GULP! Let’s Talk About GLP-1 RA’s

GLP-1 therapies are revolutionizing the medical field, offering new treatment options for various chronic conditions. These therapies are changing the management of diseases like diabetes, obesity, cardiovascular diseases, kidney health, and neurodegenerative disorders through the use of GLP-1 receptor agonists. But at WHAT COST?

GLP-1 is a hormone primarily released in the intestines in response to food intake. It aids in glucose regulation by promoting insulin secretion and inhibiting glucagon release from pancreatic alpha cells.

Additionally, GLP-1 slows gastric emptying, enhances feelings of fullness, and reduces appetite, which helps decrease food consumption and contributes to weight loss and management.

Natural GLP-1 has a short half-life due to rapid degradation. Pharmaceutical GLP-1 receptor agonists are designed to mimic GLP-1 effects but with longer half-lives. These medications are FDA-approved for treating type 2 diabetes mellitus and, more recently, obesity. These therapies show substantial results in multiple areas:

• Cardiovascular Disease: Numerous cardiovascular outcome trials indicate that GLP-1 receptor agonists reduce major adverse cardiovascular events by up to 26% in patients with T2DM. They enhance several cardiovascular risk factors, including high blood sugar, obesity, hypertension, and dyslipidemia.

• Weight Loss: Studies consistently demonstrate positive weight loss outcomes. Depending on the drug and dosage, GLP-1 receptor agonists are linked to modest weight loss (≥ 5%) over 72 weeks of therapy. That's merely 10 lbs for a 200 lb person over a year on the medication. There are certainly safer and less costly options!

  
  

• Research published in the New England Journal of Medicine found that one-third of patients treated with semaglutide (Ozempic) lost at least 20% of their baseline weight at 68 weeks, comparable to weight loss typically seen 1-3 years after bariatric surgery. That's only about 1/2 lb a week for a year and a half.

  
  

• Diabetes: GLP-1 receptor agonists improve glycemic control, leading to average hemoglobin A1c (HbA1c) reductions of 0.72%. A study in the Journal of Diabetes Research evaluated the efficacy of GLP-1 receptor agonists in insulin-treated patients with T2DM and found that adding a GLP-1 agonist to insulin therapy significantly reduced HbA1c and insulin needs. However, a 0.72% reduction may not seem significant to everyone.

  
  

• Neurodegeneration: GLP-1 receptor agonists, by crossing the blood-brain barrier and affecting neuroinflammation, oxidative stress, and protein aggregation, show potential as a treatment strategy for neurodegenerative diseases. More research and clinical trials are necessary to fully explore this potential.

  
  

• Parkinson’s Disease: GLP-1 receptor agonists help reverse dopaminergic cell loss, restore dopamine synthesis, and improve motor function while also providing anti-inflammatory and oxidative stress protection.

  
  

• Substance Use Disorder: Besides modulating neuroinflammation and oxidative stress linked to addiction, GLP-1 receptor agonists also influence reward processing. Preclinical studies have shown that GLP-1 receptor agonists can reduce alcohol intake, decrease motivation to consume alcohol, and prevent relapse by potentially lowering alcohol-induced reward.

  
  

• Chronic Kidney Disease: A systematic review and meta-analysis of cardiovascular outcome trials showed that GLP-1 receptor agonists significantly reduce the risk of adverse kidney disease outcomes by 17% compared to placebo, primarily due to decreased albuminuria.

These medications are costly, with the monthly average wholesale price for GLP-1 receptor agonists ranging from $929 to $1,283. Insurance coverage varies widely. For diabetes management, manufacturer discounts for GLP-1 receptor agonists approved for T2DM range from 54% to 59%, resulting in net monthly prices of $312 to $469. However, for obesity management, discounts are lower, with net prices ranging between $717 and $761. That's your cost, per month!

Like all pharmaceuticals, GLP-1 receptor agonists come with several concerning side effects.

The most common include gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Other side effects include headache, dizziness, injection site reactions, and low blood sugar, as well as significant muscle mass loss. More serious side effects include pancreatitis, gallbladder disease, and complications related to diabetic retinopathy, particularly with semaglutide.

GLP-1 receptor agonists also carry a black box warning, indicating significant risks of serious or life-threatening side effects, such as thyroid C-cell tumors, including medullary thyroid carcinoma. They are contraindicated for patients with a personal or family history of these conditions or multiple endocrine neoplasia syndrome type 2.

The FDA warns against using unapproved GLP-1 receptor agonists for weight loss due to increased risks of adverse effects and dosing errors.

Some compounded semaglutide products are salt forms (semaglutide sodium or acetate), which have different active ingredients from the approved drugs, and there is no information about their safety and efficacy.

After weighing the benefits of these drugs against their cost and safety concerns, I believe there are better options. Many people use them for weight loss, but there are healthier, more affordable ways to achieve that without the risks. Contact me to discuss a customized meal plan. As with all health-related decisions, it's a personal choice. My role is to provide you with the data so you can make an informed decision.

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