Endocrine Abstracts

Obesity is a chronic relapsing disease with significant adverse implications for current and future health. Whilst guidelines recommend first line treatment with lifestyle interventions that include restriction of energy intake, increased physical activity and behavioural modification, these only demonstrate an average decrease of 3–5% initial body weight over 12 months, and weight regain is common. Bariatric surgery is effective, but is generally only offered to people with more severe obesity (usually defined as a BMI > 40-kg/m², or > 35 kg/m² if significant complications are present; it may be offered to those with a BMI >30 kg/m² in those with recent onset type 2 diabetes). Surgery may result in significant complications and is not suitable for everyone. Pharmacotherapy should be considered an adjunct to lifestyle intervention and may help bridge the efficacy gap between lifestyle and surgery. Current anti-obesity agents available in the USA (not all are approved in Europe or other countries) include the peripherally-acting intestinal lipase inhibitor, orlistat, and the centrally acting drugs, which work to modulate various aspects of appetite regulation. These include the 5HT_2c receptor agonist lorcaserin, a combination of the mu opioid antagonist naltrexone with bupropion, phentermine as monotherapy, or in combination with topiramate, and liraglutide, a GLP-1 receptor analogue that is also approved at lower doses for use as glucose lowering agent in type 2 diabetes. These agents provide approximately 3–6% greater weight loss than lifestyle intervention alone over 12 months or more treatment duration. Adverse effects depend on the mode of action, and regulators have focussed on cardiac and neuropsychiatric safety given previous problems with older (now withdrawn) medicines for weight loss such as sibutramine and rimonabant. Lorcaserin was recently shown to be safe from a cardiovascular perspective, and data with the lower dose of liraglutide in people with diabetes suggests cardioprotection in those at high risk. The recently reported results of a phase 2 trial with the GLP1 agonist semaglutide are promising and suggest even greater weight loss is possible with some approaches. Future developments will likely target multiple pathways in an attempt to optimise efficacy and approach the weight loss seen with surgical approaches.