Abstract:
Glucagon-like peptide-1 (GLP-1) receptor agonists have shown promise in managing metabolic disorders such as diabetes and obesity. However, their potential off-label benefits in overweight individuals with underlying conditions such as hypertension (HTN), hypercholesterolemia (HCL), cardiovascular disease (CVD), anxiety, depression, bipolar disorder (BD), and colorectal cancer (CRC) warrant exploration. This paper aims to review the existing literature on the off-label benefits of GLP-1 drugs and propose a structured approach to their use in clinical practice.
Introduction:
GLP-1 receptor agonists, initially developed for the treatment of diabetes, have demonstrated efficacy in promoting weight loss and improving metabolic parameters. Given the prevalence of obesity and its associated comorbidities, there is growing interest in investigating the potential off-label benefits of GLP-1 drugs in addressing a range of health conditions. This paper seeks to explore the therapeutic implications of GLP-1 agonists in overweight individuals with various underlying conditions, considering the cost-benefit balance and safety considerations.
Methods:
A comprehensive literature search was conducted to identify studies examining the effects of GLP-1 drugs on the aforementioned conditions. Relevant articles published in peer-reviewed journals were included in the review. Additionally, insights from our master thesis titled “Off-Label Repurposed Use Of Tirzepatide In Overweight Non-Diabetic Patients With A Weight-Related Comorbidity” were incorporated to inform the proposed approach to the use of GLP-1 agonists in clinical practice.
Results:
GLP-1 receptor agonists have shown potential off-label benefits in addressing various metabolic and non-metabolic conditions:
- Hypertension (HTN): GLP-1 drugs may lead to weight loss, which can help reduce blood pressure in overweight individuals. Additionally, GLP-1 receptor agonists may have direct vasodilatory effects, contributing to blood pressure reduction.
- Hypercholesterolemia (HCL): GLP-1 agonists may improve lipid profiles by reducing LDL cholesterol and triglyceride levels and increasing HDL cholesterol levels. The weight loss associated with GLP-1 drugs may further improve lipid parameters in overweight individuals with hypercholesterolemia.
- Cardiovascular Disease (CVD): GLP-1 receptor agonists have shown cardiovascular benefits, including reducing the risk of major adverse cardiovascular events (MACE) and improving endothelial function. Weight loss and improvements in metabolic parameters may contribute to reducing the risk of CVD in overweight individuals.
- Anxiety and Depression: GLP-1 agonists may have neuroprotective effects and modulate neurotransmitter systems involved in mood regulation, potentially alleviating symptoms of anxiety and depression. Additionally, weight loss associated with GLP-1 drugs may also improve self-esteem and mood in overweight individuals.
- Bipolar Disorder (BD): While direct evidence is limited, the weight-reducing effects of GLP-1 drugs may be beneficial for individuals with bipolar disorder, who often face challenges related to weight gain and metabolic health.
- Colorectal Cancer (CRC): GLP-1 agonists may have potential anticancer effects by inhibiting cell proliferation and promoting apoptosis in CRC cells. Furthermore, weight loss induced by GLP-1 drugs may reduce the risk of CRC in overweight individuals, as obesity is a known risk factor for this type of cancer.
- Other Cancers: GLP-1 agonists may have anticancer effects in other obesity-related cancers, such as breast cancer, pancreatic cancer, and liver cancer. Weight loss and improvements in metabolic parameters could contribute to reducing the risk or progression of these cancers in overweight individuals.
- Overall Metabolic Health: GLP-1 agonists can improve overall metabolic health by promoting weight loss, reducing insulin resistance, and improving glucose control. These metabolic benefits may have a positive impact on various underlying conditions associated with obesity, leading to overall improved health outcomes.
Discussion:
While the off-label use of GLP-1 drugs holds promise, it must be approached cautiously. We propose the development of an algorithm similar to our master thesis, which outlines criteria for the judicious use of GLP-1 agonists in overweight individuals with underlying conditions. Validation by a qualified healthcare professional specializing in endocrinology and regular follow-up visits, including comprehensive metabolic panel monitoring, are essential components of this proposed approach.
Conclusion:
In conclusion, the off-label benefits of GLP-1 drugs in overweight individuals with various underlying conditions offer a promising avenue for further research and clinical practice. However, careful consideration of the risk-benefit balance and structured approaches to their use are necessary to ensure optimal patient outcomes. Future studies are needed to validate the proposed algorithm and elucidate the long-term effects of GLP-1 agonists in off-label indications.
This paper provides a comprehensive overview of the potential off-label benefits of GLP-1 drugs and proposes a structured approach to their use in clinical practice, emphasizing the importance of validation by healthcare professionals and regular monitoring of patient outcomes. It is now ready for publication and peer review.
Dr. Pete DO (Resident) 