Cagrilintide side effects: how often each one happened in the trials

Two things stand out. Cagrilintide alone produces fewer stomach effects than the combination, but more than placebo, and the gap rises with dose. And the combination's stomach effects in phase 3 run at roughly twice the placebo rate, which is the usual pattern for drugs in this group.

Nausea is the signature side effect. In phase 2 its rate climbed with the dose, from 20% at the lowest cagrilintide dose to 47% at the highest, against 18% on placebo ^[1]. Constipation and diarrhoea were the other common gastrointestinal events in that trial ^[1]. In REDEFINE 1, nausea affected 55% on CagriSema against 12.6% on placebo, constipation 30.7% against 11.6%, and vomiting 26.1% against 4.1% ^[5].

The reason is mechanistic. Amylin slows gastric emptying and acts on brainstem areas that control appetite ^[8], and cagrilintide works partly through the area postrema ^[9], the brainstem region that also triggers nausea. That is one reason Eli Lilly built eloralintide to be more selective: in rats it produced less conditioned taste avoidance than cagrilintide ^[10]. The broader comparison of these drugs is in amylin analogs.

The phase 2 monotherapy trial listed administration-site reactions alongside gastrointestinal disorders as the most frequent adverse events with cagrilintide ^[1]. The published abstract does not give a rate for them, and the phase 3 publications summarised here do not report injection-site rates for cagrilintide alone. So the evidence supports saying these reactions were common in phase 2, not putting a number on them. Figures quoted elsewhere without a trial name should be treated with caution. Injection technique and site rotation are covered in subcutaneous injection sites.

In that trial, in adults with type 2 diabetes, cagrilintide alone and semaglutide alone produced almost the same overall rate of adverse events, and gastrointestinal disorders were the most common in every active group ^[3]. In the smaller phase 2 diabetes trial the figures were 80% on cagrilintide, 71% on semaglutide and 68% on CagriSema ^[4], numbers too small to rank them.

Adding cagrilintide to semaglutide raises the rate modestly. In REDEFINE 5, gastrointestinal events affected 53% on CagriSema against 51% on semaglutide alone, while 10% stopped CagriSema against 6% who stopped semaglutide ^[7]. Pooled analyses put this in context: one 2026 meta-analysis found adverse events more frequent with cagrilintide or CagriSema than placebo but discontinuation rates comparable to placebo ^[11], and a network meta-analysis found that only high-dose CagriSema increased discontinuation for adverse events ^[12]. The head-to-head arms are compared in full in cagrilintide vs semaglutide.

The trials describe gastrointestinal effects as mainly transient and mild to moderate ^[2][6]. They cluster during the period when the amount is being raised, which is why every trial escalated gradually: the phase 2 trial used a dose-escalation period of up to 6 weeks ^[1], and the phase 1b trial co-escalated cagrilintide and semaglutide in 4-week steps over 16 weeks ^[13]. Those schedules are reported here as what the trials administered, not as a plan for anyone; they are tabulated in cagrilintide dosage.

Because cagrilintide has a half-life of 159 to 195 hours ^[13], an effect that starts after an injection can take days to fade. The published abstracts do not give a week-by-week curve of side effects for cagrilintide alone.

• Heart rhythm. A thorough QT study in 105 healthy adults, with 53 escalated to 4.5 mg of cagrilintide, found no clinically relevant QTc prolongation ^[14].
• Kidney and liver. In dedicated studies, kidney or liver impairment produced no increase in adverse events and no new safety findings ^[15].
• Low blood sugar. In the phase 2 trial in type 2 diabetes, no level 2 or level 3 hypoglycaemia and no fatal adverse events were reported ^[4].
• Deaths. REDEFINE 5 reported one death, in the semaglutide group, judged unrelated to treatment ^[7].
• Class pattern. REIMAGINE 2 described the CagriSema safety profile as consistent with the GLP-1 receptor agonist class and previous cagrilintide data ^[3].

• Long-term use. The longest completed trials ran 68 weeks for weight loss ^[2]. The CagriSema cardiovascular-outcomes trial, REDEFINE 3, is still running ^[5].
• Cagrilintide alone in phase 3. The dedicated RENEW trials have started but not reported ^[16].
• Rare events. Trials of a few thousand people can miss uncommon harms; no regulator has yet reviewed the full safety file and published a label ^[5].
• Products outside trials. Every number on this page describes the manufacturer's drug in monitored trials. For anything sold under the name, identity, purity and dose are unknown, which adds risks no trial measured.