-oral hormones should not be affected.
- Simvastatin. Orforglipron raised exposure to its active form two to two and a half times, and spacing the doses two hours apart did not prevent it. The label caps simvastatin at 20 mg daily. No relevant change was seen with atorvastatin or rosuvastatin.
- Strong CYP3A4 inhibitors and inducers. Clarithromycin raised orforglipron exposure 3.5-fold and carbamazepine cut it by 82%. The maximum dose drops to 9 mg with a strong inhibitor.
- Other GLP-1 drugs. Taking orforglipron with another GLP-1 receptor agonist is not recommended.
Pregnancy is a separate line in the label rather than an interaction: the drug should be stopped once pregnancy is confirmed, and it is not recommended while breastfeeding.
Orforglipron side effects compared with injectable GLP-1s
You will read that Foundayo is gentler than the injectables. No trial supports that, because no trial has compared orforglipron with Ozempic, Wegovy, Mounjaro or any other injectable GLP-1. One randomised comparison against another GLP-1 exists, ACHIEVE-3, and it ran against oral semaglutide over 52 weeks in 1,698 adults with type 2 diabetes.
| Measure | Orforglipron | Oral semaglutide |
|---|---|---|
| Gastrointestinal adverse events | 58% to 59% | 37% to 45% |
| Discontinued due to adverse events | 9% to 10% | 4% to 5% |
| Mean pulse rate increase | 3.7 to 4.7 bpm | 1.0 to 1.5 bpm |
Orforglipron came off worse on all three, and the trial authors said so. Keep in mind that everyone in it had type 2 diabetes and knew which pill they were taking, and the capsule doses tested were not the tablet strengths sold today. Our full Foundayo and Rybelsus comparison covers that trial in more depth.
FDA's own summary is the fairest one-line answer on class comparison: the safety profile was found to be similar to the approved peptide GLP-1 products, with no new safety signals of concern. Similar. Not gentler. What the pill changes is the delivery (no needles, no fridge, no fasting rule), not the biology behind the nausea. If you want the background on why a pill can do this at all, see how orforglipron works.
Why the titration schedule is long
Because the side effects are front-loaded, the label builds in a slow climb. Each step requires at least 30 days, which puts the maximum dose a minimum of 150 days away, or about five months.
| Step | Dose | Notes |
|---|---|---|
| 1 | 0.8 mg | Starting dose |
| 2 | 2.5 mg | After at least 30 days |
| 3 | 5.5 mg | After at least 30 days. A legitimate maintenance dose. |
| 4 | 9 mg | Optional, after at least 30 days |
| 5 | 14.5 mg | Optional, after at least 30 days |
| 6 | 17.2 mg | Maximum dose |
Two details from the label rarely make it into coverage. The 5.5 mg dose is a legitimate place to stop, not merely a waypoint, and anything above it is optional and based on tolerability. And if seven or more consecutive doses are missed, the label says to restart escalation at a lower dose, which means an interrupted supply can bring the early side effects back.
Reporting a side effect in Canada
Health Canada collects suspected side effect reports through the Canada Vigilance Program, and it says anyone can report. You can file online through the Health Canada side effect reporting form, call toll-free at 1-866-234-2345, or fax 1-866-678-6789. Email is not accepted.
There is a wrinkle with orforglipron. The program is built around products sold in Canada, and this one is not. A Canadian who took tablets dispensed in the United States can still report to Health Canada, and the US label also lists Lilly (1-800-545-5979) and FDA MedWatch (1-800-FDA-1088). Keep the bottle or carton, since the form asks for product details. For anything that feels urgent, such as severe belly pain, signs of an allergic reaction or vomiting you cannot keep fluids down, get medical care first and report later.
What this means for a Canadian reader
You cannot get a Canadian prescription for orforglipron today, so none of the above is a decision you face this week. What it is good for is calibration. If you are weighing whether to wait for this drug or start an authorised one, the honest summary of orforglipron side effects is this: the tolerability looks like the rest of the class rather than better, the worst of it sits in the first three months, and the one direct comparison we have went against it. We would not wait for it on the promise of an easier stomach.
The Health Canada review timeline tracks where the Canadian submissions have reached, and Foundayo in Canada covers what happens before pharmacies can stock it. Any side effect question about a drug you take now belongs with your own doctor or pharmacist.
Common questions
What are the most common orforglipron side effects?
Stomach and bowel effects lead by a wide margin. In ATTAIN-1 at the dose matching the 17.2 mg tablet, nausea was reported by 33.7% of participants, constipation by 25.4%, vomiting by 24.0% and diarrhea by 23.1%, against placebo rates of 10.4%, 9.3%, 3.5% and 9.6%. Headache, tiredness, burping, reflux, gas and hair loss also appear on the US label.
How long do orforglipron side effects last?
For most people in the trials, the stomach effects were a phase rather than a permanent state. FDA reviewers found new nausea, vomiting and diarrhea most likely in the first four weeks, with overall prevalence peaking around week 12 and falling after the dose climb ended. At any given point in the trials, roughly 14% to 20% of people on the drug were dealing with them.
Does orforglipron cause hair loss?
It was reported more often than on placebo: 4% to 5% across doses against 2%, according to the US label. The label links it to weight reduction rather than a direct effect on hair, and it was far more common in women (7%) than men (0.9%). FDA analysis showed cases starting to separate from placebo around week 16 and levelling off near week 48.
How many people stop taking orforglipron because of side effects?
Pooled across both weight management trials, the label reports 8% of participants stopped for an adverse reaction against 3% on placebo, rising from 6% at the 5.5 mg tablet to 10% at 17.2 mg. Stomach symptoms explain most of those exits, and most happened during the dose climb in the first 24 weeks.
Does Foundayo have a boxed warning?
Yes, for risk of thyroid C-cell tumours. The wording is unusual: the label states orforglipron is not pharmacologically active in rats or mice and did not produce tumours in rodents. It carries the warning because the human relevance of GLP-1 related rodent thyroid tumours has not been determined.
Is orforglipron easier on the stomach than Ozempic or Wegovy?
Nobody can say from evidence yet, because no trial has put orforglipron against an injectable GLP-1. The one randomised comparison against another GLP-1, ACHIEVE-3 against oral semaglutide, found more gastrointestinal events and more discontinuations on orforglipron. FDA described its overall safety profile as similar to the approved peptide GLP-1 drugs.
How do I report a side effect in Canada?
Health Canada takes reports through the Canada Vigilance Program, online at canada.ca/medeffect or by phone at 1-866-234-2345, and anyone can file one. Because orforglipron is not sold in Canada, a tablet dispensed in the United States can also be reported to Lilly or to the FDA MedWatch line printed on the US label.
Sources
- FOUNDAYO (orforglipron) tablets, for oral use: Full Prescribing Information. Eli Lilly and Company / U.S. Food and Drug Administration, April 2026.
- NDA Multidisciplinary Review and Evaluation, NDA 220934, FOUNDAYO (orforglipron). U.S. Food and Drug Administration, CDER, April 2026.
- ATTAIN-1 Study Results (NCT05869903). ClinicalTrials.gov, U.S. National Library of Medicine, September 2026.
- Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. New England Journal of Medicine, September 2025.
- Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2). The Lancet, November 2025.
- Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3). The Lancet, February 2026.
- Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and/or Type 2 Diabetes: A Pooled Analysis. Diabetes, Obesity and Metabolism, June 2026.
- Side Effect Reporting Form (Canada Vigilance Program). Health Canada, September 2018.