With the global obesity epidemic raging and suggested lifestyle modifications having limited success, the mounting pressures to seek pharmaceutical ‘fixes’ are hardly surprising.
Echoing the principle that everything old is new again, one of the notable weight loss medications is phentermine (Duromine), which has been available for many years. This amphetamine-related drug acts as an appetite suppressant. It has psychoactive effects and is only recommended for short term (up to three months) usage. While the drug does have some efficacy for quick weight loss to increase motivation or to help break through plateaus in a weight loss program, it has been found that weight regain is common once it is ceased. Further, it is contraindicated in patients with cardiovascular disease (CVD) or psychiatric disorder.
Fenfluramine/phentermine (fen-phen) was an anti-obesity drug that utilised two anorectics. But it was later found to cause potentially fatal pulmonary hypertension and heart valve problems, and was withdrawn. Likewise sibutramine was also withdrawn due to cardiovascular events and stroke risk.
Orlistat (Xenical) is a gastric lipase inhibitor which reduces energy intake through the partial elimination of dietary fats. However, if fat intake is above 67gm/day then steatorrhoea develops and this unpleasant side effect has resulted in this drug not having widespread use.
A new drug liraglutide (Saxenda) has come on to the market and was approved by the TGA in Dec 2015 as an adjunctive therapy for obesity. It is a glucagon-like peptide (GLP-1) receptor agonist. It was previously used in type 2 diabetes management at a dose of 1.8 mg daily. For weight loss a higher daily dose of 3 mg is used. It is in the same class as exanatide (Byetta) on the PBS for management of type 2 diabetes.
Saxenda is the first of the GLP-1s to be granted an obesity indication. It is an endogenous incretin, released by intestinal L-cells in response to nutrient ingestion, which enhances glucose-stimulated insulin release by pancreatic beta cells and acts on satiety pathways, including hypothalamic pathways, to reduce food intake.
Peripherally, liraglutide causes appetite to be suppressed and insulin production to be stimulated. Gastric emptying is slowed causing early satiety or a feeling of fullness after a meal. Gastrointestinal adverse effects such as nausea and vomiting also contribute to reduced appetite.
In a recent 56-week randomized placebo-controlled trial involving more than 3,700 adults the 3 mg liraglutide, in conjunction with lifestyle intervention, was associated with an 8.4 kg mean reduction in bodyweight, compared with 2.8 kg for placebo (lifestyle intervention alone).
Using the drug, 63% of subjects lost at least 5% of their initial body weight, while 33% lost at least 10%, compared with 27% and 11% respectively of those receiving placebo. It also achieves superior weight loss to orlistat. Liraglutide was also associated with a significant improvement in cardio-metabolic risk factors, including waist circumference, BSL, blood pressure and sleep apnoea. (1)
Further studies are needed to see whether the 3 mg product may have a role in patients for whom bariatric surgery has failed or is not appropriate.
The 3 mg liraglutide product is TGA approved as an adjunct to lifestyle measures for those with BMI 30 kg/m2 or higher. Also for BMI 27-30 kg/m2 plus at least one weight related co-morbidity (e.g. raised BSLs, hypertension, dyslipidaemia or obstructive sleep apnoea).
As regards side effects, nausea, vomiting, diarrhea, constipation, headache and hypoglycaemia are common. There are no long term safety data for the 3mg liraglutide product. It is associated with an increase in heart rate but the effects on CVD morbidity and mortality have not been established.
It is contraindicated in patients with a personal or family history of medullary thyroid cancer or with hypersensitivity to GLP-1 products. It should not be used in pregnancy or for treatment of type 2 diabetes.
It is not on the PBS and is expensive ($387 per month). It is recommended to use for one year, but to be ceased after three months if there is less than 5% weight loss during that time. GPs can register up to 10 patients into a support program, which will allow them to receive the first month’s medication free, and one session with an accredited nurse educator.
GPs who consider using liraglutide for their eligible patients should study the product information. To assist with prescribing there is a patient support program available to work through the issues for recommending this drug and method of delivery. It is a daily subcutaneous self-injection.
The acceptability, duration of effect and long-term safety of liraglutide remains to be seen, but meantime patients may request this drug, as has happened in my experience, so it is best to be informed.
Astrup A, Rossner S, Van Gaal L et al. Effects of liraglutide in the treatment of obesity: a randomized, double-blind, placebo-controlled study: Lancet 2009; 374:1606-1616
