Authors: Praveen Sundar, Erik Schraga, MD
INTRODUCTION
You can’t turn on the TV or open social media lately without hearing about the latest trend in weight loss, namely the GLP-1 RAs including Weygovy and Ozempic. Though these articles have thus far focused on the world of emergency medicine and urgent care, the questions and concerns about these medications have become pervasive throughout the medical field.
DRUG OVERVIEW
GLP-1 receptor agonists (GLP-1 RAs) are a relatively novel medication meant primarily to treat type 2 diabetes. However, the class of medications has been in extraordinarily high demand lately due to the secondary effect of weight loss. Even those without diabetes are finding that the medication can result in significant weight reduction without causing low blood sugar. The majority of these agents are given via injection, with the most common drugs being dulaglutide (Trulicity), semaglutide (Ozempic, Wegovy), and liraglutide (Victoza, Saxenda). Semaglutide (Rybelsus) is taken orally but with concern of lower effectiveness.
GENERAL USE
GLP-1 RAs function by mimicking the action of the human hormone GLP-1, which stimulatesinsulin production after eating and helps prevent spikes in blood sugar in diabetics. It is not clearly established how it results in weight loss, particularly in non-diabetics, but the likely explanation is that it helps to “delay gastric emptying,” thereby keeping the individual from feeling hungry. It is also shown to alter pancreatic activity to aid in the maintenance of blood sugar levels via insulin secretion. (1,2)
While GLP-1 RAs are mainly intended for type 2 diabetics, many non-diabetic patients have been using the drug for weight loss. The Mayo Clinic has found that various GLP-1 RAs can cause weight loss between 15.8 pounds and 33.7 pounds depending on the agent and starting weight. (3)
SIDE EFFECTS
The most common gastrointestinal side effects of GLP-1 RAs include nausea, vomiting, diarrhea, and abdominal pain. Starting at low dose and increasing gradually to an effective dose has been shown to reduce the potential for side effects.
- Nausea and diarrhea were common with more than 10% incidence (4)
- Vomiting, constipation, abdominal pain, and dyspepsia had between 1% and 10% incidence (4)
- Abdominal symptoms decrease after prolonged durations of treatment.
- GLP-1 use has also been linked with mildly increased heart rates, but is not linked with major cardiovascular events (4)
- Erythema (reddening of the skin), rash, and itching at the injection site are also prevalent, based on drug type and dosing schedules (4)
APPROVAL
While many GLP-1 RAs do help with weight loss, in the American market there are only two currently approved GLP-1 RAs FDA approved solely for weight loss: Saxenda and Wegovy. Both of these medications have been shown to be “twice as effective as older weight-loss drugs.” Saxenda and Wegovy have the identical ingredient to their diabetes counterpart (Victoza and Ozempic, respectively), but are dosed in a higher amounts. It should also be noted that “off-label” use of a medication not intended by FDA approval is a very common and accepted practice in the medical field.
COST
Cost remains the primary limitation for use of GLP-1 RAs. Insurance companies are declining to cover the use of these drugs for solely weight loss, as obesity is seen as a “lifestyle byproduct” rather than a disease.5 GLP-1 RAs are covered by insurance only if their intended use is to treat type 2 diabetes. Even for these patients there are often limitations with requirement of a trial of a less expensive medication first. Those who chose to pay out of pocket for medications such as Wegovy or Saxenda often have to pay upwards of $1,000 per month, though some pharmaceutical companies and pharmacies offer discounts to bring the price down to $700-800.
DOSING & EFFICACY
(SC refers to intake via subcutaneous injections, while PO refers to intake via oral pills)
Based on data collected by Trujillo et al., drugs like semaglutide (Ozempic, Wegovy) and liraglutide (Victoza, Saxenda) provide both the highest effect in aiding in type 2 diabetes and weight loss.
Both figures taken from Trujillo et al.
SOCIAL IMPLICATIONS
While production of the drug Wegovy was severely limited in 2022 and prevented numerous patients from receiving their doses, Novo Nordisk (Wegovy manufacturer) reports that they don’t foresee that problem in 2023. They claim to have increased their production capacity and are “closely monitoring prescribing trends and assessing demand.”6 Although not specifically approved for weight loss, Ozempic, has been commonly prescribed for weight loss and at this time is widely available. The ethical concern of taking a medication intended to reduce the serious effects of type 2 diabetes has been raised. If there were to be a shortage of Ozempic, those in need may not have access to the drug due to others using it for weight loss. Careful consideration must then be taken by weight loss patients during times of limited supply, reserving it for those most in need.
Sources:
1 – https://www.ncbi.nlm.nih.gov/books/NBK551568/
2 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063254/
4- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397288/
6 – https://www.novonordisk-us.com/products/product-supply-update.html
