Navigating the benefits and harms of GLP-1 and GLP-1/GIP agonists in obesity

Obesity is becoming increasingly common worldwide. Glucagon-like peptide-1 receptor agonist (GLP-1 RA) type drugs have the potential to help patients achieve considerable weight loss. Several benefits have been described in the short term, especially relating to diseases associated with obesity, where rapid weight loss results in undoubted improvements. These conditions include type 2 diabetes mellitus, cardiovascular disease and metabolic dysfunction-associated steatotic liver disease. Known adverse effects include gastrointestinal (nausea, vomiting, acute pancreatitis, dehydration and malnutrition), reduced efficacy of oral contraceptives and allergic reactions. Rarer adverse effects include thyroid cell tumours and non-arteritic anterior ischaemic optic neuropathy. Up to 33% of the weight lost is lean tissue mass (muscle and bone). Discontinuation rates can be up to 80% after 2 years. Subsequent weight regain can be up to two-thirds of prior weight loss. There is a risk of much of this regain being fatty tissue. To avoid this and associated malnutrition, GLP-1 RAs should only be initiated along with a supervised exercise programme and individualised dietetic advice. Subsequent patient monitoring to detect cessation, malnutrition and inappropriate fatty tissue weight gain is recommended.