Over the last few years, glucagon-like peptide-1 receptor agonists (GLP-1s) —a class of drugs like semaglutide, liraglutide, and tirzepatide, also known by brand names like Ozempic, Victoza, and Mounjaro—have taken the world by storm.
Sought for their seemingly miraculous ability to help people lose weight, a recent health poll from KFF reports that 6% of Americans are currently on GLP-1s. But, while GLP-1s have helped many people achieve their goal weight, these powerful drugs are not always used in ways that promote long-term weight loss and optimal health overall.
“GLP-1s are revolutionary for a lot of reasons, particularly that it solves a massive problem in our country, but there’s a double-edged sword to them…People do have side effects,” said James LaValle, RPH, CCN, MT, DHM, DHPH internationally recognized clinical pharmacist, author, board-certified clinical nutritionist, told Dr. Terri DeNeui, DNP, APRN, ACNP-BC and founder of EVEXIAS Health Solutions during episode 4 of her podcast, The Dr. Terri Show.
If you’re curious to try GLP-1s or already on them, here’s a handy guide covering what these drugs are, how best to use them, what to expect during your treatment, and safety concerns to keep in mind as you pursue treatment.
What are GLP-1s and How do They Work?
In 1986, scientists discovered that GLP-1 receptor agonists help type II diabetics lower blood sugar levels and manage their metabolism. The first GLP-1 agonist drug developed with this objective, Exenatide, was approved by the FDA in 2005. In the years following Exenatide’s approval, scientists noted GLP-1 agonists also had weight loss benefits for obese patients. In 2014, liraglutide (brand name Saxenda) became the first FDA-approved GLP-1 for weight loss in patients without diabetes.
But How Exactly do GLP-1 Agonists Help People Lose Weight?
“What you’re doing [with GLP-1s] is you’re trying to get your insulin and glucose to appropriately function. The more stress you get under, the more that you eat poorly and drive insulin, which is a stressor, [and] you end up triggering your body’s signal to store fat,” said LaValle. “And what happens is, is that you can diet and exercise. Once you get through a certain turning point with it, you don’t lose weight.”
This is where GLP-1s can come in. GLP-1 receptor agonists have a powerful effect on metabolism because they mimic the action of a hormone naturally made by the body called GLP-1, which is excreted by the stomach after a meal to signal fullness to the brain.
“In comes the GLP-1 agonist, which was originally developed for diabetes, and then we found out that, oh my gosh, people lose weight on these. This is great,” said LaValle.
Studies show that GLP-1 receptor agonists help patients to lose weight — in some cases 20% of their body fat —by decreasing the amount of sugar produced by the liver, slowing digestion, and suppressing appetite.
Beyond their benefits for insulin levels and weight loss, GLP-1s can positively influence glucose levels. High glucose has been linked to a whole host of issues beyond diabetes and weight, it also influences our nervous and digestive systems.
“GLP-1 helps the nervous system. It helps the gut microbiome. It protects your brain from what’s called microglial cell activation…what that means is your brain is on fire, you’re destroying your neurons, leading you to dementia and Alzheimer’s,” said LaValle.
What is the Best Way to Use GLP-1s for Weight Loss?
The most important thing to remember about GLP-1s for weight loss is that they lead to the best results when patients utilize them as part of an overarching strategy that includes adjustment to diet and lifestyle, not as the only strategy.
In other words, GLP-1s are not a band-aid solution to obesity. To lose weight and keep it off, it’s imperative that GLP-1 patients adjust elements of their diet and lifestyle that led to weight gain in the first place.
Dr. Terri has had a patient on semaglutide for 2 years now, and while he initially lost a ton of weight, his progress recently stagnated because he hadn’t made enough changes to his lifestyle, and primarily, he was still eating too much.
“You can eat through the appetite suppressant,” she said.
Likewise, GLP-1s should be regarded with a lot of respect. These are powerful drugs. As Dr. Terri mentions during this podcast episode, the best strategy for dosing GLP-1s, and for preventing negative side effects, is low and slow.
“One of the problems that also occurs is when it’s conventionally prescribed, they start at too big a dose…which creates the side effects, right? I’m too nauseous, I’m constipated, I’ve got diarrhea, I develop, and you know, elevated enzymes,” said LaValle. “There’s a lot of people, they don’t know. They don’t understand that you start low, right. And you build to the minimum effective dose where you start seeing weight loss and stay there.”
What Can You Expect From GLP-1 Treatment?
If you’re interested in GLP-1s, it’s best to meet with your doctor to discuss allergies, pregnancy, age, and drug interactions and to have your labs done beforehand to make sure you are a good fit for treatment. If this looks good, you’ll be prescribed a specific GLP-1 dose, which is administered by self-injection into the skin of your stomach, thighs, or upper arm.
As you begin your GLP-1 treatment, you may experience digestive upset, including mild to moderate constipation, diarrhea, vomiting, and stomach pain. These side effects should wane after the first few weeks, but if they persist, contact your provider and they can help adjust your dose and make you more comfortable.
From there, weight loss occurs gradually over time, sometimes over as long as a year. According to a recent study, patients on GLP-1 drugs should “complete at least 12 weeks of continuous treatment to be able to achieve clinically meaningful weight loss that will positively impact their health.”
Safety Concerns
In some rare cases, more severe and long-term side effects can arise including diabetic retinopathy, gallbladder disease, thyroid cancer, and pancreatitis. But the risk of severe side effects can be mitigated by getting your GLP-1 by prescription from a reputable source, and by having a qualified and knowledgeable provider oversee your treatment.
As DeNeui shared during this podcast episode: “A young man, father of four… got put on GLP-1s by his primary care practitioner and developed acute pancreatitis that got missed because he didn’t get instruction to report abdominal pain. He just thought it was a normal side effect and he ended up in the hospital and died… there are so many clinicians prescribing it that don’t understand there’s a dangerous side, there’s things you got to monitor, there’s questions you need to ask.”
Unfortunately, significant numbers of patients are obtaining the drugs on the internet without a prescription and self-administering without the oversight of a provider—putting themselves at risk for the negative outcomes this young father of four experienced.
In fact, according to a study published by JAMA Network Open in August, about 42% of online pharmacies that sell semaglutide, the generic form of Ozempic, Wegovy, and Rybelsus, “are illegal, operating without a valid license and selling medications without prescriptions.”
As LaValle stresses, getting your GLP-1s this way versus by prescription from a qualified provider, can be a matter of life or death.
“Please do not go online and buy yourself and buy not-for-human use, not-for-animal use products that are injectable…and do not do that without having a proper lab test to make sure it’s safe for you,” emphasized LaValle.
In the end, GLP-1s can help overweight and obese patients shed those unwanted pounds and improve their health, but they are also powerful drugs that should be treated with respect.
For best results, source GLP-1s from a reputable source, take GLP-1s as prescribed by a licensed and qualified provider, and check your mindset: GLP-1s are not the end-all be all for weight loss, but a temporary tool to be used in conjunction with healthy diet and lifestyle changes that will help you sustain your optimal weight indefinitely.