GLP-1s aren't cheating. What you are doing during them is what is important.
What these peptides actually do and why lifting is so important.
Let me get this out of the way: I'm not anti-GLP-1. In fact, I am a fan. I believe many people can benefit from them.
Semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) are some of the most effective weight-loss tools medicine has ever produced, in my opinion. If your physician prescribed one and it's working, you didn't take a shortcut.
You're treating a medical condition with a medical tool.
But there are two loud camps right now, and both are wrong. One says these drugs are cheating. The other says the shot is all you need. The research lands somewhere in between.
So, let's go through it: how these drugs actually work, what the clinical trials show, the side effects, and then the part that matters most to me as a personal trainer and coach.
Then I'll explain why lifting is the piece that determines whether this ends well for you.
GLP-1 Is Something Your Body Already Makes
GLP-1 (glucagon-like peptide-1) isn't a lab invention. It's a hormone your gut releases every time you eat. Specialized cells in your intestine sense food coming through and send GLP-1 into your bloodstream to help manage what happens next (1).
The problem is that natural GLP-1 lasts only a couple of minutes before an enzyme breaks it down. The drugs are engineered versions that resist that breakdown, which is why one injection lasts a full week. Same signal, much louder, much longer.
How the Drugs Work: The Three Main Pathways
GLP-1 receptors show up all over the body, but three places drive most of the weight loss (1).
The pancreas. GLP-1 tells your pancreas to release more insulin when blood sugar is elevated, and to release less glucagon, the hormone that raises blood sugar. The key word is when. The effect is glucose-dependent, which is why these drugs lower blood sugar without usually crashing it on their own. This is why they were first developed as diabetes drugs.
The stomach. GLP-1 slows how quickly your stomach empties into your intestine (1). Food sits longer, you feel full longer, and you eat less at the next meal. This is also where a lot of the nausea comes from, which we'll get to.
The brain. This is the big one. GLP-1 receptors in the hypothalamus and brainstem, the regions that regulate hunger and satiety, turn down appetite (1). Patients describe it as the "food noise" going quiet: the constant background thinking about the next snack just stops.
You're not white-knuckling a diet. You're simply less hungry.
The Newer Drugs Hit More Than One Target
Tirzepatide (Mounjaro, Zepbound) is a dual agonist. It activates the GLP-1 receptor, plus the receptor for GIP (glucose-dependent insulinotropic polypeptide), another gut hormone involved in insulin release and fat metabolism (3).
Retatrutide goes one step further. It's a triple agonist that hits GLP-1, GIP, and glucagon receptors (4). Adding glucagon sounds backwards for a weight-loss drug, but glucagon signaling appears to increase energy expenditure and pull fat out of the liver. The combination is designed to reduce intake and increase output.
More targets, more weight loss, as you're about to see.
What the Clinical Trials Actually Show
STEP 1 (semaglutide). Nearly 2,000 adults with obesity took weekly semaglutide or placebo for 68 weeks, alongside lifestyle counseling. The semaglutide group lost 14.9% of body weight on average versus 2.4% with placebo, and half the semaglutide group lost 15% or more (2).
SURMOUNT-1 (tirzepatide). More than 2,500 adults, 72 weeks. At the highest dose, participants lost an average of 20.9% of their body weight versus 3.1% on placebo. Over half of those on the top dose lost 20% or more (3).
That's approaching the results of bariatric surgery.
Retatrutide. In the phase 2 trial, the highest dose produced an average 24.2% weight loss at 48 weeks, versus 2.1% on placebo (4). Eli Lilly has since reported positive phase 3 results and says it plans to file for U.S. approval in early 2027 (5).
Here's the important part: retatrutide is not FDA approved. Anything being sold online as "retatrutide" right now isn't a legitimate prescription product, and you have no way of knowing what's actually in that vial. I am not saying it doesn't work. What I am saying is there is no proof you are getting what you think you are getting.
SELECT (heart outcomes). This is the trial that changed the conversation. More than 17,600 adults with existing heart disease and excess weight, but no diabetes, were followed for over three years. Semaglutide cut the combined risk of heart attack, stroke, and cardiovascular death by about 20% compared with placebo (6). That's not a cosmetic benefit. It's a real reduction in the things that kill people.
So, the drugs work, and in the right patients they do more than move the scale.
Now for the costs.
The Side Effects Nobody Puts on the Billboard
GI problems are common. Nausea, diarrhea, vomiting, and constipation are the most frequent side effects across every trial. In STEP 1, they were mostly mild to moderate and faded with time, but 4.5% of the semaglutide group still quit because of GI side effects, versus 0.8% on placebo (2). In SELECT, where people stayed on the drug for years, 16.6% stopped because of adverse events, roughly double the placebo rate (6). Most of this happens during dose increases, which is why doses are ramped up slowly.
Rare but serious GI events exist. A 2023 study in JAMA compared people using GLP-1s for weight loss with people using a different weight-loss drug. The GLP-1 users had a higher risk of pancreatitis, bowel obstruction, and gastroparesis (stomach paralysis) (7). These events are uncommon, and because it was an observational study, other researchers have questioned how strong the link really is. But they're real enough that you should know the warning signs: severe abdominal pain, persistent vomiting, or being unable to keep food down means you call your doctor.
This is another reason your peptide protocol should be doctor-monitored. Most of the time, they are safe; occasionally they cause issues. A random online site doesn't come with a doctor or their team.
Gallbladder issues. Rapid weight loss of any kind raises the risk of gallstones, and it's a listed risk with these drugs.
Heart rate. These drugs can raise resting heart rate. In the retatrutide trial, heart rate rose in a dose-dependent way, peaked around 24 weeks, and then came back down (4).
Thyroid warning. Semaglutide and tirzepatide carry an FDA boxed warning based on thyroid tumors seen in rodent studies. Whether this applies to humans hasn't been established, but people with a personal or family history of medullary thyroid cancer or MEN2 syndrome aren't supposed to take them.
Surgery and anesthesia. Because these drugs slow stomach emptying, food can still be sitting in your stomach at the time of a procedure. If you're having surgery or sedation, tell your care team you're on one.
None of this means the drugs are dangerous for most people. It means they're real medications with real trade-offs, and those trade-offs belong in a conversation with your prescriber.
There's one side effect that barely gets mentioned in the doctor's office, and it's the one I care about most.
The Side Effect That Matters Most to Me: Muscle
Your scale can't tell the difference between a pound of fat and a pound of muscle. A DXA scan can, and STEP 1 ran one on a subset of participants.
The semaglutide group lost about 19% of their fat mass, which is great. But they also lost about 9.7% of their lean mass (2). Run the numbers, and that works out to roughly four of every ten pounds lost showing up as lean tissue, not fat.
That number needs context, and I'm not going to scare you with half the story.
A 2024 review of GLP-1 body composition data found lean mass loss ranging from about 15% to 60% of total weight lost across studies (8). Lean mass isn't only muscle; it also includes water, organs, and bone. Some loss is expected with any big weight reduction, and some evidence suggests the muscle that remains may be higher quality, with less fat infiltrated into it (8).
But the same review is clear about where the concern lies: older adults and people with more advanced disease face a higher risk of sarcopenia, the loss of muscle and function that makes people frail (8). That describes a lot of the people taking these drugs.
Muscle isn't only about how you look in a T-shirt. It's the tissue that:
Clears most of the sugar from your blood after a meal
Keeps you strong enough to carry groceries, climb stairs, and get off the floor at 75
Protects your joints, which matters a lot if you're training around an old knee, shoulder, or back injury
Drives a meaningful share of how many calories you burn every day
What Happens When You Stop
Here's the part the ads skip. In the STEP 1 extension, researchers followed participants for a year after they stopped semaglutide. They regained about two-thirds of the weight they'd lost, and most of their cardiometabolic improvements drifted back toward baseline (9).
Think about what that means. If you lose a meaningful amount of muscle on the way down, then stop the drug and the "bad" weight comes back; you don't automatically get that muscle back with it. Muscle has to be rebuilt on purpose. This is why you need to be resistance training. You also need to change your habits if you every want to stop taking the drug.
That's the scenario I'm trying to keep you out of. The same weight you started at, with less muscle than you started with.
Why Resistance Training Is the Missing Piece
This is where the evidence gets encouraging, and it's the whole reason I wrote this post.
In a 2017 trial in the New England Journal of Medicine, 160 older adults with obesity went through the same weight-loss program and were assigned to aerobic training only, resistance training only, or both (10).
Every exercise group lost the same 9% of body weight.
What they lost was different. The aerobic-only group lost 5% of its lean mass. The groups that lifted lost only 2–3%. Strength went up 18–19% in the lifting groups versus just 4% with cardio alone, and hip bone density followed the same pattern (10).
Same weight lost, very different bodies at the end.
The GLP-1 research points the same way. A 2021 trial took adults who had just lost weight on a low-calorie diet and assigned them for a year to an exercise program, the GLP-1 drug liraglutide, both, or placebo (11).
The combination group cut its body-fat percentage about twice as much as either the drug alone or exercise alone. It was the only group to improve blood sugar control, insulin sensitivity, and cardiorespiratory fitness. And gallstones and increased heart rate showed up more often in the drug-only group than in the drug-plus-exercise group (11).
The drug handles your appetite. Training decides what your body looks like and how well it functions, when the weight comes off. You want both.
What to Do If You're on a GLP-1
Lift at least 2–3 times per week. Full-body sessions built around the big movement patterns (squat, hinge, push, pull, carry) with progressive overload. Cardio is good for your heart, but it doesn't protect muscle the way lifting does.
Make protein non-negotiable. Suppressed appetite makes it easy to under-eat protein without noticing. When you're only eating half a plate, protein goes on it first. I break down how much you actually need in How Much Protein Do I Really Need?
Track strength, not just weight. If your lifts hold steady or climb while the scale drops, you're losing mostly fat. If your lifts fall off a cliff, something needs to change.
Measure body composition. A DXA scan or another reliable body-composition test at the start and every few months tells you what the scale can't.
Keep your prescriber in the loop. Your physician manages the medication. I don't, and neither should anyone selling you a training program. The best results come when the medical side and the training side are talking to each other.
Why I Can Be That Person for You
Here's where most people get stuck. The drug is doing its job. The weight is coming off. They know they should be lifting. But they're dealing with nausea on injection days, eating far less than they used to, and maybe training around a bad back or a shoulder that hasn't been right in years. Generic advice to "just go lift" doesn't account for any of that, so they don't do anything, and they lose muscle they can't afford to lose.
That's exactly why I built the Clinical Performance Method.
I'm a Doctor of Chiropractic with a master's in Sports Medicine, and I've been training people for over a decade. I don't prescribe your medication. That stays with your physician.
What I do is start with a clinical assessment of how you move, what your body will tolerate, and where your old injuries are. Then I build a strength program around your life: your energy on injection days, your appetite, your schedule, your joints.
Progressive, trackable, and designed so that the weight you lose is fat, not the muscle you'll need for the next 30+ years.
The shot can get the weight off. I'll make sure what's left underneath is strong.
If you're on a GLP-1, or about to start one, and you want to do this right, reach out and I will help you.
Luke Eddington, DC, MS, NASM-CPT/WLS
Apex Fitness Founder & Coach
Coaching starts with a discovery call. If you want to see what that would look like for you, send me a message on my socials or use the links below to contact me.
Precision Training | Proven Results
Discovery Call: Clinical Performance Method Call - Apex Fitness
Email: apexfitness@apexfitness.club
Instagram: apexfitness_llc_
TikTok: apexfitness_llc_
References
Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740-756. doi:10.1016/j.cmet.2018.03.001
Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038
Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med. 2023;389(6):514-526. doi:10.1056/NEJMoa2301972
Eli Lilly and Company. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials. News release. July 2026. investor.lilly.com
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563
Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M. Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss. JAMA. 2023;330(18):1795-1797. doi:10.1001/jama.2023.19574
Neeland IJ, Linge J, Birkenfeld AL. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes Obes Metab. 2024;26 Suppl 4:16-27. doi:10.1111/dom.15728
Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. doi:10.1111/dom.14725
Villareal DT, Aguirre L, Gurney AB, et al. Aerobic or resistance exercise, or both, in dieting obese older adults. N Engl J Med. 2017;376(20):1943-1955. doi:10.1056/NEJMoa1616338
Lundgren JR, Janus C, Jensen SBK, et al. Healthy weight loss maintenance with exercise, liraglutide, or both combined. N Engl J Med. 2021;384(18):1719-1730. doi:10.1056/NEJMoa2028198
Disclaimer: This article is for educational purposes only and is not medical advice. Dr. Eddington does not prescribe, dose, or manage medications. Do not start, stop, or change any medication without talking to your prescribing physician. Retatrutide is an investigational drug and is not FDA approved. If you experience severe abdominal pain, persistent vomiting, or other concerning symptoms while taking a GLP-1 medication, contact your physician immediately. Consult a qualified healthcare provider before beginning a new exercise or nutrition program.
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