The Weight Loss Shots

What is GLP1?

GLP1 stands for Glucagon-Like Peptide 1, which is a hormone we naturally make in the intestines and to a lesser extent, the brain.  This is released upon contact from macronutrients: carbohydrates, fat and protein.

How does it work?

It has many downstream effects, as most hormones do, but in regard to blood sugar it decreases blood sugar by helping the pancreas release insulin.  This insulin then allows glucose to leave the bloodstream and enter the cells where it can function.  GLP1 also decreases the amount of glucose made or released from the liver, again leading to an overall decreased amount of glucose in the bloodstream.

GLP1 also slows gastric emptying, meaning it slows the process of digesting your food.  Essentially food will “sit” for longer before moving through.  This leads to feeling full (called satiety), thereby decreasing total food and caloric intake and thus weight loss.

Why is the medication used and why has it become so popular?

With such an exponential increased rate of diabetes in the population, many newer medications have come to market in the past few decades.  Just as an interesting side note, insulin was only discovered and put to use as a medication about 100 years ago.

In 2005, the first of the GLP1 agonists called Exenatide (brand name Byetta) was brought to market.  It was synthesized from saliva of a Gila monster (how could I not add that fact to this blog article?!).  The next was in 2010 called Liraglutide (brand name Victoza).  These medications were very effective at reducing the hemoglobin A1C measurement in diabetics, reducing blood glucose including after meals (when we typically see a glucose spike).

These medications were initially studied in the diabetic population.  Only recently have they been studied for weight loss (and other purposes) in patients without diabetes.

You’ve probably heard or seen in the news some discussion of “weight loss drugs” or the “weight loss shot”, these are the medications they are discussing.

What are the medications?

What are the benefits?

In addition to the above glucose metabolism benefits, GLP1 agonists have shown heart healthy benefits such as decreased blood pressure and improved cholesterol profiles.

What are the risks?

Initial trials with exenatide showed an increase in pancreatitis, thought to be induced by the medication itself.  This led the FDA to include a warning on this class of medications that they may lead to pancreatitis.  These medications should probably be avoided in anyone with a history of pancreatitis and should be stopped in someone who develops pancreatitis.

Mouse models shows an increased risk of thyroid cancer, specifically medullary thyroid cancer.   In someone with a personal or family history of this cancer, these medications should be avoided.

What are the side effects?

The most common side effects are gastrointestinal in nature: nausea, vomiting, diarrhea, constipation.  If we recall how the GLP1 hormone works, it’s released from the intestine and slows the digestive system.  The food is sitting for longer, leading to these side effects which can be very common with the use of these medications.

What’s my take?

My take is these medications can be a useful tool.  Of course the improvement of blood glucose, insulin sensitivity, weight measurements, blood pressure, and all the other downstream effects of GLP1 is desirable, in diabetics and non-diabetics.  I also believe this is not addressing the root cause of such prevalent and grave metabolic dysfunction in the general population.

An interesting part of how the widespread use of these medications has affected clinical practice is actually related to anesthesia.  The reason you’re told to not eat or drink after midnight before a surgery (though this has largely changed, allowing some liquids in the hours pre-procedure) is due to the risk of aspirating your stomach contents during intubation.  Again if we recall that food will sit in the stomach longer while taking a GLP1 agonist medication, this increases the risk of aspiration.  At the hospital where I work (and across the nation), there are guidelines to have patients stop their GLP1 agonist medication long before the procedure (for a weekly medication, holding the week prior) to avoid that risk.

Additionally, for midlife women in particular, weight gain is a genuine concern both cosmetically and medically.  The weight gain tends to be around the abdomen and around the organs (visceral fat) which does have implications like increased cardiovascular risk.  Weight loss can be paramount in decreasing this risk and a GLP1 agonist medication can help.  However, weight loss does not discriminate between fat and muscle loss.  We do not want to lose muscle in midlife.  In fact, we want to be gaining it.

For someone who has already instituted a whole food, protein and fiber-rich diet and is exercising with a mix of “cardio” and weight training, who needs some help with weight loss, I think these medications can be appropriate, knowing that those lifestyle habits need to continue.

With that being said, my final take is these medications are not the first thing we reach for nor should they be the last.

Resources:

Some of the information contained in this article is the result of my training, medical knowledge, and personal experience without a specific source to be cited.

This is not medical advice.

Prasad-Reddy L, Isaacs D. A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond. Drugs Context. 2015 Jul 9;4:212283. doi: 10.7573/dic.212283. PMID: 26213556; PMCID: PMC4509428.

https://www.obgproject.com/2025/02/03/systematic-review-of-glp-1-ras-for-weight-loss-in-adults-with-overweight-obesity-without-diabetes/?mc_cid=caff7bfa69&mc_eid=d5f9bc71a4

Rodriguez PJ, Goodwin Cartwright BM, Gratzl S, et al. Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. JAMA Intern Med. 2024;184(9):1056–1064. doi:10.1001/jamainternmed.2024.2525