A narrative review of anti-obesity medications for obese patients with osteoarthritis

ABSTRACT

Introduction

The prevalence of both obesity and osteoarthritis (OA) is increasing worldwide (twindemic), and the association between the two chronic diseases is also well established.

Areas covered

In this narrative review, we will briefly describe the double burdens of both diseases, the impact of weight loss or gain on OA incidence and structural progression and discuss the biomechanical and anti-inflammatory mechanisms mediating these effects. FDA-approved anti-obesity drugs are summarized in terms of their clinical efficacy and safety profile, and the completed or ongoing phase 2/3 clinical trials of such drugs in OA patients with obesity are examined.

Expert opinion

We will discuss the perspectives related to principles of prescription of anti-obesity drugs, the potential role of phenotype-guided approach, time to drug effects in clinical trials, sustainability of weight loss based on the real-world studies, the importance of concomitant therapies, such as dieting and exercises, and the role of weight loss on non-weight bearing OA joints. Although obesity is the major risk factor for OA pathogenesis and progression, and there are a variety of anti-obesity medications on the market, research on the use of these disease-modifying drugs in OA (DMOAD) is still sparse.

KEYWORDS:

• Osteoarthritis
• obesity
• anti-obesity drugs
• disease-modifying
• DMOAD
• diet
• exercise

Article highlights

• Labelling obesity as ‘modifiable’ risk factor for OA is too simplistic as obesity itself is a chronic, relapsing disease with sustained long-term weight loss being extremely challenging.

• Every 5-unit increase in BMI can lead to a 35% increased risk of knee OA while weight loss of 5.1 kg over the 10 years decreased the odds for developing knee OA by 54%.

• Anti-obesity medications are indicated if BMI is 30 or higher, or if it is at least 27 with one obesity-related comorbidity if lifestyle interventions fail

• Among the pharmacological treatment, orlistat produces the lowest weight loss while Semaglutide results in the greatest weight loss

• Anti-obesity medications are still underused with only 2.4% being prescribed with anti-obesity pharmacotherapy in 2019

• Despite the enormous disease burden and established pathogenic link, clinical trials of weight-loss medications in OA are still sparse.

Acknowledgments

DJ Hunter is supported by an NHMRC Investigator Grant. A Mobasheri is supported by the Academy of Finland Profi6 336449 grant awarded to the University of Oulu, the European Commission and the European Structural and Social Funds (ES Struktūrinės Paramos) awarded through the Research Council of Lithuania (Lietuvos Mokslo Taryba) and the funding programme: Attracting Foreign Researchers for Research Implementation (2018-2022), Grant No 01.2.2-LMT-K-718-02-0022.

Author contributions

WMO, DJH and AM contributed to the study concept and design.

WMO conducted the data search, constructed the illustrations, and drafted the first version of the manuscript.

DJH, AM and WMO critically revised the manuscript for important intellectual content.

Declaration of interest

DJ Hunter provides consulting advice on scientific advisory boards for Pfizer, Lilly, TLCBio, Novartis, Kolon TissueGene, Biobone. A Mobasheri consults for GSK Consumer Healthcare, Kolon TissueGene, Laboratoires Expansciences, Novartis, Orion Corporation and Sanofi. He is President of the Osteoarthritis Research Society International (OARSI) (May 2019 – April 2022) and serves on the Scientific Advisory Boards of Kolon TissueGene, ResearchSquare and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). 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.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.