Early Response to Liraglutide Predicts Long-term Weight Loss

Those who lose weight early with liraglutide 3.0 mg are more likely to achieve long-term weight loss, according to a post-hoc analysis of the SCALE Obesity and Prediabetes and Diabetes trials.  

In addition, patients who have not achieved at least a 5% body weight loss by week 16 of treatment with liraglutide 3.0 mg are unlikely to achieve a greater than 10% weight loss after 1 year of treatment, researchers reported at the International Diabetes Federation’s World Diabetes Congress in Vancouver, Canada.

Identification of patients who respond best to anti-obesity medications is important to limit use in those who do not respond to the treatment, thereby improving the cost effectiveness of these drugs. This is a huge concern among clinicians as well as third party payers, noted John Wilding, DM, who is a professor of medicine and honorary consultant physician at the University of Liverpool in the United Kingdom.

“I think the key findings here are that people who have an early response to liraglutide 3.0 mg, such as a 5% weight loss at 16 weeks after starting the medicine, are very likely to maintain that weight loss after 1 year (more than 80%) and have a very good chance of achieving a 10% weight loss and nearly a quarter will achieve a 15% weight loss,” he said. “This allows physicians to tell patients that they can have a trial of treatment and if the response is good, they are likely to continue to do well.”

He noted that there are now so-called “stopping rules” in the labels of anti-obesity medications, the researchers noted. In Canada and in the European Union, prescribing information states that liraglutide 3.0 mg should be discontinued after 12 weeks on the 3.0 mg per day dose if a patient has not lost at least 5% of their initial body weight, with the label stating that it is unlikely that the person will achieve and sustain clinically meaningful weight loss with continued treatment.

Liraglutide 3.0 mg is a once-daily injectable glucagon-like-peptide 1 (GLP-1) receptor agonist with 97% similarity to naturally occurring human GLP-1. It regulates appetite by reducing hunger and increasing fullness, making people feel satisfied and eat less food. Currently, liraglutide 3.0 mg is an approved treatment for weight management in the European Union, United States, Canada, and Mexico.

“Similar analyses have been done for other weight-loss drugs and the requirement for identification of early responders/nonresponders is part of the label for liraglutide in the U.S. and Europe. It makes sense to stop the drug as soon as possible in people who don’t respond well enough to achieve clinical benefit, but we can also see that the responders do better than the average seen in the clinical trials,” Dr Wilding told Endocrinology Advisor.

In this current analysis, patients with obesity achieving at least 5% weight loss at week 16 on liraglutide 3.0 mg were categorized as early responders to liraglutide 3.0 mg. They were compared with those who did not achieve a 5% weight loss who were labeled as early nonresponders to liraglutide 3.0 mg. 

A weight loss of at least 5% at week 16 offered the best prediction of achieving 10% weight loss at week 56.

A total of 2910 adults were randomly assigned to liraglutide 3.0 mg as an adjunct to diet and exercise. In this cohort, there were 2487 patients without type 2 diabetes and a BMI of at least 30 or 27 to 29.9 with at least 1 obesity-related comorbidity. Mean age was 45 years, and 21% were men.

Among the 423 patients with type 2 diabetes, the patients had a BMI of at least 27. Mean age was 55 years, and 52% were men.

Dr Wilding said 2152 patients without type 2 diabetes and 365 with type 2 diabetes completed 16 weeks of the trial.

The study demonstrated that 68% of week 16 completers without type 2 diabetes were early responders to liraglutide, with a mean weight loss of 11.5% at week 56.

At week 56, 88% of early responders achieved at least 5% weight loss, 55% achieved at least 10% weight loss, and 24% achieved more than 15% weight loss, according to the data.

Early nonresponders without type 2 diabetes achieved a mean weight loss of 3.8% at 56 weeks.

Greater improvements in cardiovascular risk factors were also seen in early responders compared with the early nonresponders.

Overall, safety was generally comparable between early responders and early nonresponders. Rates of hepatobiliary disorders in those without type 2 diabetes appeared higher in early responders than early nonresponders (3.5% vs 2.1%).

Disclosure: This trial was funded by Novo Nordisk. Novo Nordisk was an active contributor to all parts of this abstract, including statistical analyses.

Reference

1. Blüher M, Hermansen K, Greenway F, et al. Early weight loss with liraglutide 3.0 mg is a good predictor of clinically meaningful weight loss after 56 weeks. Presented at the World Diabetes Congress; November 30-December 4, 2015; Vancouver, Canada.