Good Tidings for Obesity Treatment?Friday, October 23, 2009
Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue with a 97% structural homology to human GLP-1, a gut hormone that plays a key role in the regulation of glucose homeostasis, gut motility and possibly hunger and appetite.
Liraglutide is available in Europe under the brand name Victoza for the treatment of type 2 diabetes, and previous studies have shown that treatment with liraglutide in diabetic patients is also associated with modest, but clinically significant weight loss. (Readers of these pages may recall an earlier posting on similar effects reported for another GLP-1 analogue).
A study by Arne Astrup (University of Copenhagen) and colleagues, published online today in The Lancet, now shows that liraglutide also induces significant weight loss in “non-diabetic” obese patients.
In this double-blind, placebo-controlled 20-week trial, with open-label orlistat comparator, conducted in 19 sites in Europe, 564 individuals (BMI 30–40) were randomly assigned to one of four liraglutide doses (1·2 mg, 1·8 mg, 2·4 mg, or 3·0 mg), to placebo, or to orlistat (120 mg TID). Liraglutide and placebo were administered by once-daily subcutaneous injections.
In addition, all individuals had a 500 kcal per day energy-deficit diet and increased their physical activity throughout the trial, including the 2-week run-in. Weight change analysed by intention to treat was the primary endpoint.
Participants on liraglutide showed a dose-related weight loss ranging from 4·8 to 7.2 kg compared with a 2·8 kg weight loss with placebo and a 4·1 kg weight loss with orlistat.
More individuals lost more than 5% weight with liraglutide 3·0 mg (76%) than with placebo (30%) or orlistat (44%).
Liraglutide also reduced blood pressure at all doses and reduced the prevalence of prediabetes by around 90%.
The main adverse effects of liraglutide were nausea and vomiting, occurring in upto one-third of patients at the highest dose, but adverse events were mainly transient and rarely led to discontinuation of treatment.
The authors conclude that liraglutide treatment over 20 weeks is well tolerated, induces clinically meaningful weight loss, and improves certain obesity related risk factors in non-diabetic obese patients.
While the degree of weight loss is not substantially different from that seen with current anti-obesity drugs, the results of this study are certainly exciting because they possibly open a whole new avenue of anti-obesity treatments targeting gut hormones (incretins).
Although liraglutide has to be delivered by once-daily injections (its circulating half-life is 13 h), I am confident that there will be enough people struggling with excess weight only too happy to jump at the option.
Obviously, longer-term studies will be required to demonstrate both the long-term safety and efficacy of GLP-1 analogues in the treatment of obesity both in diabetic and non-diabetic patients but these early results certainly appear promising.
Disclaimer: I have received speaking and consulting honoraria from Novo-Nordisk, the maker of liraglutide.