Safety and tolerability of new-generation anti-obesity medications: a narrative review

ABSTRACT

The prevalence of obesity and associated comorbidities is rising. Despite their weight-loss efficacy, new generation anti-obesity medications are only prescribed to a minority of adults with obesity, possibly, which in part may be due to safety concerns. This review presents detailed safety profiles for orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion and liraglutide 3.0 mg, and discusses the associated risk–benefit profiles. Two anti-obesity medications presented safety issues that warranted further discussion; phentermine/topiramate (fetal toxicity) and liraglutide 3.0 mg (risk of gallstone disease and mild, acute pancreatitis), whereas the adverse events associated with orlistat, lorcaserin, and naltrexone/bupropion were mostly transient tolerability issues. The difficulties surrounding the objective determination of risk–benefit for anti-obesity medications is discussed. The need for more long-term data, thorough patient assessment, individualization of pharmacological interventions and adherence to stopping rules to maximize risk–benefit are highlighted. Overall, the majority of new generation anti-obesity medications present encouraging tolerability profiles; however, in some cases a lack of long-term clinical trials confounds the accurate determination of risk–benefit.

KEYWORDS:

• Anti-obesity drugs
• liraglutide
• orlistat
• lorcaserin
• phentermine/topiramate
• naltrexone/bupropion

Acknowledgments

The authors are grateful to Jamie Cozens, MSc, and James Currie, PhD, of Watermeadow Medical, Witney, UK (an Ashfield company) for writing assistance in the development of this manuscript. This assistance was funded by Novo Nordisk, which also had a role in the review of the manuscript for scientific accuracy.

Declaration of interest

DKP has participated in speakers bureaux for AstraZeneca, Boehringer Ingelheim, MannKind Corporation, Merck, Novo Nordisk, and Sanofi; and has been a consultant/advisor to Eli Lilly & Co, Regeneron, Sanofi, and The Medicines Company. FCS has been a consultant/advisor to Novo Nordisk. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Author contributions

Dr Patel and Dr Stanford contributed equally to the creation of the manuscript and both approved the final draft.

Additional information

Funding

Support for this paper was funded by Novo Nordisk.