Novo Nordisk’s experimental weight-loss drug shows mostly mild side effects in trials

Full data from two major Phase 3 trials of Novo Nordisk’s investigational weight-loss treatment, CagriSema, show that most side effects were mild to moderate, with positive outcomes reported for weight reduction and blood sugar control.

CagriSema, a once-weekly injection that combines the GLP-1 receptor agonist semaglutide (used in Wegovy) with cagrilintide, an amylin analogue that suppresses appetite, is being studied as a new treatment option for people living with obesity or type 2 diabetes.

The results, presented at the American Diabetes Association (ADA) Scientific Sessions in Chicago and published in the New England Journal of Medicine, confirm that CagriSema led to substantial weight loss over 68 weeks — almost 23 per cent for people living with obesity and nearly 16 per cent for those living with type 2 diabetes. However, these findings had previously disappointed some investors, contributing to recent leadership changes at the company.

In the obesity trial, 79.6 per cent of participants receiving CagriSema experienced gastrointestinal side effects such as nausea, vomiting or constipation, compared with 39.9 per cent of those on placebo. These effects were mostly mild to moderate and temporary. Serious adverse events occurred in 9.8 per cent of patients on CagriSema, compared with 6.1 per cent in the placebo group. Around 6 per cent discontinued treatment due to side effects, compared with 3.7 per cent in the placebo group.

Dr Melanie Davies, lead investigator for the diabetes trial and co-director of the Leicester Diabetes Centre, said, “Everything was in line with what we expected.” She noted that some patients on lower doses lost more weight than those on higher doses, an unusual pattern suggesting that slower dose escalation may help minimise side effects without compromising results.

Importantly, 73.5 per cent of people treated with CagriSema achieved a glycated haemoglobin (HbA1c) level of 6.5 per cent or less, compared to just 15.9 per cent in the placebo group.

CagriSema’s trial results have been favourably compared to tirzepatide (marketed as Zepbound), currently considered best-in-class. Dr Davies highlighted that having more treatment options is a positive step, particularly as amylin analogues may offer theoretical benefits by boosting energy expenditure — potentially helping counteract the body’s natural resistance to sustained weight loss.

Novo Nordisk expects to file for regulatory approval of CagriSema in early 2026, with possible approval by 2027. Ongoing studies are exploring its effect on cardiovascular outcomes and other long-term health markers.