Authors reply: Obesity treatment in adolescents and adults in the era of personalized medicine

Dear Editor,

Our thanks go to Mazzetto et al. [1] for their interest in our paper on personalized obesity treatment, recently published in the Journal of Internal Medicine [2].

We welcome their comments on the interesting connection between obesity treatment and chronic cutaneous conditions, especially because these aspects are not commonly noted in clinical practice. At present, treatment with the new glucagon-like peptide-1 (GLP-1) receptor agonists is demonstrated to have beneficial effects on various conditions besides obesity and diabetes type 2, such as reducing the risk of worsened cardiovascular outcomes [3] and delaying the progression of diabetes-related nephropathy [4].

Obesity is characterized by a state of chronic inflammation. Thus, weight loss as such could be hypothesized to lead to inflammation improvement. Nonetheless, consistent evidence from both preclinical studies and clinical trials suggests that GLP-1 receptor agonists exhibit anti-inflammatory effects influencing the immune system, irrespective of glycemic state and even before significant weight loss occurs. These potential immunomodulatory effects of GLP-1 and its agonists introduce new possibilities for treating inflammatory diseases.

GLP-1 receptor agonists have been shown to be associated with a decrease of inflamed airways causing asthma attacks [5], to improve the inflammation in metabolic dysfunction-associated steatotic liver disease [6], and as Mazzetto et al. point out [1], a number of studies have also shown improvements in psoriasis, another inflammatory condition. This anti-inflammatory effect on chronic cutaneous conditions, such as psoriasis, has also been found after metabolic and bariatric surgery. GLP-1 levels substantially increase postoperatively, suggesting that the response is GLP-1 mediated.

In the Swedish Obese Subjects study comparing persons who had metabolic and bariatric surgery to controls with obesity, none had psoriasis at baseline. However, during 25 years of follow-up, metabolic and bariatric surgery were associated with a lower incidence of psoriasis, HR: 0.65 [0.47–0.89] [7]. Interestingly, a longer duration of obesity was independently associated with a higher risk for psoriasis, thus supporting that chronic inflammation is a risk factor. However, the degree of weight loss seems important, as gastric bypass surgery reduced both the risk of new-onset psoriasis (adjusted HR 0.52 [0.33–0.81]) and progression to severe psoriasis (adjusted HR 0.44 [0.23–0.86]) in a population-based Danish study, whereas gastric banding—resulting in lower weight loss—demonstrated a slightly increased risk for both conditions with time [8].

In this context, we would also like to remind all readers of the frequent need for excess skin removal after successful obesity treatment with significant weight loss to avoid cutaneous conditions such as skin infections and fungal rashes [9].

In summary, besides the well-known effect on weight and glycemic control, GLP-1 receptor agonists exert effects on a wide range of physiological and pathological processes, including inflammation. It is essential that specialists—beyond those managing obesity and diabetes—consider these medications as adjuncts in the management or as a potential treatment option for their patients.

Kind regards from all authors.

Expert committee for the Swedish national guidelines for obesity care: all authors. Board members of the Swedish organization for obesity research: Kajsa Järvholm, Lovisa Sjögren, Paulina Nowicka, and Ylva Trolle Lagerros; the Swedish organization for childhood obesity: Kajsa Järvholm; the Swedish pediatric treatment registry: Lovisa Sjögren; the Scandinavian Obesity Surgery Registry: Magnus Sundbom. Local principal investigator in a global phase III study of a GLP-1/glucagon dual agonist for adults: Ylva Trolle Lagerros (part of clinical work). Local principal investigator in a global phase III study of a GLP-1 agonist for children: Lovisa Sjögren (part of clinical work). Lecturing fees from industry: Kajsa Järvholm (part of clinical work).