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Battle Of The Bulge

Glucagon-Like Peptide 1 Agonist

GLP-1 is a hormone produced in the gut that is released in response to food. It causes reduced appetite and the release of insulin to utilize or store the energy ingested. It also has positive changes on how fat is metabolized. An agonist is a molecule that is similar enough to the real hormone that it causes similar effects at the cellular level as the real thing. So, a GLP-1 agonist is a molecule that acts like GLP-1 in your body.

Battle of the Bulge and the GLP-1 Agonist

A new era of weight loss pharmacotherapy has arrived with the introduction of GLP-1 agonists. The two main players are Novo Nordisk’s Semaglutide, aka Ozempic/Wegovy, and Lilly’s Tirzepatide, aka Mounjaro/Zepbound. When Semaglutide as Wegovy was approved in 2021, it had been almost 10 years since a medication was FDA approved for weight loss. And now Tirzepatide or Zepbound has been approved. Both have proven to be at least twice as potent for weight loss than prior appetite suppressants at 3 months, 6 months, 12 months, and up to 2 years from study findings. The findings are amazing and have the potential to be game changers for many who have endlessly struggled with their weight.

Wegovy created quite the buzz when the before and after pictures of Elon Musk came out after he had been taking it for a few months and the buzz has only grown since then, for good reason. I first wrote about my thoughts on their use for weight loss over a year ago and I have personally witnessed some remarkable results using the medications for weight loss as well as diabetes. Over the past year, a lot of new and interesting data and research have come out on their use. To say the least, this class of medications is proving to be worth the hype both good and bad – but mostly good. These medications have the potential to be huge game changers for many people that suffer from obesity and the associated health consequences like diabetes, heart disease, fatty liver, metabolic syndrome, and sleep apnea, as well as arthritis, depression and anxiety. Losing weight makes you feel good!

What is a GLP-1 agonist and what does it do?  

A Glucagon-Like Peptide-1 receptor agonist is a hormonal peptide medication that binds to the GLP-1 receptor and acts like GLP-1, an incretin, which upregulates insulin secretion and down regulates glucagon to help lower the glucose level in the blood. BUT, it also slows gastric emptying and signals the brain there is food in the stomach and to stop eating. In other words, it reduces hunger and cravings between meals as well as makes you feel fuller for longer after meals. Sounds like the perfect weight loss drug, right? 

What is a GIP agonist and why might it matter?

GIP receptor agonists are a new class of drugs for diabetes. GIP stands for glucose-dependent insulinotropic polypeptide. It’s a natural incretin hormone that plays a role in lipid metabolism and fat deposition. It works by enhancing appetite suppression, improving white adipose tissue health and storage capacity and reducing lipid spillover ectopic fat accumulation like in the organs like fatty liver disease. Why it matters is Tirzepitide has it and Semaglutide doesn’t. Small potatoes? Maybe or maybe not.

How good are the results?

For Zepbound, over the course of 72 weeks the average loss on the highest dose was 20.9% of body weight compared to about 3.1% for placebo and more than 91% of people lost at least 5% versus 35% for placebo. For Wegovy, after one year of use, 66% lost at least 10% of their body weight versus 10% for placebo and 48% lost at least 15% versus 3% for placebo. Both the medicated and the placebo groups were told to maintain a calorie restricted diet 500 calories below their estimated daily calorie expenditure and exercise at least 150 minutes per week.   

Side effects?

The most common side effects are gastrointestinal symptoms like nausea, diarrhea, constipation, heartburn, and indigestion in about 10-20% of people. However, these side effects were mild and resolved with subsequent injections.  Other common side effects are headache, nasal congestion and injection site reactions. Overall, only about 5-7% discontinue the medications due to side effects. So, the GLP-1 agonists are generally well tolerated.

When should you stop?

You can expect some weight to come back on but that all depends on your ability to eat better and move a little more.  When you stop, you will likely be in a much better position to navigate the good habits from the not so good habits. Or at least we hope so. Most people can manage to keep most of the weight lost off after stopping.

Do I have to stop the medication?

Early indications are looking good up to 4 years out at least for maintaining most of the loss or maybe shedding more if you stay on the medications. Plus, cholesterol improves, blood pressure improves and your cardiovascular risk is reduced through weight loss, and maybe even a little extra value from just being on the GLP-1 agonist.


Outrageous.$1500 to $1800 per month and currently they are in limited supply and hard to get. 

What about the cheaper compounded equivalents?

Yes, they are cheaper… but are you getting what you paid for? Not all compound pharmacies and products are the same and the FDA has already warned about the Semaglutide and Tirzepatide salts which may be a problem and are different from the real thing. You want to make sure you are getting it from a high-quality compound 503B pharmacy. Why? 503B pharmacies are the only compounding pharmacies that are able to provide office-use medications. A 503B pharmacy is a designation created by the FDA that establishes a new level of patient care and safety. 503B pharmacies must comply with strict CGMP (current good manufacturing practices) guidelines, the same standards pharmaceutical manufacturers are held to.

Are there more indications to come?

Probably. These medications are also in phase trials for other indications including sleep apnea, fatty liver, cardiovascular disease, and heart failure beyond their FDA approved indications for obesity and diabetes. From what has been resulted to date and what I have seen clinically, I would not bet against their success for these indications. 

More competition?

Oh yeah! Not only coming from both Novo Nordisk and Eli Lilly including oral versions, but also from big boys like Pfizer, Roche, Merck and AstraZeneca as well as some smaller players like Viking Therapeutics. Everyone wants a piece of this $50-100 billion market. Weight loss is in big demand and currently you are going to have to pay up to get the good stuff.   

Bottom Line:

The GLP-1 agonist Semaglutide and Tirzepatide are wonder drugs compared to prior obesity medications and likely have added value for other indications, especially decreasing cardiovascular risk. In general, most people tolerate them very well, with some patients having GI side effects with the first one or two doses that is tolerable and resolves with more injections. Brand is the better option if you can afford it, but if not, compounding from a select few compound pharmacies under a direct physician’s care is a safe option. However, always avoid the online approach to getting your compounded product given the potential unknowns. And lastly, if I had to pick a winner in the battle of the heavy weights, I would go with Tirzepatide given added GIP kick – but only by 1/10th of a love handle.