Long-Term Safety of GLP-1s vs Risks Of Untreated Obesity

Are GLP-1 medications safe long term—or are we reacting to headlines and bias? We open with a clear, step-by-step look at how drugs reach the market, from discovery through Phase 4 surveillance, to ground our conversation in facts rather than fear. With two decades of real-world use behind GLP-1s, we unpack what the data actually show: common GI side effects that are usually manageable, rare contraindications tied to medullary thyroid cancer families, and concerns like pancreatitis that haven’t held up as causal signals.

From there, we zoom out to the comparison that matters most: the risks of treatment versus the risks of doing nothing. Untreated obesity drives type 2 diabetes, high blood pressure, stroke, heart failure, kidney disease, fatty liver advancing to cirrhosis, sleep apnea, blood clots, osteoarthritis, and higher rates of several cancers. When you weigh decades of harm against the well-characterized profile of GLP-1s, the balance tips toward treatment—especially as evidence grows for benefits beyond weight, including cardiovascular protection, liver health, kidney outcomes, and sleep apnea improvements.

We also tackle the social friction around these medications: the idea that weight loss should be “earned” through struggle. Obesity is not a willpower problem; it’s a complex, biological disease shaped by hormones, neurocircuitry, genetics, and environment. GLP-1s help correct those pathways, enabling meaningful, sustained loss for people who’ve tried everything. Even if it feels “easier,” the true measure is better health and longer lives. If you’re wrestling with concerns, we invite you to reflect on the evidence, examine weight bias, and join a conversation rooted in science, empathy, and outcomes.

If this episode helped you think differently, share it with someone you care about, subscribe, and leave a review so more listeners can find evidence-based metabolic health. Your feedback guides future topics and keeps the conversation moving forward.

Podcast Mentioned: How to manage side effects of GLP-1 agonists

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Transcript

Welcome And Focus On Metabolic Health

Dr. Lindsay Ogle 0:01

Welcome to the Modern Metabolic Health Podcast with your host, Dr. Lindsay Olde, board certified family medicine and obesity medicine physician. Here we learn how we can treat and prevent modern metabolic conditions such as diabetes, PCOS, fatty liver disease, metabolic syndrome, sleep apnea, and more. We focus on optimizing lifestyle while utilizing safe and effective medical treatment. Please remember that while I am a physician, I am not your physician. Everything discussed here is provided as general medical knowledge and not direct medical advice. Please talk to your doctor about what is best for you. What's a safety long term? I would love to take the time with you guys and talk about this concern that I just hear so commonly in comments on social media or in conversations with people both in and outside of the medical community about the treatment of obesity with our new and effective medications, specifically our GLP1 agonists. What's a safety long term? This concern I think comes from a combination of two places, and for some people it's heavily one or the other, and for others, it's truly a mixture of both. And some of that may be upfront and obvious, and some of it may be subconscious, coming from a true place of concern and also a place of weight biased. And I'm gonna address both of these. The place of concern is just genuine concern for either themselves or people they know that are on these medications or just the health of society in general. With any new medication, there are years and years and years of development behind the scenes. First, it starts with discovery and development. This is just where the scientific researchers are looking into what's available and discovering new molecules and different combinations and compounds that may be eventually a treatment option for us in the future. Then there's pre-clinical research that's done. This is what's done in the lab to prove their theory that this molecule or compound will be effective or may be effective in animals and in humans. Once that theory is proven to be a true possibility, then we move towards clinical trials. And there are four phases of clinical trials that are set out to protect the general public. The first is to ensure safety and to determine an appropriate dosage. And so this is a very small trial. People who have given their consent to take the medication, take the medication, and report any set side effects or adverse events. And they compare that to a placebo medication. So half of the people are taking what they think is the medication, but truly there's no active ingredient in that treatment, and then half are getting the actual medication that is being studied, and then they report the response to the medications, and that is compared. In this first trial or this first phase, we are looking to make sure that it is safe and nobody is having dangerous side effects at that point. Phase two is when we get a bigger group of people and we do the same thing. Now we're still gonna monitor for side effects and report those and keep track of what is people are experiencing in a negative way with the medication, but we're also looking at the effectiveness, and that's the goal of phase two. Is this medication truly causing the change that we're looking for it to change? Is it really helping people? Phase three confirms what phase one and two have demonstrated, and this needs to be better than what the current treatment is already on the market. So, for consideration, um, the GLP one agonist, we want to make sure that it's more effective than pentermine has been or metformin has been for diabetes. Um again, we're constantly looking and getting feedback about side effects here and how effective the medication is. And then phase four is really where we're getting even more long-term data. This is when the medication has gone to market and the entire population has access to this medication. It does not mean insurance will cover it, but it is available to be prescribed by your doctor and sent and picked up at the pharmacy. And side effects are being monitored and reported during this time. So, this is how any medication for any condition in the United States is brought to market. And again, there are those several phases that the medication has to go through to prove that it is first safe, second effective, third more effective than what is currently on the market, and then we're going to use it and monitor it continuously while it's on the market. We have all seen when something is on the market and has been proven to be dangerous, maybe it didn't get picked up because it's so rare, the complication that in the trials it didn't happen or it took an extended period of time for that to develop, then it's noted and removed from production and availability to the public. Now, this is really key because GLP1 agonists have been on the market in the US since 2004. They have been, at the time of this recording, out for 21 years. So we have over two decades of data, and after 20 years of using GLP1 agonists, what we know is that by far the most common side effect is stomach upset and GI symptoms. We're talking about nausea, acid reflux, constipation, diarrhea. And a lot of that can be managed, and I did a whole video about how to manage the side effects of a GLP1 that I'll link here for you to take a look at and to troubleshoot if you're having any of these issues. But most people, the vast majority of people, don't have any side effects on the medication when they're prescribed appropriately. Some of the more significant issues that we see are really more related to just weight loss in general. Development of gallstones is one of those. There are studies on lab rats that have shown an increased risk of medullary thyroid cancer, medullary only, so not other types of thyroid cancer. So, but this has not been proven in human studies. We are cautious and we do not prescribe these medications for anyone with a family history of medullary thyroid cancer or a rare condition called MEN. And if that is in your family history, it's better safe than sorry, do not take these medications. But otherwise, if you have hypothyroidism, hyperthyroidism in your family, or a personal history, you can still safely take these medications. There are concerns about pancreatitis that have not really panned out to be actual side effects from these medications. So I'd like to take all that information and summarize it by saying one, that medications are very well studied and have to meet vigorous standards before they're approved for the general pop population. And even when they are, they are constantly being monitored for safety and will be removed if they are found to be unsafe. And then, two, the common side effects are very mild and not life-threatening. Now I want to highlight that because we are comparing this to what happens if we do not treat the disease of obesity. If we do not treat the disease of obesity for years and decades, we know that it is very, very likely that they are going to have complications from that excess weight. The complications that we see, I can't even name them all in one video, but some of the most common ones are type 2 diabetes, high blood pressure, abnormal cholesterol levels, cardiovascular disease, including heart attack, heart failure, stroke, chronic kidney disease, fatty liver disease, which can lead to cirrhosis and liver failure, obstructive sleep apnea, increased risk for blood clots in the legs and in the lungs, dementia, osteoarthritis, and need for knee replacements, hip replacements, several cancers, including breast, colon, esophageal, uterine, and others. Skin infections and conditions like hydradenitis operativa and candidyl or yeast infections. Again, there are others, but those are some very common ones that can be serious enough to cause death or significant morbidity or affect our quality of life. When you compare these two, I would go with treating the obesity with this medication that over 20 years we have seen it is safe. Not only is it safe, they are highly effective and are now being proven to treat and prevent conditions such as cardiovascular disease, fatty liver disease, chronic kidney disease, obstructive sleep apnea, and I'm sure we are going to find more and more and more. We've seen benefits in people who drink excessive amounts of alcohol or use other drugs. These medications we are going to just continue to see benefits and indications for their use. Going back to the initial two reasons why I think people bring up this concern are the people that are concerned about the true safety of themselves and people they love. And I think we address that pretty well. But then there are the other people that have the weight bias. And I think that this comes from people who don't want it to be easy for people to lose weight. Like I said, these medications are highly effective. For semaglutide, we go via the brand name for treating obesity, and on average, people lose 15% of their body weight. For trazepitide, or the brand name Zeppound, people lose 20% of their body weight. And of course, this varies. Some people it's less, some people it's even more. But people who have not been able to lose weight for years and decades now are able to take this medication and be successful. And in all honesty, many people don't want to see it easy. They have an issue with that. I want those people to ask themselves why. Why can't it be easy? As we grow as humans, as we evolve, everything in our life becomes easier. No longer do we walk or bike or take a horse to visit family members who live in towns far away or states across the US. We drive or take a train or a bus or a plane. And nobody thinks twice about somebody who buys a plane ticket from Florida to California. We wouldn't say, oh, you're taking the easy way out. You should ride your bike there. That would be ridiculous. It's a similar thing with these medications. We constantly are becoming more efficient. And we never shame other people for using things that are more efficient. But we do it for things that we think people should suffer through. And having excess weight is one of those things that as a society we think people should suffer for. And I think that this is incredibly unfortunate. It's a complete lack of understanding of what is actually happening in the body. Oftentimes, this is coming from people who have never struggled with their weight before. They think that if somebody would eat just like them, then they wouldn't have this issue. But that is not the case. I will have to have another video that goes into all of the reasons why that is not the case. Going into the true biological changes that happen when someone is carrying excess body fat. We have proven this. And these medications help address that. So while I don't personally think it's taking the easy way out, I do not see it that way. I see it as treating the underlying biological changes that have led to the excess weight gain and that prevent weight loss from occurring even when somebody is eating nutritiously and exercising. These medications treat those underlying causes and finally allow the body to release the excess weight. But even if it was the easy way out, so what? I encourage it, especially because we know these medications are safe. If you are one of those people and you are worried about these medications and worried about so many people taking them, just take a second to really reflect on why you are concerned. And if so many scientists, doctors, researchers have worked with patients who are taking these medications, have studied them, have lived this experience, and have seen the amazing results that are happening. The true reversal of chronic conditions like diabetes, fatty liver disease, obstructive sleep apnea, less joint pain, more energy, and so much more. Why would you shame anybody from using that? I encourage a discussion, so if you have thoughts, please let me know. You can visit my website, Missouri Metabolic Health, send me a comment directly there. I'd be happy to address it. And I hope we continue this conversation and learn more over time because I know a lot more research is coming out, more treatment options are coming out, and I can't wait to talk those, talk about those more with you in the future. Thank you for listening and learning how you can improve your metabolic health in this modern world. If you found this information helpful, please share with a friend, family member, or colleague. We need to do all we can to combat the dangerous misinformation that is out there. Please subscribe and write a review. This will help others find the podcast so they may also improve their metabolic health. I look forward to our conversation next week.