With the growing incidence of obesity there is a real need for pharmaceutical assistance for losing weight in patients who are unable (or unwilling) to exercise more and eat less
With the growing incidence of obesity, and the resultant impact on population morbidity via the conditions that result, such as Type II diabetes and heart disease, there is a real need for pharmaceutical assistance for losing weight in patients who are unable (or unwilling) to exercise more and eat less. Those that have reached the market thus far have unpleasant gastrointestinal side-effects (orlistat), cause serious cardiac defects (fenfluramine), or an increased risk of heart attack or stroke (sibutramine).
An alternative – and the first to be approved by FDA in more than a decade – has just reached patients. Lorcaserin, marketed by Arena as Belviq, is a serotonergic agent, acting as a selective 5-HT2C receptor agonist.1 By activating these receptors in the hypothalamus, it is thought to cause pro-opiomelanocortin production to kick in, giving a sensation of satiety. This reduction in the desire to eat leads to weight loss.
Numerous trials have been carried out. In one, a randomised, placebo-controlled, double blind, parallel arm trial, a total of 4008 patients with a body mass index above 27 and an obesity-related comorbid condition were given 10mg doses of lorcaserin either once or twice a day, or placebo.2 This was in addition to diet and exercise counselling.
After a year, significantly more patients in the lorcaserin groups had lost at least 5% of their body weight than those in the placebo group – 47% of the twice-daily dosing group, and 40% of the once-a-day group, compared with 25% of those given placebo. Weight loss above 10% of body weight was achieved by 23% and 17% of the two active groups respectively, and 9.7% of those given placebo. The most common drug-related adverse events were headache, nausea and dizziness. The incidence of echocardiographic evidence of heart valve damage was the same – 2% – in both the twice-daily and the placebo groups.
A Phase III trial has also been carried out in patients with Type II diabetes. A total of 604 such patients with a BMI in excess of 27 were enrolled, and again given 10mg doses once or twice a day, or placebo, in addition to diet and exercise advice.3 They were also treated with metformin, a sulfonylurea or both to control their diabetes.
Again, more patients lost more than 5% of their bodyweight on the drug: 38% in the twice-daily group and 45% in the once-a-day group, compared with 16% with placebo. Reductions in the diabetic marker HbA1c in patients given lorcaserin were more than twice as large as those in the placebo group, while the incidence of symptomatic hypoglycaemia was slightly higher in the treated groups. The most common side-effects were headache, nausea, back pain and nasopharyngitis.
Bearing in mind the problems that have occurred with weight loss drugs causing heart valve damage in the past, an analysis of echocardiographic and weight change data from more than 5,000 obese patients in Phase III trials was carried out to assess how many patients developed at least mild aortic or moderate mitral regurgitation.4
After a year on the trials, new valvulopathy was observed in 2.04% of patients given placebo, compared with 2.37% of those given lorcaserin. The researchers concluded that the risk between the two groups was similar, and the slightly higher level for lorcaserin may have been influenced by the greater weight loss in treated patients.
1. B.M. Smith et al. J. Med. Chem. 2008, 51, 305
2. M.C. Fidler et al. J. Clin. Endocrinol. Metab. 2011, 96, 3067
3. P.M. O’Neil et al. Obesity, 2012, 20, 1426
4. N.J. Weissman et al. Circ. Cardiovasc. Imaging, 2013, epub ahead of print