Two other trials in obese and overweight adults without diabetes directly compared liraglutide (at varying doses) with orlistat in conjunction with lifestyle intervention as well as with placebo (i.e. lifestyle intervention alone).10,11 In the earlier of these trials, the mean weight loss with liraglutide was 4.8 kg (for the 1.2 mg dose), 5.5 kg (1.8 mg dose), 6.3 kg (2.4 mg dose) and 7.2 kg (3 mg dose), compared with 4.1 kg for orlistat and 2.8 kg for placebo.10 A follow-up one-year open-label extension study assessed the safety and efficacy of higher-dose liraglutide (initial maintenance dose of 2.4 mg subsequently increased to 3 mg) compared with orlistat. After two years, those taking liraglutide 2.4/3.0 mg sustained a mean weight loss of 7.8 kg from baseline, 3.0 kg greater than the orlistat arm and unchanged from the end of the first year.11
There are no head-to-head studies directly comparing currently available pharmacotherapy. By way of comparison, phentermine, which is an option for short-term (less than three months) weight management therapy in conjunction with lifestyle modification, is associated with weight loss that is about 3.6 kg greater than with placebo (95% confidence interval [CI], 0.6 to 6.0 kg).14 Orlistat, which is approved for long-term weight management and is available without a prescription, is associated with a mean weight loss of 2.89 kg (CI, 2.27 to 3.51 kg) at 12 months.14 Naltrexone hydrochloride/bupropion hydrochloride extended release 8/90 mg combination therapy is the most recent obesity pharmacotherapy approved in Australia. It has a four-week dose escalation schedule, and weight loss of 9 kg compared with 5.2 kg for lifestyle intervention alone has been reported in key studies.15
When is liraglutide used?
The 3 mg liraglutide product is TGA approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults. Criteria for its use are shown in Box 1.
The 3 mg liraglutide product appears more effective than orlistat, which is also TGA approved for chronic weight management. However, longer-term safety and efficacy data are available only for orlistat because it has been available for many years.
How is liraglutide used?
Liraglutide is injected once daily subcutaneously into the abdomen, thigh or upper arm. To minimise the gastrointestinal adverse effects, liraglutide should be started at 0.6 mg daily for one week and increased by 0.6 mg daily at weekly intervals until the maximum 3 mg daily dose is achieved.
GPs should keep in mind the ‘stopping rule’ for the 3 mg liraglutide product for obesity: treatment should be discontinued after 12 weeks on the maximum 3 mg daily dose if the patient has not lost at least 5% of their body weight. Given the lack of long-term safety and efficacy data, therapy continuation should be re-evaluated at this time (i.e. week 16 after treatment initiation) and in an ongoing manner thereafter.
As the 3 mg liraglutide product is approved for chronic weight management, it seems reasonable for patients to continue therapy until they have lost 5 to 10% of their baseline body weight and potentially longer if there is evidence of further and/or durable weight loss associated with treatment. In practice, treatment duration with the 3 mg liraglutide product will ultimately be determined by its cost. Postmarketing studies assessing its longer-term safety will also provide further guidance on treatment duration.