Understanding the Basic Science: What Are GLP-1 Medications?

Before we can evaluate whether GLP-1 drugs are right for anyone, we need to understand what GLP-1 actually is and how these medications work in your body. GLP-1 stands for glucagon-like peptide-1, and it’s a hormone that your small intestine naturally produces when you eat. Think of GLP-1 as your body’s sophisticated meal management system, coordinating multiple responses to ensure your body processes food efficiently and maintains stable blood sugar levels.

When food hits your intestines, they release this hormone to coordinate several important responses throughout your body. First, GLP-1 tells your pancreas to release insulin, but here’s the brilliant part: it only does this when your blood sugar is elevated. This is fundamentally different from some older diabetes medications that can cause dangerous low blood sugar episodes. The GLP-1 system is smart enough to provide help only when you actually need it, managing blood sugar without creating the risk of hypoglycemia.

Second, GLP-1 blocks the release of glucagon, which is another hormone that raises blood sugar. This creates a double benefit for blood sugar control, working from both directions simultaneously to keep glucose levels stable. Third, and this is where things get particularly interesting from a weight loss perspective, GLP-1 slows down how quickly your stomach empties. Food moves through your digestive system more slowly, which helps prevent blood sugar spikes and creates a prolonged feeling of fullness that can dramatically reduce appetite.

Fourth, GLP-1 acts directly on your brain, specifically targeting areas that control hunger and satiation. It’s literally communicating with your brain’s appetite centers to signal that you’ve had enough food and can stop eating. This isn’t willpower or discipline. It’s a biological signal that fundamentally changes how hungry you feel and how satisfied you are with smaller portions.

Here’s the challenge that scientists faced when trying to harness this system therapeutically. Natural GLP-1 in your body breaks down extremely quickly, with an estimated half-life of just a couple of minutes. You can’t simply inject natural GLP-1 as a medication because it wouldn’t last long enough to produce meaningful effects. The breakthrough came when researchers figured out how to create synthetic versions that last much longer in your body. The first GLP-1 agonist received FDA approval back in 2005, but these medications really exploded in popularity over the past few years as newer, more effective versions became available.

The Current Landscape of GLP-1 Medications

Today’s GLP-1 medication market includes several different options with varying dosing schedules and approved uses. Some require daily injections while others work with weekly administration. Some are specifically approved for diabetes management, others for weight loss, and some carry approvals for both indications.

The brand names you’re probably most familiar with are Ozempic and Wegovy, both of which contain the active ingredient semaglutide. There’s also Zepbound, which contains tirzepatide, along with several other options on the market. Something crucial to understand is that while tirzepatide medications like Zepbound are often grouped with GLP-1 drugs, they’re actually what researchers call dual agonists. Tirzepatide activates both GLP-1 receptors and GIP receptors, which may explain why it often shows even more dramatic effects in clinical trials.

The Remarkable Benefits Beyond Weight Loss

When most people think about GLP-1 drugs, weight loss immediately comes to mind. The weight loss effects are genuinely impressive, but what’s emerging from the latest research is that these medications provide a range of health benefits that extend far beyond what anyone initially expected from simple weight reduction.

Let’s start with what we know best: the weight loss results. In clinical trials, people taking Wegovy typically lose an average of 12 to 15% of their body weight over 68 weeks. For tirzepatide medications like Zepbound, the numbers climb even higher, with up to 22% body weight loss demonstrated in trials. To put this in real-world terms, we’re talking about a 200-pound individual losing 25 to 45 pounds. These are numbers we historically only saw with bariatric surgery or with extraordinarily dedicated work on diet, nutrition, exercise, sleep, stress management, and sometimes hormone optimization. The newer medications in development, like retatrutide (a triple agonist), are showing even more dramatic results in early trials, with up to 24% weight loss reported.

What’s really exciting researchers from a medical perspective is the cardiovascular benefits that appear to be independent of weight loss itself. The SELECT trial, which studied people with obesity and established heart disease, found that semaglutide reduced the risk of major cardiovascular events including heart attacks, strokes, and cardiovascular death by 20 to 25%. These benefits were so significant that the FDA approved Wegovy specifically for reducing cardiovascular risk in this population, not just for weight loss. What’s remarkable is that these cardiovascular benefits appear regardless of how much weight people actually lose, suggesting that the medications are doing something directly beneficial for heart health beyond the weight loss effect.

For people with type 2 diabetes, GLP-1 drugs excel at their original intended purpose. They lower A1C (the key measure of blood sugar control) by one to two percentage points, which is clinically very significant. Unlike some other diabetes medications, GLP-1 drugs don’t cause hypoglycemia when used alone or with metformin, which represents a major safety advantage for the diabetic population.

In January 2025, the FDA approved semaglutide specifically for protecting kidney function in people with diabetes and chronic kidney disease, making it the first GLP-1 drug approved specifically for kidney protection. Research shows these medications can slow the progression of kidney disease and reduce the risk of kidney failure, meaning we’re talking about protective effects across multiple major organ systems.

Perhaps most surprising are the emerging benefits for brain health and mental health conditions. A comprehensive study published in Nature Medicine in early 2025 looked at 175 different health outcomes in over 200,000 people taking GLP-1 medications. The findings were striking: reduced risk of seizures and epilepsy, reduced risk of addiction to alcohol, opioids, cannabis, and other stimulants, reduced suicidal thoughts and self-harm behaviors, reduced eating disorders like bulimia, reduced psychotic disorders including schizophrenia, and reduced neurocognitive disorders like Alzheimer’s and dementia.

Researchers believe this happens because GLP-1 receptors exist throughout the brain, particularly in areas involved in impulse control, reward processing, and addiction. These medications may literally be helping to rewire how our brains respond to various substances and behaviors. In 2024, tirzepatide received approval for treating moderate to severe sleep apnea in obese adults, with the medication significantly reducing sleep apnea episodes. For those familiar with the strength training and powerlifting world, sleep apnea is prevalent among heavier individuals, whether from body fat, muscle mass, or neck circumference from developed trap muscles. Addressing sleep apnea immediately helps not only recovery but also impacts hormone regulation, weight management, energy levels, and overall health.

The research also demonstrates benefits for metabolic liver disease, also called fatty liver disease. The medications appear to help reduce liver fat and inflammation, potentially slowing progression to more serious liver problems. We’re talking about a medication that addresses multiple major health issues simultaneously, which could genuinely improve quality of life when these conditions are managed appropriately.

However, it’s important to put these benefits into proper perspective. While the range of benefits is impressive, most individual benefits represent approximately 10 to 20% reduction in risk. That’s meaningful, especially for conditions where we don’t have many effective treatments, but it’s not a cure-all. As one researcher put it, these medications may be most beneficial when combined with other interventions like lifestyle changes and additional treatments, rather than serving as standalone solutions.

The Challenges: Why Do So Many People Stop Taking GLP-1 Medications?

If GLP-1 drugs were perfect medications, we wouldn’t see 50 to 65% of people discontinuing them within a year. Those statistics should make us pause and ask what’s driving these remarkably high discontinuation rates. What risks should people be aware of, and what challenges do real users face?

According to 2024 and 2025 studies, between 46.5 and 64.8% of people stop taking GLP-1 medications within the first year. For people without diabetes, the discontinuation rate climbs even higher than for those managing diabetes. Research from Northwestern Medicine called these “staggeringly high discontinuation rates” that should “raise alarms for clinicians and policymakers.” So what’s actually happening here?

The most common reason people stop GLP-1 medications is gastrointestinal side effects. Nausea, vomiting, diarrhea, and constipation aren’t rare occurrences. They affect 40 to 70% of people taking GLP-1 drugs, depending on which specific medication they’re using. In a 2025 survey of patients who discontinued GLP-1 medications, 64% said the drugs “made me feel sick” and 45% reported they “made me throw up.”

From personal conversations with people who have tried these medications, all three individuals I’ve spoken with voiced these exact concerns. They described feeling nauseous to the point where it was hard to enjoy their day, or experiencing vomiting and diarrhea that made the medication feel worse than their original health concerns. All three have since discontinued their medications. While my sample size is small, it aligns perfectly with what the broader research shows.

These side effects are often most severe when starting the medication or increasing the dosage. The good news is that for many people, these symptoms improve over time as the body adjusts. This pattern isn’t unusual for medications, where initial side effects tend to be the worst. The medications are typically started at low doses and gradually increased to help minimize these problems, but for some people, the side effects remain intolerable even at therapeutic doses.

The situation creates a genuine dilemma. If you’re already struggling with your health, body composition, and daily functioning, adding severe nausea, vomiting, or diarrhea into the equation can feel counterproductive. You’re theoretically taking a medication to improve your health, yet you feel significantly worse. It’s completely understandable why this drives people to discontinue treatment.

Another widely discussed issue is what’s been termed “Ozempic face.” This refers to facial changes that happen with rapid weight loss, primarily loss of facial fat that can make people look older or give their face a sunken appearance. It’s important to understand this isn’t specific to GLP-1 drugs. It can happen with any rapid weight loss. When you lose weight quickly, your body doesn’t have time to gradually adapt. The faster the weight loss, the more noticeable these changes become. For people losing 100 to 150 pounds or more, this can become significant enough that some are even considering facial cosmetic procedures, though whether this represents actual need or body dysmorphia driven by societal pressure is worth considering.

We also need to discuss more serious potential risks, though they’re rare. Pancreatitis, or inflammation of the pancreas, has been reported with GLP-1 medications, though multiple large studies haven’t established a clear causal relationship. People with diabetes and obesity already have higher baseline risk of pancreatitis, making it difficult to determine if the medications are actually causing the problem or if it’s coincidental.

Gastroparesis, a condition where the stomach empties very slowly or stops emptying altogether, represents a more serious concern than the normal digestive slowing the medications cause. While rare, it can require stopping the medication and medical intervention. There have also been reports of acute kidney injury, primarily due to severe dehydration from nausea and vomiting. This underscores the critical importance of staying well hydrated and seeking medical attention if side effects become severe.

The Financial Reality and Supply Chain Issues

Cost represents another major barrier. These medications can cost $1,000 or more per month without insurance coverage, and even with insurance, co-pays can be substantial. Research shows that people paying more than $60 per month have significantly higher discontinuation rates than those with lower costs. Interestingly, those paying over $100 per month sometimes stick with treatment longer, potentially because the psychological investment keeps them committed. This mirrors what we see in business: inexpensive services often see high turnover because people aren’t truly invested, while higher-priced services tend to see better retention because people value what they’re paying for.

Insurance coverage varies dramatically. Many plans cover GLP-1 medications for diabetes but not for weight loss, even though they’re often the same drugs at different doses. This creates a frustrating situation where someone 30 pounds overweight without diabetes might not get coverage, even though achieving weight loss could prevent future diabetes and cardiovascular disease. Whether these medications should be classified as preventative or reactive healthcare remains a genuinely sticky subject, as they’re being given to people who could have potentially prevented their current situation earlier, yet they’re also preventing more serious future complications.

Medication shortages have also been a real problem, especially in 2023 and 2024. When people can’t consistently access their medication, they’re far more likely to discontinue treatment entirely. The data shows clear spikes in discontinuation rates during periods of supply shortages, which makes perfect sense. With more manufacturers entering the market in 2025, access has likely improved, but the early supply constraints definitely contributed to the high discontinuation rates.

The Weight Regain Problem and Long-Term Commitment

One particularly interesting finding is that many people discontinue GLP-1 medications after reaching their weight loss goals, treating them more like a temporary intervention rather than long-term treatment. This creates a significant challenge because weight regain is common after stopping GLP-1 medications. The drugs don’t permanently reset your metabolism or appetite regulation. When you stop, many of the biological drives toward weight regain return.

This is where I want to be very clear about my perspective. I’m not against GLP-1 medications, especially if they get people moving in the right direction toward better health. If these drugs decrease diabetes risk, improve cardiovascular health, provide brain health benefits, and protect kidney function, those are genuinely amazing outcomes that can dramatically improve quality of life. However, there’s a critical question everyone needs to answer: if this is the only intervention you’re going to take, is it an intervention you’re willing to maintain for the rest of your life?

If you stop taking GLP-1 medication and nothing else has changed—you haven’t worked on nutritional habits, physical activity, sleep quality, hydration, or stress management—your success will be significantly limited compared to those making lifestyle changes alongside the medication. Remember our discussion about the 75 Hard program in a previous episode: the value wasn’t primarily about weight loss but about the psychological transformation that then supports sustainable weight loss. The same principle applies here.

If you’re interested in GLP-1 medications for yourself or someone you know, the weight loss benefit is certainly worth celebrating and supporting. But we should simultaneously work on improving lifestyle factors. That’s where the real long-term success comes from.

Who Should Consider GLP-1 Medications?

Based on current research and FDA approvals, several groups show the strongest evidence of benefit. For people with type 2 diabetes, particularly those who need better blood sugar control and could also benefit from weight loss, GLP-1 medications are often an excellent choice. The cardiovascular and kidney protection benefits provide significant additional advantages beyond glucose management. While I still believe people should improve physical activity and nutrition habits, these individuals clearly have type 2 diabetes that needs to be addressed, and GLP-1s can help move them away from this lifestyle-driven condition.

People with obesity and cardiovascular disease represent another clear candidate group. The SELECT trial specifically studied this population and found dramatic reductions in heart attacks, strokes, and cardiovascular deaths. For someone with obesity and established heart disease, the cardiovascular benefits alone likely justify treatment, potentially extending both quality and length of life.

People with obesity and multiple health conditions like high blood pressure, sleep apnea, fatty liver disease, or prediabetes may benefit from GLP-1 medications addressing multiple problems simultaneously, making them strong candidates for this treatment approach.

There are also emerging candidate groups where the evidence is still developing but shows promise. People with addiction issues represent one such group. The research on reduced addiction behaviors is compelling but relatively new, and it’s not yet an approved use. However, it’s an area of active investigation that could prove beneficial in coming years, especially for those addicted to harmful substances or even food itself.

People at risk for dementia represent another emerging category. The cognitive protection findings are interesting, but we need longer-term studies to understand if medications truly prevent or delay neurodegenerative diseases. Having watched a loved one pass away from dementia, I completely understand why this would be worth considering, especially in older populations if clear benefits emerge.

Important Considerations Before Starting GLP-1 Medications

If you or someone you know is considering GLP-1 medications, several important factors deserve careful thought. First, consider your weight loss goals and expectations. These medications work best for people who need to lose significant amounts of weight, typically those with obesity (BMI over 30) or those who are overweight (BMI 27-28) with existing health conditions. If you only need to lose 10 to 15 pounds, the risk-benefit calculation is different. While I won’t claim 10 to 15 pounds is always easy to lose, it’s generally much more manageable through quality exercise and nutrition interventions alone.

Commitment to long-term treatment is essential. The evidence suggests these work best as long-term medications, not one or two month interventions. If you’re looking for a short-term solution, GLP-1s probably aren’t right for you. Consider whether you’re willing to commit to at least 6 to 12 months minimum. If you’re not willing to maintain treatment that long, you might want to wait or explore other alternatives until you’re ready for that longer commitment.

Financial considerations matter significantly. Can you afford these medications long term? Discontinuing purely due to cost will likely lead to weight regain if you’re taking them for weight loss. It’s genuinely frustrating that in today’s healthcare system, beneficial medications are often financially out of reach. I believe preventative healthcare should be much more affordable and rewarded, though whether GLP-1s qualify as truly preventative when they’re being given to people who are already in poor enough health to need them is admittedly debatable.

Tolerance for side effects is another key factor. Can you handle potential gastrointestinal issues for the first two to three months, maybe even longer? Being educated about realistic expectations can help prepare people mentally for what’s coming, which may improve their ability to persist through the adjustment period.

Who Should Be Cautious About GLP-1 Medications

Certain groups should approach GLP-1 medications with extra caution. People with a history of pancreatitis should know that while causation hasn’t been definitively proven, many doctors are cautious about prescribing GLP-1s if there’s pancreatitis history. People with gastroparesis or a history of severe digestive issues should also be careful, as these medications slow stomach emptying and could worsen existing problems.

People planning surgery need to know that GLP-1 medications must be stopped before procedures requiring anesthesia because they slow digestion and increase aspiration risk. This is particularly important for those considering weight loss surgery while on GLP-1s, as you’d need to discontinue the medication before the procedure.

The Critical Importance of Specialist Care

Recent research shows that people who receive GLP-1 prescriptions from doctors specializing in obesity medicine or endocrinology are more likely to stay on treatment successfully than those prescribed by other specialists. This makes perfect sense for several reasons. Specialists are more likely to set appropriate expectations about side effects, use proper dose escalation strategies, provide ongoing support for side effect management, and understand when these medications are and aren’t appropriate.

A good specialist will educate you on all available options, not just sign off on whatever you request. If a doctor immediately prescribes something without discussing alternatives, that’s a red flag. You should be able to make an informed decision based on a comprehensive understanding of your options. This isn’t about them making money from prescriptions; it’s about genuinely serving your health and wellness needs.

The Role of Lifestyle Changes: The Critical Missing Piece

These medications work best when combined with lifestyle modifications. This isn’t negotiable or optional for optimal results. GLP-1 drugs aren’t replacements for healthy eating and physical activity. They’re tools that make these changes easier to implement and maintain, giving you momentum to build on.

Think of it this way: if you take the medication and lose 10 to 15 pounds in the first month or two, that’s genuine motivation. You’re seeing real results. If you then start eating slightly better, sleeping more consistently, going to the gym twice a week, taking a walk one day a week, you’re doing things that promote long-term health on top of the medication’s effects. That’s the major win we should be aiming for.

I view GLP-1 medications as providing biological assistance for behavior changes that might otherwise be very difficult to sustain long term. This is your assistant helping keep the needle moving forward. It’s not an excuse but an aid in your process. This is admittedly an overexaggeration, but it’s somewhat similar to creatine supplementation. Creatine assists muscle growth, power production, and athletic performance, but you’re not relying solely on creatine to carry the weight of your training. GLP-1 medications are clearly more powerful with broader health implications, but the principle of viewing them as assistive tools rather than complete solutions remains the same.

Looking to the Future of GLP-1 Medications

The field of GLP-1 and related medications is moving incredibly fast. Development of oral versions is underway, with currently only one oral GLP-1 available. Longer-acting formulations and combination drugs targeting multiple hormone pathways simultaneously are in development. Triple agonists like retatrutide, which activate GLP-1, GIP, and glucagon receptors, are showing even more dramatic weight loss in trials—up to 24% body weight reduction. These could become available within the next few years.

Researchers are also investigating GLP-1 drugs for conditions we haven’t discussed, including Parkinson’s disease, Alzheimer’s disease, peripheral artery disease, and other related conditions. The breadth of potential applications continues to expand as we understand more about where GLP-1 receptors exist in the body and what they do.

Final Thoughts: A Balanced Perspective on GLP-1 Medications

Let me distill what we’ve learned into actionable insights. First, these medications represent a genuine breakthrough in modern medicine. The combination of weight loss, cardiovascular protection, brain health benefits, and potential for fighting addiction makes them unlike anything we’ve seen before. This is as close as we’ve come to a medication that can produce dramatic weight loss with broader health benefits, representing a true win for modern medicine in 2025 and beyond.

Second, they’re not magic bullets. The high discontinuation rates, significant side effects for many people, and cost issues mean they’re not right for everyone. Success requires careful patient selection, appropriate expectations, and long-term commitment. They need to be prescribed to the right people who are making informed decisions with realistic expectations and understanding the long-term commitment required.

Third, the decision should be individualized. Age, health conditions, financial situation, tolerance for side effects, and treatment goals all matter for each person. This isn’t a decision to make based on social media trends or celebrity endorsements. Despite GLP-1 advertisements appearing in virtually every sporting event commercial break, you should make this decision with your healthcare specialist based on your individual circumstances.

Fourth, if you’re considering these medications, work with the right doctor. Find a specialist in obesity medicine or endocrinology who can help you succeed better than doctors who only occasionally prescribe these drugs. When dealing with newer, groundbreaking medications, you want the most educated people in your corner if you’re going to commit to a year or more of treatment. Finding that specialist should be step number one once you’ve decided this medication might be right for you.

Fifth, think long term. This is a long-term treatment medication, not a one, two, or three month stint. If you or someone you know wants to use GLP-1 medications, emphasize the long-term commitment piece. This applies to anything health, fitness, and lifestyle related. There are no quick fixes. There are things that can provide temporary relief and address underlying issues, but most health and fitness interventions require long-term commitment, and GLP-1 medications are no exception.

What we’re actually seeing might be the beginning of a completely new era in medicine, one where we can effectively treat obesity and its related conditions with medications that work with rather than against our natural biology. The discovery that these medications affect brain health, addiction, and multiple organ systems suggests we’re just scratching the surface of GLP-1 potential.

But as with any powerful tool, medications need to be used thoughtfully and appropriately for the right people. GLP-1 medications are neither miracle cures nor dangerous drugs. They’re powerful medications that can provide significant benefits for the right people in the right circumstances. The key is having realistic expectations, understanding the benefits and risks, and making informed decisions based on individual circumstances rather than headlines and social media trends.

As the healthcare field continues to evolve, stay informed through reliable sources and remember that the best treatment decisions are always made in partnership with healthcare providers who understand both the science and your individual needs. Don’t make this decision purely based on social media, celebrities, or TV advertisements. Do your research, consult specialists, and make the choice that’s right for your specific health situation.