New weight-loss jab yields results similar to bariatric surgery, phase 3 trial finds

Nearly half the participants in an ‘incredibly promising’ phase 3 clinical trial of a new weight-loss jab achieved greater than 30% weight loss – a level long associated with bariatric surgery – according to the drugmaker Eli Lilly.

In the phase 3 TRIUMPH-1 study, 2,339 adults with obesity or who were overweight and had at least one weight-related comorbidity – but without diabetes – were randomised to receive retatrutide in doses of 4mg, 9mg, 12mg, or a placebo.

Participants taking the highest 12mg dose of retatrutide lost an average of 28.3% of their body weight over 80 weeks, while those on the lowest 4mg dose lost an average of 19.0% of their body weight.

Dr Simon Cork, senior lecturer in physiology at Anglia Ruskin University in Cambridge, said: ‘These early results are incredibly promising in showing that we are now truly on the path to combating the obesity crisis.

‘The results demonstrate retatrutide’s superior weight loss effects over all currently available weight-loss medications, with side effects similar to those seen with other GLP-1 based medications.’

The new weight loss injection, retatrutide, is an investigational, once-weekly, triple hormone receptor agonist, which means it activates three key hormone pathways that play a role in glucose metabolism and appetite regulation.

While semaglutide activates GLP-1 receptors, and tirzepatide activates both GIP and GLP-1 receptors, retatrutide also activates a third – glucagon.

Glucagon is a hormone produced by the pancreas that raises blood sugar levels to prevent them from dropping too low. By targeting this pathway, it’s thought that retatrutide may help the body burn more energy as well as eat less.

Dr Ania Jastreboff, lead investigator of the trial, said: ‘It was impressive to see that every dose of retatrutide resulted in clinically meaningful weight reduction for nearly all participants, and people with severe obesity on the highest dose lost on average 30% of their body weight over two years.

‘Importantly, treatment with retatrutide not only resulted in robust weight reduction, but also in clear improvements in assessed cardiometabolic health measures.

‘For patients I see in clinic, retatrutide may potentially be a highly impactful future tool to treat their obesity and transform their health trajectory.’

Eli Lilly also said that of the 532 individuals with a baseline BMI of 35 and over who participated in a study extension, most continued to lose weight after 80 weeks and achieved up to an average of 30.3% weight loss at 104 weeks.

It added that the types of adverse events seen were generally consistent with trials of other similar weight-loss therapies.

The most common adverse events among participants treated with retatrutide were nausea, diarrhoea, constipation, vomiting, and upper respiratory tract infection, with side-effects typically worsening with dose escalation.

Dr Cork said: ‘Dysesthesia – defined as abnormal skin sensations or increased sensitivity to touch – was reported in just over 12% of patients taking the highest dose, which has been reported with other weight loss medications. Notably, most patients who experienced this side effect remained on the medication.’

Eli Lilly also said that discontinuation rates due to adverse events were 4.1%, 6.9% and 11.3%, for retatrutide 4mg, 9mg, and 12mg doses respectively, compared with 4.9% with placebo.

Dr Cork said: ‘Obesity is a life-long, relapsing remitting disease that for many requires active medical treatment in order to control.

‘The rapid advancement of effective and safe drugs for the treatment of obesity should be welcomed, but will take time for health services to adapt to be able to offer these treatments to all who could benefit.’

While this clinical trial did not examine weight regain after stopping retatrutide, other studies have found that discontinuing weight-loss medications like semaglutide and liraglutide typically results in near-total weight regain within about 18 months.

Similarly, as part of the Health and Social Care Committee’s inquiry into food and weight management, MPs recently heard that primary care-led weight management is more effective and cheaper than GLP-1 jabs in the long-term.

While retatrutide is still in the clinical trial phase and Eli Lilly states that it ‘is an investigational molecule that is legally available only to participants in Lilly’s clinical trials,’ promising results from previous trials have led to members of the general public buying knockoff versions online from sellers in China – leading to concerns over patient safety.

A version of this story was first published on our sister title The Pharmacist