Liraglutide is TGA approved as an adjunctive therapy for obesity, extending its indications for use beyond treatment of type 2 diabetes. What is its place in helping patients achieve and maintain weight loss?
The chronic nature of obesity has led to renewed interest in pharmacotherapy as an adjunct to lifestyle intervention for achieving and maintaining weight loss. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that was previously TGA approved for the treatment of type 2 diabetes, at a dose of 1.8 mg daily. In December 2015, the TGA approved a liraglutide product with a higher daily dose (3 mg) for the treatment of obesity. The 3 mg product has potential as a long-term obesity therapy, although current long-term safety and efficacy data are limited.
The weight loss effects of the 3 mg liraglutide product appear superior to those of orlistat, the only other approved long-term obesity pharmacotherapy. The 3 mg liraglutide product can be prescribed by GPs, although the cost of a private prescription ($387 per month) may prove prohibitive for many patients.
What is liraglutide?
Liraglutide is an analogue of human GLP-1, a hormone that suppresses appetite and stimulates insulin secretion. Weight loss with liraglutide appears to be due to reduced appetite and energy intake.1 Peripherally, GLP-1 receptor agonists slow gastric emptying, causing early satiety. Gastrointestinal adverse effects associated with these agents, such as nausea and vomiting, likely also contribute to reduced appetite.2,3
Weight loss associated with GLP-1 receptor agonists can, however, occur in the absence of nausea and vomiting and independent of delayed gastric emptying.4 Recent studies suggest that the weight loss effects of liraglutide may therefore be predominantly mediated through its action within the central nervous system, as liraglutide is able to cross the blood–brain barrier.5,6 This central induction of satiety may explain the greater weight loss effects seen with liraglutide compared with other larger nonpeptide GLP-1 receptor agonists.
How does liraglutide compare with other agents?
Trials of the lower-dose liraglutide product in the treatment of patients for type 2 diabetes consistently found it to be associated with modest weight reduction.7,8 This finding led to three trials in adults with obesity or overweight without diabetes, which confirmed a dose-dependent weight reduction with liraglutide.9-11
In a 56-week randomised placebo-controlled trial involving more than 3700 adults, the 3 mg liraglutide product in conjunction with lifestyle intervention was associated with a mean 8.4 kg reduction in body weight, compared with 2.8 kg for placebo (lifestyle intervention alone) – i.e. a 5.6 kg mean-subtracted weight loss with liraglutide.12 Among participants receiving liraglutide, 63% lost at least 5% of their initial body weight, and 33% lost at least 10%, compared with 27% and 11%, respectively, of those receiving placebo. Liraglutide was also associated with a significant improvement in cardiometabolic risk factors, including reductions in waist circumference, blood glucose level, blood pressure and sleep apnoea.12 The cardiovascular benefits of liraglutide were confirmed by the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial which reported lower cardiovascular mortality and morbidity (nonfatal myocardial infarction or stroke) in patients with type 2 diabetes treated with liraglutide 1.8 mg compared with placebo over a median follow up of 3.8 years.13