liraglutide and weight management

Few safe and effective drugs are currently available for the treatment of obesity. This interesting paper looks at the use of liraglutide, a drug used in diabetic control on weight reduction. The aim of the study was to assess the effect on bodyweight of liraglutide (at doses up to 3·0 mg per day), in combination with an energy-deficit low-fat diet and physical activity
Liraglutide is a glucagon-like peptide-l (GLP-1) analogue with a 97% structural homology to human GLP-1, a gut-derived incretin hormone. Liraglutide has a long half-life of about 13 h and is given once a day by subcutaneous injection. Liraglutide is used for the treatment of type 2 diabetes mellitus and has benefits for glycaemic control at doses up to 1· 8 mg a day.
Because liraglutide also causes a dose-dependent weight loss, and benefits to the concentration of glycosylated haemoglobin (HbA,,) and systolic blood pressure, and has the potential as an attractive treatment option for both type 2 diabetes and obesity.
The underlying mechanisms for the effects on weight reduction of liraglutide are probably through effects on the gastrointestinal tract and the brain. Native GLP-l suppresses appetite and energy intake in both normal-weight and obese individuals, as well as in people with type 2 diabetes, and delays gastric emptying.
GLP-l receptors are expressed in several brainstem nuclei involved in appetite regulation, and subcutaneously administered liraglutide might also reach these sites.

The study was a double-blind, placebo-controlled 20-week trial, with 564 individuals (18-65 years of age, body-mass index 30-40 kg/ml) who were randomly assigned, to one of four liraglutide doses (1·2 mg, 1·8 mg, 2·4 mg, or 3-0 mg, n=90-95) or to placebo (n=98) administered once a day subcutaneously, or orlistat (120 mg, n=95) three times a day orally. Orlistat blocks intestinal lipase activity. 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.
Mean weight loss with liraglutide 1·2-3·0 mg was 4·8 kg, 5·5 kg, 6·3 kg, and 7·2 kg compared with 2·8 kg with placebo and 4·1 kg with orlistat, and was 2·1 kg to 4·4 kg (2·9-6·0) greater than that with placebo.
Liraglutide reduced blood pressure at all doses, and reduced the prevalence of prediabetes (84–96% reduction).
Nausea and vomiting occurred more often in individuals on liraglutide than in those on placebo, but adverse events were mainly transient and rarely led to discontinuation of treatment.
Liraglutide treatment over 20 weeks is well tolerated, induces weight loss, improves certain obesity-related risk factors, and reduces prediabetes.
Astrup, et al (2009 ) Effects of liraglutide in the treatment of obesity:
a randomised, double-blind, placebo-controlled study . The Lancet vol 374 pp1606-16
Bray 2009 Gastrointestinal hormones and weight management . Lancet vol 374 pp 1570-1

Martin Eastwood
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