Anti-obesity injections are less effective in real-world compared to trials, says study

Anti-obesity injections may have smaller effects on weight loss in a real-world context compared to clinical trials, as patients tend to discontinue treatment or use a lower maintenance dose, a study in US patients has found.

Semaglutide, sold under the brand names Wegovy and Ozempic, and tirzepatide (Zepbound and Mounjaro) are prescribed for weight management and treating type 2 diabetes by helping patients regulate blood sugar.

The study, published in the Obesity Journal, examined the effects of anti-obesity injectables on weight reduction and blood sugar regulation (glycaemic control) in a real-world setting.

"Our study shows that patients treated for obesity with semaglutide or tirzepatide lost less weight on average in a regular clinical setting compared to what is observed in randomised clinical trials," lead author Dr Hamlet Gasoyan, a researcher with the Cleveland Clinic, US, said.

"According to our data, this could be explained by higher rates of discontinuation and lower maintenance dosages used in clinical practice, compared to randomised clinical trial settings," Dr Gasoyan said.

The researchers examined 7,881 adult patients with an average body mass index (BMI) of over 39 -- classified as 'severe obesity'. Of these, 1,320 had pre-diabetes at the start of the study, which meant they were at a higher risk of developing type 2 diabetes.

The participants were started on obesity treatments between 2021 and 2023 with semaglutide or tirzepatide injectables.

Following up on the participants a year after starting with the treatment, the average weight loss among those who discontinued injections within three months was 3.6 per cent, compared to 6.8 per cent in those who discontinued within 3-12 months.

"Mean percentage weight reduction at one year was 8.7 per cent, and it was 3.6 per cent with early discontinuation (three months), 6.8 per cent with late discontinuation (3-12 months) and 11.9 per cent with no discontinuation," the authors wrote.

Furthermore, those on a high-maintenance dosage -- the amount required to sustain the effects of the medication -- lost 13.7 per cent of their body weight with semaglutide and 18 per cent with tirzepatide, the researchers said.

Among the participants having pre-diabetes, 33 per cent of those who stopped taking injections within three months experienced normal blood sugar levels, compared to 41 per cent who discontinued within 3-12 months, and 67.9 per cent of those who did not discontinue treatment.

"The average weight reduction in this cohort was lower than that observed in the main phase 3 (clinical) trials, likely because of higher rates of discontinuation and lower maintenance dosages," the team wrote.

They identified that those not discontinuing medications or taking a high-maintenance dose were among the factors related to more chances of losing at least 10 per cent of one's body weight in a year.

Overall, over a fifth of the study group was found to have discontinued their medications within three months of the study's start, while 32 per cent discontinued within 3-12 months.

Reasons for discontinuing treatment included costs and insurance-related issues, side effects and medication shortages, the researchers said.