This study was needed because some patients have limited tolerance to incretin receptor agonists such as semaglutide (Ozempic, Wigovy, and Rebelsus), or they do not achieve their weight loss goals using them.
Previous studies have shown that the hormone amylin helps regulate satiety and weight, and drugs that stimulate its receptors and calcitonin receptors have been tested to reduce appetite. Eluralintide belongs to this class of drugs, targeting the same biological pathway to provide an effective and well-tolerated weight-loss option.
The study included 263 participants at 46 centers in the United States, ranging in age from 18 to 75 years, with a mean age of 49 years and a mean body mass index of 39.1 kg/m² (classified as Class II obesity, meaning high obesity close to morbid obesity). Participants were randomly assigned to receive either a placebo or eluralintide at different doses (1, 3, 6, and 9 mg, or dose-increasing plans of 3-9 and 6-9 mg) for 48 weeks, followed by a 10-week follow-up.
Participants received weekly subcutaneous injections, and the treatment was accompanied by lifestyle and dietary counseling. Statistical models were used to estimate the drug's effectiveness, focusing on the percentage change in weight as the primary endpoint, along with secondary indicators such as body mass index, waist circumference, blood glucose and lipid levels, and high-sensitivity C-reactive protein.
All eloralintide groups showed a significant weight loss compared to placebo (only -0.4% of baseline weight). The percentages of weight loss were recorded as follows:
1 mg: -9%.
3 mg: -12%.
6 mg: -18%.
9 mg: -20%.
6-9 mg: -20%.
3-9 mg: -16%.
Participants who took the higher doses also experienced a reduction in waist circumference of up to 17.1 cm, and a body mass index of up to 7.8 kg/m², and a greater number of them achieved weight loss of at least 5%, 10%, 15% and 20%, with some groups reaching a loss of 25-30%.
Side effects occurred in 81% of participants taking eluralintide and 71% of those receiving placebo. Nausea and fatigue were the most common side effects. Tolerability was better when the dose was increased gradually rather than starting with high doses. No cases of pancreatitis or cholecystitis were reported, and there were no deaths. However, 10% of participants had to discontinue treatment due to side effects.
The study demonstrated that eloralintide achieves clinically significant dose-related weight loss with acceptable tolerability, highlighting its potential role as a weight management option for non-diabetic adults.
The results indicate the need for future studies to evaluate its effectiveness across different population groups and in complex treatment regimens.
The study was published in the journal "The Lancet".
