Editorial: Pharmacotherapy for Obesity in Persons With Inflammatory Bowel Disease

Historically, obesity has been managed by a variety of surgical procedures performed to bypass the stomach and facilitate early satiety. For many years, the use of pharmacotherapy has been limited by costs, effectiveness, and medication’s adverse events, resulting in lower rates of utilization. Up until 2018, the United States Federal Drug Administration (US FDA) had approved only 5 medications for the treatment of obesity–lorcaserin, orlistat, latrexone–buproprion, phentermine–topiramate, and liraglutide.¹ More recently, considerable research and public interest has been injected into novel pharmacotherapies for the management of obesity, with encouraging outcomes on overall weight reduction, and more modest and less robust data on the impact on cardiovascular health and the metabolic syndrome.¹

The impact of obesity on patients with inflammatory bowel disease (IBD) has been examined in the past, with reported prevalence between 15% and 40%.² While the effects of peripheral adiposity have been shown to influence IBD-related outcomes, there have been conflicting studies on the effect of obesity in response to therapy, IBD-health-related outcomes, and surgeries.^2–6 Given the conflicting data over the years, along with the increasing prevalence of both IBD and obesity, a recent update on the overall burden of obesity in the United States and an insight into the use of anti-obesity pharmacotherapy has been lacking.

Elangovan et al⁷ highlighted the burden of obesity in a large cohort of adults with IBD in the United States. They reported a low rate of uptake and utilization of anti-obesity pharmacotherapy. This retrospective analysis utilized a commercially available database of 64 million American adults and gathered deidentified information on inpatient and outpatient visits, medication use and demographics over a recent 10-year period. The authors reported a high burden of obesity among IBD patients with a prevalence of 37 300 per 100 000 persons. Metabolic disorders including type 2 diabetes mellitus (14.3%), hypertension (37.2%), hyperlipidemia (34.2%), and obstructive sleep apnea (11.8%) were reported, with a higher prevalence in those with ulcerative colitis (UC) over Crohn’s disease (CD). Despite these high rates of metabolic comorbidities and prevalence of obesity within the IBD population, utilization of anti-obesity pharmacotherapy was exceedingly scarce among this population, with reported rates of merely 2.8%. When examining the trend analysis, however, the rates of anti-obesity prescribing in IBD patients increased nearly 3-fold, from 1.4% in 2010 to 3.6% in 2019, suggesting there currently may be more attention being paid to the use of these medications in this population that originally thought.

The low utilization of pharmacotherapy in this population may be secondary to the perceived notion that these patients are often malnourished, and weight loss may not be in their best interest. A number of studies have shown quite the contrary, however, suggesting that obesity (and more specifically, peripheral visceral adiposity) may contribute to both the development and perpetuation of IBD as a result of an ongoing, chronic inflammatory burden.^2,8 Furthermore, it has been well reported that obesity can negatively influence relapse rates, quality of life and hospitalization in IBD, thereby making the management of obesity in these patients critical. Recent studies have reported that obesity does not play a role in infectious complications in biologic users, or on disease progression in either CD or UC patients.^1,6 As a gastroenterologist’s biggest concern may be malabsorption and weight loss within this population, it is not surprising that management of an obese patient is not at the forefront of a clinical visit. Apart from a lack of awareness on the burden of obesity within the population, Elangovan et al speculate that lack of insurance, differences in provider training and limited experience prescribing anti-obesity medications may also influence the low rates of overall prescribing. As these are common reasons for low rates of prescribing within the general population, it is entirely reasonable to assume these same barriers may be present in an IBD practice.

Interestingly, the effects of anti-diabetic GLP-1 (glucagon-like peptide-1) receptor therapies have been studied in an IBD population. Liraglutide, an FDA approved anti-obesity medication, is a common GLP-1 receptor agonist used in the management of diabetes. Villumsen et al⁹ report a reduced risk of adverse IBD-related clinical events (including need for oral corticosteroids, tumor necrosis factor [TNF] alpha inhibitors, hospitalizations, or IBD-related surgeries) in a Danish cohort treated with GLP-1-based therapies, suggesting these medications may influence disease activity.⁹ This may be a direct result of GLP-1 on reduced circulating C-reactive protein and anti-TNF alpha.¹⁰ Further research is currently underway on the potential role GLP-1 receptor therapies may play in the management of intestinal inflammation.

Elangovan et al report a significantly higher prevalence of all metabolic comorbidities in UC patients as compared with CD. The impact of anti-obesity medications on lowering the cardiometabolic risk profile has been shown to be only modest in 1 large systematic review by Khera et al.¹ Greuter et al showed an increase in disease activity among obese CD patients, but not UC patients, however found no correlation with disease progression or treatment failure.⁶ This further begs the question as to whether treatment of obesity within the IBD population would truly benefit their overall disease course. In addition, it is becoming more discernible that the answer to this question should be postulated to both CD and UC as distinct entities.

Elangovan et al outline an important topic on the management of patients with IBD. As the rates of both IBD and obesity continue to increase, further research is necessary to determine the benefits that anti-obesity pharmacotherapy may have on the overall disease outcomes and metabolic risk factors in an IBD population. Of critical importance is understanding these potential effects on each IBD phenotype, independent of one another, given our knowledge on the predisposition of obesity in UC as compared with CD. This will, and should, become a topic of interest in the future research realm of IBD.

Funding

None declared.

Conflicts of Interest

W.E.-M. holds the position of Associate Editor for Crohn’s & Colitis 360 and has been recused from reviewing or making decisions for the manuscript.

Data Availability

NA as this is an editorial article.