Quick answer: the main cagrilintide side effects in clinical trials were nausea, constipation, diarrhea and injection-site reactions. Taken alone in a phase 2 trial, cagrilintide caused stomach side effects in 41% to 63% of people depending on dose, versus 32% on placebo, mostly nausea (20% to 47% versus 18%).[1] Combined with semaglutide as CagriSema, 79.6% had stomach side effects versus 39.9% on placebo, mostly mild to moderate and temporary.[2]
Cagrilintide is an investigational amylin analog from Novo Nordisk and is not FDA-approved. For background, see the cagrilintide profile and our CagriSema guide.
Why cagrilintide causes nausea
Amylin, the hormone cagrilintide mimics, slows how fast the stomach empties and signals fullness to the brain.[12] Those are the same actions that reduce appetite, and slower stomach emptying is a common source of nausea, fullness and constipation. As with GLP-1 drugs, the effects tend to be strongest while the dose is being raised.
Side effects of cagrilintide alone
Phase 2 dose-finding trial
In 706 adults treated for 26 weeks with 0.3 to 4.5 mg weekly:[1]
- Most frequent side effects: gastrointestinal problems (nausea, constipation, diarrhea) and administration-site reactions.
- Stomach side effects: 41% to 63% on cagrilintide versus 32% on placebo, rising with dose.
- Nausea: 20% to 47% versus 18%.
- Stopping treatment: 10% of all participants stopped permanently, at similar rates across groups, most often because of side effects (4% overall).
Phase 3 trials
- REDEFINE 1: Novo Nordisk said cagrilintide 2.4 mg alone appeared safe and well tolerated. At week 68, 82.5% of people on it were on the top dose, compared with 70.2% on semaglutide 2.4 mg and 57.3% on CagriSema.[4]
- REIMAGINE 2: in people with type 2 diabetes, any adverse event was reported by 82.2% on cagrilintide 2.4 mg, 81.2% on semaglutide 2.4 mg, 86.9% on CagriSema and 70.5% on placebo over 68 weeks. Stomach problems were the most common in every active group.[5]
- Phase 2 in type 2 diabetes: adverse events were reported by 80% on cagrilintide, 71% on semaglutide and 68% on CagriSema, mostly mild or moderate stomach effects. No moderate or severe low blood sugar and no deaths were reported.[6]
| Trial | Group | Any adverse event | Comparison |
|---|---|---|---|
| REIMAGINE 2 (68 weeks) | Cagrilintide 2.4 mg | 82.2% | Placebo 70.5% |
| Phase 2, type 2 diabetes (32 weeks) | Cagrilintide 2.4 mg | 80% | Semaglutide 71% |
| Phase 2, obesity (26 weeks) | Cagrilintide 0.3 to 4.5 mg | Stomach effects 41% to 63% | Placebo 32% |
Sources: REIMAGINE 2,[5] phase 2 diabetes[6] and phase 2 obesity.[1]
Side effects of CagriSema (cagrilintide plus semaglutide)
Most people who will ever take cagrilintide are likely to take it as CagriSema, so these data matter most.
- Phase 1b (95 adults, 20 weeks): with semaglutide 2.4 mg as the base, 69 of 71 people on added cagrilintide and 23 of 24 on added placebo reported at least one adverse event. About 37% of all events were gastrointestinal, and most were mild to moderate.[7]
- REDEFINE 1 (3,417 adults, 68 weeks): gastrointestinal side effects including nausea, vomiting, diarrhea, constipation or stomach pain affected 79.6% versus 39.9% on placebo. They were mainly transient and mild to moderate.[2]
- REDEFINE 2 (1,206 adults with type 2 diabetes): 72.5% versus 34.4%.[3]
- REDEFINE 5 (331 adults in Japan and Taiwan): stomach side effects were similar to semaglutide alone, 53% versus 51%.[8]
- REIMAGINE 1 (early type 2 diabetes, 40 weeks): adverse events in 79% on 2.4/2.4 mg, 75% on 1.0/1.0 mg and 66% on placebo, mostly mild or moderate and stomach-related.[15]
Dose reductions
REDEFINE 1 let people stay on a lower dose if needed. Only 57.3% of the CagriSema group were on the full 2.4/2.4 mg dose at week 68.[4]
For practical tips that apply across this drug class, see GLP-1 nausea, GLP-1 constipation and GLP-1 side effects.
Low blood sugar
In people with type 2 diabetes, severe low blood sugar was not a feature:
- No moderate or severe (level 2 or 3) hypoglycemia occurred in the phase 2 diabetes trial.[6]
- In REIMAGINE 3, where CagriSema was added to basal insulin, no severe hypoglycemia was reported.[9]
Semaglutide’s label warns that combining a GLP-1 drug with insulin or a sulfonylurea can raise the risk of low blood sugar, so those doses may need lowering.[13]
Heart, kidney and liver
- Heart rhythm: in a dedicated QT study, 53 healthy volunteers escalated to 4.5 mg showed no clinically relevant prolongation of the QT interval, a measure linked to dangerous heart rhythms.[10]
- Kidney and liver impairment: in single-dose studies, no serious adverse events occurred, and side effects did not increase with worse kidney or liver function.[11]
- Heart outcomes: not yet known for CagriSema; the REDEFINE 3 outcomes trial is ongoing. See CagriSema vs Zepbound.
Warnings that come with semaglutide
CagriSema’s final label is not yet known. Its semaglutide component already carries warnings on the Wegovy label, including a boxed warning about thyroid C-cell tumors in rodents, plus acute pancreatitis and gallbladder disease.[13] It is reasonable to expect a CagriSema label to include at least these, but only FDA can confirm that.
The Wegovy label also says semaglutide should not be combined with other GLP-1 receptor agonists.[13] That is one reason combining cagrilintide products with other weight-loss injections is a concern; see cagrilintide with retatrutide.
Products sold outside trials
FDA says cagrilintide cannot be used in compounding under federal law and has not been found safe and effective for any condition.[14] Side effects from products sold online may not match the trial data at all, because their content and dose are unverified.
Questions to ask a clinician
- What side effects should I expect while the dose is increased, and how do we manage them?
- Do I take insulin or a sulfonylurea that would need adjusting?
- Do I have a history of pancreatitis, gallbladder disease or thyroid cancer in the family?
- Would an approved option suit me while CagriSema is under review?
For trial doses and titration, see cagrilintide dosage, and for the wider field, the GLP-1 drugs hub.
