Metabolically unhealthy obesity, sarcopenia and their interactions in obesity pathophysiology and therapeutics: Room for improvement in pharmacotherapy

Obesity is the fastest-growing medical condition, globally, with the current prevalence being approximately 30 %. This metabolic disorder is magnified by the prevalence of overweight being observed in a further 30 % of the population. Such numbers stand in stark contrast to what characterized the population several decades ago [ 1 Kivimäki M. Kuosma E. Ferrie J.E. Luukkonen R. Nyberg S.T. Alfredsson L. et al. Overweight, obesity, and risk of cardiometabolic multimorbidity: pooled analysis of individual-level data for 120813 adults from 16 cohort studies from the USA and Europe. Lancet Public Health. 2017; 2: e277-e285https://doi.org/10.1016/S2468-2667(17)30074-9 Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar ]. In the United States (US), obesity affects around 40 % of adults [ 2 Angrisani L. Santonicola A. Iovino P. Vitiello A. Higa K. Himpens J. et al. IFSO worldwide survey 2016: primary, endoluminal, and revisional procedures. Obes Surg. 2018; 28: 3783-3794https://doi.org/10.1007/s11695-018-3450-2 Crossref PubMed Scopus (678) Google Scholar ], accounting for $172.74 billion in annual expenditures [ 3 Ward Z.J. Bleich S.N. Long M.W. Gortmaker S.L. Association of body mass index with health care expenditures in the United States by age and sex. PLoS One. 2021; 16e0247307https://doi.org/10.1371/journal.pone.0247307 Crossref Scopus (77) Google Scholar ] with the medical costs for adults with obesity being $1861 higher than those with healthy weight [ 4 Ward Z.J. Bleich S.N. Long M.W. Gortmaker S.L. Association of body mass index with health care expenditures in the United States by age and sex. PLoS One. 2021; 16e0247307https://doi.org/10.1371/journal.pone.0247307 Crossref Scopus (111) Google Scholar ]. Similar trends are present in Europe [ 5 World Health Organization WHO European regional obesity report 2022. World Health Organization. Regional Office for Europe, 2022 Google Scholar ]. Importantly, it is estimated that overweight status (including obesity) is the fourth most common risk factor for non-communicable chronic diseases [ 6 WHO WHO European regional obesity report 2022. WHO Regional Office for Europe, Copenhagen2022 Google Scholar ]. The very high number of subjects with obesity advances the issue of whether all subjects need to be treated. At the same time, appreciating the heterogeneity within the obese population raises questions regarding what would be the best prevention, diagnosis, and management options and eligibility criteria in terms of efficacy and cost-effectiveness.