Obesity medications: A narrative review of current and emerging agents

Abstract

The aim of this narrative review is to synthesize the available data describing the efficacy and safety of medications approved for obesity management and to provide an overview of upcoming agents in development. A literature search of PubMed, Medline, and Embase databases identified relevant articles describing medications approved in the U.S., Australia, U.K., and/or Europe. Papers were selected based on relevance and originality, with phase 3 clinical trials and meta-analyses preferentially included. Six medications are widely approved for long-term weight management in conjunction with lifestyle interventions in people with body mass index (BMI) ≥30 ​kg/m² or BMI ≥27 ​kg/m² and at least one medical condition related to excess weight. Compared with lifestyle interventions alone, all medications approved for obesity management are more effective for long-term weight loss and improvements in cardiometabolic risk factors. Older obesity medications are associated with mean weight losses in the range of 5-10%. The new generation of agents, including the injectable incretin analogues semaglutide and tirzepatide are associated with sustained mean weight reductions of 15-20%, along with substantial benefits on a range of health outcomes. Several novel agents are under development, with multi-hormone receptor agonists and oral formulations likely to become available in the coming years. As effective treatment options expand, cost and availability will need to be addressed to enable equitable access to treatment. Other important challenges for clinical practice and research include the need for long-term strategies to prevent and manage weight regain and loss of lean muscle and bone mineral density.

Keywords: GLP-1; Incretin analogue; Obesity; Pharmacotherapy; Weight loss.

Fig. 1

Heterogeneity in weight loss response after approximately 12 months with currently available agents. Data presented are extracted from the respective phase 3 randomised clinical trials [[25], [26], [27], [28], [29]]. All trials included lifestyle intervention in both drug and placebo arms. Data for naltrexone-bupropion: COR data ad hoc analysis (NB-301). Data on file. iNova Pharmaceuticals (Australia) Pty Limited. Data for phentermine-topiramate are not presented due to the lack of available published data.