Get the Skinny on Weight Loss Drugs: The Latest Study on GLP-1 Receptor Agonists
The rise of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as treatments for diabetes and obesity has been remarkable, yet their comprehensive effects on health outcomes remain inadequately explored. Today we will examine a significant study utilizing the U.S. Department of Veterans Affairs databases, which involved over 2 million participants. The research aimed to compare the health outcomes of individuals using GLP-1RAs against those using other diabetes medications. Key findings indicate both benefits and risks associated with GLP-1RA usage, providing valuable insights for healthcare professionals and patients alike.
In recent years, medications like Ozempic and Wegovy, which belong to the class of drugs known as glucagon-like peptide-1 receptor agonists (GLP-1RAs), have gained immense popularity for their weight loss and diabetes management capabilities. Often referred to as “miracle drugs” in the media and among the patients, these injectable medications have shown promise in inducing substantial weight loss and improving metabolic health. However, the understanding of their broader effects on various organ systems has been limited until yesterday when this data was released.
This study conducted by researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care System has provided a comprehensive evaluation of the health outcomes associated with GLP-1RAs. This research analyzed a vast dataset to uncover both the positive and negative consequences of these medications, shedding light on their implications for clinical practice.
The study, published in the journal Nature Medicine, involved a cohort of over 2 million veterans diagnosed with diabetes. Researchers compared the health outcomes of individuals who initiated GLP-1RA therapy (n = 215,970) with those who started treatment with sulfonylureas (n = 159,465), dipeptidyl peptidase 4 (DPP-4) inhibitors (n = 117,989), and sodium-glucose cotransporter-2 (SGLT2) inhibitors (n = 258,614). A control group was also established, consisting of individuals continuing the use of non-GLP-1RA antihyperglycemics (n = 1,203,097), allowing for a more nuanced understanding of the medications’ effects.
The researchers aimed to assess a wide range of health outcomes—175 in total—across various organ systems. This approach allowed them to systematically map the implications of GLP-1RA usage compared to other standard diabetes treatments.
Key Findings
Potential Benefits of GLP-1RA Usage:
– Cognitive and Behavioral Health Improvements: Patients using GLP-1RAs exhibited reduced risks of seizures, substance use disorders (including alcohol and opioid addiction), and psychotic disorders. Notably, there was a decrease in neurocognitive disorders such as Alzheimer’s disease and dementia.
– Cardiometabolic Advantages: The study confirmed that GLP-1RAs are associated with a lower risk of cardiovascular events, including heart attacks and strokes, aligning with previous research findings.
– Reduced Inflammation: GLP-1RAs may help alleviate inflammation in the brain, leading to improved brain health and potentially mitigating neurodegenerative diseases.
Notable Risks to be concerned about that are Associated with GLP-1RA Usage:
– Gastrointestinal Complications: Users of these medications reported an increased risk of gastrointestinal issues, such as nausea, vomiting, diarrhea, and, in some rare cases, stomach paralysis.
– Pancreatitis and Kidney Concerns: One of the more serious findings was the association between GLP-1RAs and adverse effects on the pancreas and kidneys. Although these complications are uncommon, they can be extremely serious. Healthcare Providers and Physicians are advised to remain vigilant for symptoms of pancreatitis and to monitor kidney function in patients taking these medications.
The findings from this extensive study provide essential insights into the dual nature of GLP-1RAs. While they offer numerous benefits, particularly in terms of cognitive health and metabolic improvements, the associated risks cannot be overlooked and these drug’s should not be considered as a “risk free miracle”.
Dr. Ziyad Al-Aly, the study’s senior author, emphasized the importance of understanding the full spectrum of effects these medications can have on the body. “Given the drugs’ newness and skyrocketing popularity, it is vital to systematically examine their effects on all body systems,” he stated. The comprehensive analysis serves to inform both clinical care and future research directions.
The demand for GLP-1RAs has soared in recent years, with reports indicating that one in eight Americans has used or is currently using these drugs for conditions such as diabetes, heart disease, or obesity. The surge in popularity can be attributed to their effectiveness in promoting significant weight loss and improving overall health outcomes. However, it is crucial for patients and healthcare providers to engage in informed discussions about these medications, weighing the associated benefits against the risks.
The recent study on GLP-1 receptor agonists provides valuable insights into the complex landscape of weight-loss medications. While these drugs demonstrate considerable promise in enhancing cognitive health and reducing cardiometabolic risks, they are not without potential downsides. The findings underscore the necessity for healthcare professionals to closely monitor patients on these medications for signs of adverse effects, particularly concerning the pancreas and kidneys.
As the landscape of obesity and diabetes treatment continues to evolve, it is imperative to prioritize patient education and informed decision-making. Understanding the full range of effects associated with GLP-1RAs will empower patients and clinicians to make choices that best support long-term health and wellbeing.
- Possible thyroid tumors, including cancer. Tell your health care provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rodents, Ozempic and medicines that work like Ozempic caused thyroid tumors, including thyroid cancer. It is not known if Ozempic will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people
- Do not use Ozempic if you or any of your family have ever had MTC, or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- You or any of your family have ever had MTC or if you have MEN 2
- You are allergic to semaglutide or any of the ingredients in Ozempic. See symptoms of serious allergic reaction in “What are the possible side effects of Ozempic ?”
Before using Ozempic, tell your health care provider if you have any other medical conditions, including if you:
- Have or have had problems with your pancreas or kidneys.
- Have a history of diabetic retinopathy.
- Are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation)
- Are pregnant or breastfeeding or plan to become pregnant or breastfeed. It is not known if Ozempic will harm your unborn baby or passes into your breast milk. You should stop using Ozempic 2 months before you plan to become pregnant
Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, herbal supplements, and other medicines to treat diabetes, including insulin or sulfonylureas.What are the possible side effects of Ozempic?
Ozempic may cause serious side effects, including:
- Inflammation of your pancreas (pancreatitis). Stop using Ozempic and call your health care provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back
- Changes in vision. Tell your health care provider if you have changes in vision during treatment with Ozempic
- Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Ozempic with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include: dizziness or lightheadedness, blurred vision, anxiety, irritability or mood changes, sweating, slurred speech, hunger, confusion or drowsiness, shakiness, weakness, headache, fast heartbeat, and feeling jittery
- Kidney problems (kidney failure). In people who have kidney problems, diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems to get worse. It is important for you to drink fluids to help reduce your chance of dehydration
- Serious allergic reactions. Stop using Ozempic and get medical help right away if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue, or throat; problems breathing or swallowing; severe rash or itching; fainting or feeling dizzy; or very rapid heartbeat
- Gallbladder problems. Gallbladder problems have happened in some people who take Ozempic. Tell your healthcare provider right away if you get symptoms which may include: pain in your upper stomach (abdomen), fever, yellowing of the skin or eyes (jaundice), or clay-colored stools
- Food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). Ozempic may increase the chance of food getting into your lungs during surgery or other procedures. Tell all your healthcare providers that you are taking Ozempic before you are scheduled to have surgery or other procedures
The most common side effects of Ozempic may include nausea, vomiting, diarrhea, stomach (abdominal) pain, and constipation.
References
– Xie Y, Choi T, Al-Aly Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. *Nature Medicine*. Jan. 20, 2025. DOI
This research was funded by the U.S. Department of Veterans Affairs. No conflicts of interest relevant to this article were reported.
About Washington University School of Medicine
Washington University School of Medicine in St. Louis is a leading institution in academic medicine, encompassing a robust portfolio of biomedical research, patient care, and educational programs. With over 2,900 faculty members, the institution is committed to advancing medical knowledge and improving health outcomes through innovative research and training.
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