By Karen L. Kier
Pharmacist on behalf of the ONU Healthwise Team 

In Monty Python’s The Meaning of Life, there is a scene where Mr. Creosote explodes after eating too much food and being offered one thin wafer. The movie was released in 1983 after success with their other movies. 

The British comedy troupe formed in 1969 and started a comedy series on the British Broadcasting Corporation (BBC). The Monty Python’s Flying Circus was viewed from 1969 to 1974. The group’s comedy style was considered revolutionary. In 1988, the group won a BAFTA for their influence on comedy.

After holiday meals, one might express a feeling of fullness. We are entering the time of year when individuals are considering weight loss and thinking about New Year resolutions. 

The news for the last year has focused on the weight loss drugs referred to as glucagon-like peptide 1 (GLP-1) agonists. These include liraglutide (Saxenda®), semaglutide (Wegovy®), and the newest, tirzepatide (ZepboundTM). These agents are FDA-approved for weight loss. 

They are often recognized by their brand names with the same ingredients approved for treatment of diabetes. Liraglutide is Victoza® and is a once-daily injection. Semaglutide is also known as Ozempic® as an injectable and Rybelsus® as a tablet. Tirzepatide was approved for diabetes as MounjaroTM. 

GLP-1 agonists mimic the natural hormone in the body to lower blood glucose, which is why they can manage type II diabetes. They slow the emptying of food out of the stomach, which causes a feeling of fullness and decreases appetite. GLP-1 receptors are found in the brain and help regulate appetite as well.

Tirzepatide has an additional mechanism of action besides being a GLP-1 agonist. The additional activity is due to gastric inhibitory polypeptide (GIP). The combination of the GLP-1 and GIP within the clinical studies resulted in about a 15.7% weight loss, which is an average of 34.4 pounds. This was compared to a 3.3% weight loss in the placebo group. 

Other investigational studies evaluating new drugs for weight loss include oral semaglutide (Rybelsus®) at higher doses than currently approved for diabetes therapy. Lilly is studying a drug with GIP, GLP-1, and a third action known as retatrutide and early clinical trials demonstrate close to a 17% weight loss in 24 weeks. This drug is not FDA approved and more clinical studies need to be completed before seeking approval. 

These weight loss numbers are impressive and there has been a large demand for these products. The demand has exceeded the supply in many cases and shortages have existed. Another concern has been affordability. In addition, some unethical suppliers have been advertising and compounding unsafe medications with warnings being issued by the FDA to be cautious (FDA October 31, 2023). 

Some additional safety concerns have been issued. 

In June of 2023, the American Society of Anesthesiologist (ASA) warned healthcare professionals and the public about some dangers of using GLP-1 agonists before surgery. When going into surgery, it is important to be fasting with no food or liquids in the stomach. The risk of developing pneumonia after surgery is increased if food or liquids reflux up to the lungs during the procedure. The physicians were finding patients on the GLP-1 medications still had food in their stomach even after long periods of fasting. The ASA recommends stopping the GLP-1 at least one week prior to surgeries. 

In July of 2023, the European Medicines Agency released a warning about 100 case reports of possible self-harm or suicidal thoughts in patients taking liraglutide or semaglutide. As of September 28, 2023, the FDA is evaluating 265 reports of suicidal ideation with GLP-1 drugs for either weight loss or diabetes. 

On September 28, 2023, the FDA required labeling changes for the GLP-1s to include the risk of intestinal blockage also known as ileus. The FDA has received over 8,500 reports of gastrointestinal side effects with the GLP-1 class. Thirty-three reports were for ileus and this included 2 deaths.   

As with other weight loss options, individuals are likely to regain weight once they stop a GLP-1 drug. One manufacturer notes most patients will gain about ½ of their original weight back over the next 2 to 3 years after stopping the drug. Right now, there is no good evidence on the best way to handle the regained weight. The thought process is these drugs may become more long-term. 

The GLP-1 drugs are not considered safe in pregnancy and women need to stop the drugs at least 2 months before getting pregnant. Interestingly, one of the effects of losing weight can be an increase in fertility with unexpected pregnancies occurring. In addition, the package labeling for tirzepatide indicates a drug-drug interaction with oral birth control pills making them less effective, requiring an alternative method of contraception. 

Weight loss can be vital in improving our overall health!  It is important to talk to your pharmacist or healthcare professional about the pros and cons of GLP-1 agonists.

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