The intersection of rheumatology and weight management is gaining increasing attention, particularly with the emergence of GLP-1 agonists and other weight loss medications. These drugs, initially developed for diabetes and obesity, are showing promise in managing rheumatic diseases like psoriatic arthritis and rheumatoid arthritis. This article explores the potential benefits, challenges, and future directions of prescribing weight loss medications in rheumatology.
The Growing Interest in Weight Loss Medications for Rheumatic Diseases
Recent studies and clinical observations suggest that weight loss can be an effective measure for patients seeking to manage autoimmune disorders. Specifically, medications like GLP-1 agonists are being considered for their potential to improve treatment response and overall health in patients with conditions like psoriatic arthritis (PsA) and rheumatoid arthritis (RA).
Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center and Providence-St. Joseph Health, noted that rheumatologists are "on the cusp of beginning to prescribe some of these themselves." He emphasized the importance of understanding these medications, including their efficacy, potential adverse effects, and the prior authorization process.
The Connection Between Obesity and Rheumatic Diseases
Obesity is increasingly recognized as a significant factor in the development and management of rheumatic diseases. For instance, in patients with psoriasis, obesity is considered a "biomarker and risk factor" for the development of psoriatic arthritis. Moreover, in individuals with PsA, obesity reduces the likelihood of achieving and maintaining a positive treatment response.
The relationship between arthritis, mental health, and weight is complex. People living with arthritis are more prone to conditions like depression and anxiety, a trend also observed in individuals with obesity. An arthritis diagnosis can significantly impact a person's daily life, self-perception, and social interactions. The presence of obesity alongside arthritis can exacerbate these challenges. Some individuals may turn to food as a coping mechanism for mental health issues arising from arthritis, leading to further weight gain, which, in turn, can worsen arthritis symptoms and overall mental well-being, creating a detrimental cycle.
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The Potential Benefits of GLP-1 Agonists
GLP-1 agonists, such as semaglutide (Wegovy, Ozempic) and liraglutide, mimic the activity of glucagon-like peptide-1 (GLP-1), a hormone that naturally occurs in the body. These medications regulate blood sugar and appetite after meals, promoting weight loss. Beyond their weight loss effects, GLP-1 agonists may also improve treatment response through their immunomodulatory effects. Studies have demonstrated that GLP-1 agonists can lead to "a reduction of various pro-inflammatory cytokines and acute phase reactants."
According to Mease, case reports have indicated that diabetes/weight loss drugs alone, without immunomodulatory therapy, could benefit patients with PsA. He shared an example of a patient referred for PsA evaluation who experienced improved arthritis symptoms and normal ultrasound results after losing 14 pounds on a weight loss drug.
Alexis Elias Malavazos, MD, PhD, and colleagues reported a case involving a patient with obesity and type 2 diabetes whose psoriasis had been unsuccessfully treated with guselkumab. The patient experienced a nearly 26% reduction in BMI and significant improvements in skin and joint scores after being treated with the GLP-1 agonist semaglutide.
Caution and Optimism
While these "n of 1" experiments should be viewed cautiously, Mease expressed optimism about the potential benefits of weight loss drugs across the spectrum of rheumatic diseases. He suggested that further research should focus on combination therapy with immunomodulatory drugs versus immunomodulatory drugs alone, emphasizing the "tantalizing potential for improving the pro-inflammatory cytokine milieu."
Rheumatologists' Perspectives on Weight Management
Rheumatologists are increasingly recognizing the importance of addressing obesity in their patients with arthritis. Emerging research indicates that obesity is associated with higher disease activity and a less favorable response to specific therapies in inflammatory conditions like rheumatoid arthritis and psoriatic arthritis.
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One survey assessing practitioner views on weight management in rheumatology revealed that the majority of respondents acknowledged the association between obesity and worse disease activity in rheumatoid arthritis. Nearly all agreed that it was at least partly their responsibility to help patients address excess weight. However, more than three-quarters of respondents felt not confident, or only slightly confident, in their ability to help patients achieve clinically meaningful weight loss.
The "Obesity First" Approach
The concept of treating obesity first to improve other conditions, termed the "obesity first" approach, is gaining traction. By directly addressing obesity, healthcare providers can potentially improve or even resolve associated conditions like type 2 diabetes, hypertension, and dyslipidemia. This holistic approach recognizes obesity as a root cause rather than a consequence, aiming to improve overall patient health and simultaneously reduce the burden of multiple chronic diseases.
However, some experts believe it is premature to adopt an "obesity first" approach for autoimmune diseases. While some patients with autoimmunity may experience positive results by focusing solely on obesity, this may not be the case for everyone. The biologic triggers for an individual's autoimmune disease are complex and personal, and addressing the underlying autoimmune disease is also crucial.
Prescription Weight Loss Medications: Options and Considerations
Several prescription weight loss medications are available, each with its own mechanism of action and potential benefits. These include:
- Liraglutide and Semaglutide: GLP-1 receptor agonists that mimic the activity of a natural hormone to regulate blood sugar and appetite.
- Bupropion-Naltrexone: A combination drug that provides a substantial weight loss benefit by affecting areas of the brain that control appetite and reward.
- Phentermine-Topiramate: Another combination drug that includes an appetite reducer (phentermine) and a medication used to treat seizures or headaches (topiramate).
- Orlistat: A lipase inhibitor that blocks the absorption of some dietary fats in the gut.
It is crucial to remember that these drugs are not a "one and done" treatment for overweight and obesity. They should be used in conjunction with lifestyle modifications, including diet and exercise.
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Lifestyle Modifications: A Cornerstone of Weight Management
While medications can play a significant role in weight loss, lifestyle modifications remain a cornerstone of effective weight management.
- Physical Activity: Exercise alone may not be the most effective strategy for long-term, sustainable weight loss. However, physical activity helps with weight maintenance and has numerous other health benefits. Exercise in arthritis improves pain, function, quality of life, and fatigue, is an effective treatment for depression, and reduces the risk of developing cardiovascular disease and diabetes.
- Nutrition: Instead of recommending specific short-term diets, healthcare providers should encourage patients to find healthy, long-term nutrition strategies that work for them. Prioritizing whole foods, mostly plants (vegetables, legumes, etc.), and lean protein sources (plant-based sources, fish, poultry, and dairy) is generally recommended. Minimizing processed foods is also important, while allowing for occasional treats or indulgences in moderation. A Mediterranean-style diet has strong evidence for improving overall health.
The Impact of Arthritis on Physical Activity and Mental Health
Arthritis can significantly impact a personâs ability to remain physically active. Joint pain, stiffness, and swelling can limit mobility and lead to a sedentary lifestyle. Living with a chronic condition like arthritis can also affect mental health, with conditions like depression and anxiety being more common. These factors can further complicate weight management efforts.
Complications of Arthritis and Obesity
People living with arthritis and obesity may face several complications, including:
- Obstructive Sleep Apnea: Excess fat tissue increases the risk of sleep apnea, reducing sleep quality and quantity.
- Cardiovascular Disease: Active inflammation from arthritis, combined with obesity, increases the risk of heart attacks, strokes, and blood clots.
- Metabolic Dysfunction-Associated Steatotic Liver Disease: Formerly known as non-alcoholic fatty liver disease, this condition can result from obesity.
- Fertility Issues: Obesity can reduce fertility in women, and weight loss can improve fertility.
Future Directions in Research and Clinical Practice
Further research is needed to fully understand the potential benefits and risks of using weight loss medications in rheumatology. Key areas of investigation include:
- The specific anti-inflammatory effects of GLP-1 agonists and their impact on autoimmune diseases.
- Identifying the types of autoimmune disease patients who would benefit most from this type of treatment.
- The effect of these medications on the microbiome and its impact on autoimmune disease.
- Determining the amount of weight loss needed to see a significant impact on rheumatic disease activity.
Moreover, there is a growing need for interdisciplinary clinics that provide comprehensive care for patients with rheumatic diseases and obesity. These clinics can offer comprehensive assessments, recommend tailored weight management strategies, and provide ongoing support to optimize the personâs health.
Emerging Therapies and Clinical Trials
Beyond GLP-1 agonists, other therapies are being explored for their potential in managing rheumatic diseases.
- F8-IL10 (Dekavil): A subcutaneously administered agent consisting of the anti-inflammatory cytokine interleukin 10 (IL-10) fused to a vascular targeting antibody. It is currently being studied to treat rheumatoid arthritis (RA).
- NB32 (Bupropion/Naltrexone, Contrave): An experimental obesity drug that has undergone FDA review.
- Certolizumab Pegol: An anti-TNF-α therapy approved for treating RA, psoriatic arthritis, and ankylosing spondylitis. A long-term clinical trial is evaluating its safety and efficacy in Crohnâs disease (CD).