GLP-What!? A Story of Serendipity that’s Shifting Paradigms in Obesity Treatment

You’ve probably heard the word Ozempic® somewhere on social media, TV news, or perhaps you even know someone taking this or a similar medication. But what are they? How do they work? Are they safe? And most importantly, who can benefit from them?

What Are GLP-1s and How Do They Work?

As the Greek physician and “Father of Medicine,” Hippocrates, said: “Nature itself is the best physician.” Glucagon-like peptide 1, or simply GLP-1, is a class of short-acting (1-2 minutes) hormones known as “incretins,” which are found in most vertebrate animals (including humans). In general, they help regulate metabolism, appetite, blood sugar levels, and gastrointestinal transit in response to meals. They were discovered in the early 1900s, but it wasn’t until the late 1990s that researchers found a similar version of incretins in the saliva of the Gila monster and developed a more stable, long-lasting version for use in humans.

These medications are analogues of the naturally produced GLP-1 in the human body and were initially used to treat type 2 diabetes, helping patients achieve healthier blood sugar levels. It wasn’t until 2009 that researchers, through serendipity, realized that besides improving blood sugar levels, GLP-1s had a significant effect on weight loss. This led to numerous studies that helped researchers develop new and better versions of these medications specifically for weight loss.

You’ve probably heard of someone who “lost tons of weight” on one of these medications and wondered how. Eating is one of the most complex vital processes in humans, involving constant communication between organs like the brain, gut, fat cells, and even muscles. This communication uses signals like hormones, neurotransmitters, and nerves to make you feel hungry or full. Yes, this regulatory process can be overridden by social, psychological, or cultural factors, like when you’re full but the server brings the dessert menu. GLP-1s are just one piece of a larger puzzle, but their effect on appetite and other metabolic processes is very robust.

In simple terms, these medications help you lose weight by curbing your appetite, making you eat less, and pushing your body to use energy from fat stores. While there are other important effects, like prolonging the time food stays in your stomach before continuing its transit, changing the way some things taste, helping your body use nutrients and energy stores more efficiently, and decreasing cravings, they all manifest as feeling less hungry.

Who Can and Cannot Take These Medications?

At this point, GLP-1s might sound like the long-desired solution to one of the biggest public health issues in the US. They are indeed revolutionizing the way we treat and even think about obesity. However, while they have many benefits, not everyone can take them, and they require a certified physician to prescribe them safely. Generally, patients with a body mass index (BMI) greater than 30 kg/m², or greater than 27 kg/m² with one or more obesity-related medical conditions (such as hypertension, diabetes, or sleep apnea), may be eligible.

Although these medications mimic a natural human process, they do have side effects and important contraindications to consider. The most common side effects are gastrointestinal: nausea, vomiting, abdominal discomfort, diarrhea, or constipation; in some cases, these side effects can be severe. For patients with diabetes, these medications can also worsen conditions like retinopathy. These medications are contraindicated during pregnancy, in patients with a history of thyroid cancer, pancreatitis, or any known allergy to other GLP-1s.

What Options Are Available and How Effective Are They?

Currently, the FDA has approved three different GLP-1s for the long-term treatment of obesity: Liraglutide (Saxenda®), Semaglutide (Wegovy®), and Tirzepatide (Zepbound®). The latter is a formulation of two different incretins: a GLP-1 and another type called GIP (gastric inhibitory peptide). Research studies have shown that these GLP-1 medications are superior to other long-term FDA-approved anti-obesity medications like orlistat (Xenical®, Alli®), phentermine-topiramate (Qsymia®), and bupropion-naltrexone (Contrave®), leading to almost 20% loss of initial body weight. Moreover, studies have shown that besides aiding in weight loss and blood sugar control, some GLP-1 medications also improve conditions like osteoarthritis, heart failure, fatty liver, and reduce the risk of major adverse cardiovascular events (such as cardiovascular death, heart attacks, and stroke). It is important to note, that while the formulation is similar in medications like Victoza® and Saxenda® (Liraglutide), Ozempic® and Wegovy® (Semaglutide), Mounjaro® and Zepbound® (Tirzepatide), one is the version for diabetes and the other one is the version for weight loss.

How to Take These Medications

Before we move on, it’s important to clarify that it’s strongly recommended that these and any other medications be paired with a healthy diet and regular physical activity to maximize their weight loss effects and benefits. As mentioned earlier, naturally, these incretin hormones act for only a few minutes before they are broken down and inactivated in the human body. The great benefit of these “analogues” is that they are resistant to this inactivation and can last hours to days, which is why some versions, like Wegovy® and Zepbound®, are administered weekly, while Saxenda® is administered daily. This makes them more convenient for patients. The relative downside is that they only come in an injectable pen version, but the good news is that the needle is very short (less than half a centimeter) and almost as thin as a human hair, making the injection nearly painless and user-friendly. These medications come in different strengths, and they require careful monthly dose adjustments by your doctor to find the right dose for you. Importantly, these medications should not be combined with other weight loss medications, as we don’t yet know if this is safe.

Important Facts

Before we finish this post, I want to emphasize a few things. First, it is exciting that we’re experiencing a revolution in obesity treatment, with more medications to come and health policies changing to benefit patients. However, the popularity of these and other medications should not make you forget that these are still medications. While there is a lot of information available, there is also a lot of misinformation about what they are, who should take them, and their risks (among other things). You should always consult with your primary care doctor, endocrinologist, gastroenterologist, or obesity medicine expert. The prescription of these medications requires training, and while there are some options online and on social media that offer these and other medications, you should consult with a doctor as misuse can damage your health. Lastly, obesity is a disease, and its treatment requires a comprehensive approach. These and other medications should not be viewed as quick fixes or miracle solutions, but as useful tools to help you achieve your goals and become healthier.

If you’re considering a medication to help with weight loss, schedule an appointment with your doctor to discuss which option might be best for you.

References:

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