Open Access
Feature Article

Liraglutide: for obesity, not just type 2 diabetes

Open Access
Feature Article

Liraglutide: for obesity, not just type 2 diabetes

Arianne N Sweeting, Ian D. Caterson

Figures

© PICTURE-FACTORY/ STOCK.ADOBE.COM MODEL USED FOR ILLUSTRATIVE PURPOSES ONLY.
© PICTURE-FACTORY/ STOCK.ADOBE.COM MODEL USED FOR ILLUSTRATIVE PURPOSES ONLY.
Dr Sweeting is an Endocrinologist at Royal Prince Alfred Hospital, Sydney; and a Researcher at the Boden Collaboration of Obesity, Nutrition, Exercise and Eating Disorders, The University of Sydney, Sydney. Professor Caterson is an Endocrinologist at Royal Prince Alfred Hospital, Sydney; and Boden Professor of Human Nutrition at the Boden Collaboration of Obesity, Nutrition, Exercise and Eating Disorders, The University of Sydney, Sydney, NSW.

There is no evidence at present for the efficacy of recommencing the 3 mg liraglutide product for patients who regain weight after treatment cessation. However, it seems reasonable to speculate that reintroducing liraglutide treatment might be of benefit, although there may be a role for alternative interventions, including bariatric surgery.

Adverse effects of liraglutide

Liraglutide is commonly associated with gastrointestinal adverse effects that are generally self-limiting, including nausea, vomiting, diarrhoea or constipation (Box 2). Other frequent adverse effects are hypoglycaemia, particularly in patients with type 2 diabetes, and headache.12 

Uncommon adverse effects of liraglutide include acute pancreatitis and other gastrointestinal effects, such as dyspepsia, abdominal pain, gastro-oesophageal reflux and gastritis. Although an increased incidence of pancreatic cancer was noted in ongoing studies of the GLP-1 receptor agonist class, this does not appear to be an issue in usual clinical management at this stage. Renal impairment due to severe dehydration from nausea and vomiting has also been reported. Liraglutide is also associated with central nervous system effects, including fatigue, dizziness, insomnia, suicidal ideation and depression.16 Allergic and injection site reactions can also occur. 

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Precautions

It is important to note that there are no long-term safety data for the 3 mg liraglutide product. For example, it is associated with an increase in heart rate, but the effects on cardiovascular morbidity and mortality for the 3 mg liraglutide product have not been definitely established, although as discussed above, the results of the LEADER trial appear reassuring.13

Liraglutide is contraindicated in patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, because of an increased incidence of thyroid C-cell tumours observed in rodents.17 It is also contraindicated in those with hypersensitivity or a history of angioedema with other GLP-1 receptor agonists and in pregnancy.

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The 3 mg liraglutide product is not indicated for the treatment of type 2 diabetes and should not be used in combination with other GLP-1 receptor agonists or with insulin. It has not been studied in patients with a history of pancreatitis.

Conclusion

It is well recognised that weight reduction of 5 to 10% from baseline reduces cardiometabolic morbidity and mortality and improves quality of life in patients who are overweight or obese. Although weight loss can be achieved through lifestyle interventions, maintenance of weight loss remains difficult. Liraglutide is the first GLP-1 receptor agonist to be approved as obesity pharmacotherapy and it achieves superior weight loss compared with the only other long-term obesity pharmacotherapy, orlistat. The acceptability, durability of effect and long-term safety of liraglutide for weight loss remain to be seen. Moreover, as liraglutide is not PBS approved, GPs may find the cost prohibitive for their patients.       MT

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COMPETING INTERESTS: Dr Sweeting: None. Professor Caterson has participated in clinical trials of liraglutide, and his institution has received funding for this. He also has received conference registration and accommodation to present the results of these trials at a scientific meeting and has given a talk on obesity for Novo Nordisk.