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The global rise in the prevalence of obesity has reached epidemic proportions, with the associated comorbidities straining healthcare budgets and adversely affecting the quality and duration of patients’ lives. Any therapy that could bend the curve on this crisis would be welcome. The pharmaceutical class of glucacon-like peptide-1 receptor agonists (GLP-1 RAs) has the potential to be a game changer. These agents, initially developed for glycaemic control, were found to cause significant weight loss in patients with type 2 diabetes. This observation led to trials in patients with obesity but without diabetes, and the resulting weight loss exceeded 8–10 kg at the highest doses evaluated.1 2 Newer agents additionally possessing glucose-dependent insulinotropic polypeptide (GIP) RA activity3 or both GIP and glucagon receptor RA activity4 have produced weight loss up to 20–25% of total body weight, results that rival those from bariatric surgery. The development of orally available GLP-1 RAs5 will likely increase their acceptability and thus market. Public awareness of these drugs is increasing, particularly from extensive television advertisement in the USA. Indeed, the demand has become so great that formulations of GLP-1 RAs approved in the USA for treating diabetes are being used off-label to treat obesity, resulting in shortages for patients needing them for glycaemic control. These agents may also improve cardiovascular function6 and help patients overcome addictions.7 With all this upside, what is not to like?
Well, nausea and vomiting for one. These side effects are reported in up to half of study subjects in clinical trials. While these can be lessened by slower dose escalation or dose reduction, such side effects remain the main reason for patients dropping …
Contributors The listed author is the sole contributor to this work.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.