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I take 1.25 milligs of despatite every week. So I'm a 34 year old GP. I don't have type 2 diabetes. I'm not overweight. And there is no randomized clinical trial that said I should be doing this.
Every trial that you may have heard of, so select or flow surpass COVT. They enrolled people with diabetes, obesity, kidney disease, or established heart disease. None of them studied someone like me. So here's why I inject anyway.
So when John Ing found GLP-1 in the saliva of the Hila monster in the early 1990s, all it was supposed to do was lower a blood sugar, he was an endocrinologist in Bronx VA and he was working on lizard venoms in his spare time. But the peptide that he isolated, it acts on the same receptor as the human GLP1, but it lasts much longer in the body. But in the early diabetes trials, not only did patients lower their blood sugar levels, which was expected, but they also started to lose significant amounts of weight. So again, it wasn't just a little bit, it was a lot and it was enough for doctors to start to notice. And by the mid-2010s, the scale trial had confirmed that luraglutide, which is another type of GLP-1 medication, caused significant weight loss. And by 2021, the step program tested semiglutide, which you may know as a higher 2.4 milligram dose for obesity. So this trial, it wasn't involving type2 diabetics. It was just for obese patients, and it resulted in around 15% of body weight loss. The GLP-1 medications had graduated from just a blood sugar drug to a weight loss drug. And the field assumed quite reasonably that every benefit from here on out would just be downstream of the weight coming off. But that is not what the trials found.
So here is surprise number two. November 2023, the select trial. It involved more than 17,000 adults who were overweight or obese with established heart disease but no diabetes and they were randomized to weekly simaglutide or a placebo. And a little more than three years later, semiglutite, it cut major cardiovascular events by 20%. So this is in people remember without diabetes. And when the trialists ran the numbers separately for people who lost a lot of weight versus very little, a chunk of the cardiovascular benefit did not track with how much weight came off. So this is important here. The GLP1 medications, they appeared to offer cardiovascular benefits beyond the weight loss effect.
So here is surprise number three. May 2024, the flow trial. It involved about 3,500 adults with type 2 diabetes and chronic kidney disease. So again, it was semiglutide versus a placebo. And the primary outcome, which was a combination of kidney failure rates, large EGFR drops, kidney or cardiovascular death, it dropped by 24%. And the author said something specific here. The effect on kidney health was unrelated to changes in body weight. So again, the weight loss was not the whole story. GLP-1 medications were offering additional benefits. And now there's even new evidence that GLP-1 medications are associated with a reduction in cancer progression.
So surprise number four, and this one is remarkable. Cartilage, it's got no blood supply. It's got no nerves and no efficient way to deliver cells the nutrients it needs to grow new tissue. It's one of the few structures in the human body that once it's damaged, it's severely limited in its ability to repair itself. But then patients on GLP-1 medications, specifically this time a Zmpic, they started saying something that their doctors initially dismissed that their joints felt better. And it wasn't just less pain from carrying less weight. It was something else, something unexpected. So the obvious explanation again is just weight loss that the less weight you have means the less mechanical pressure on the joints. So every kilogram that you lose, it takes roughly 4 kg of stress off your knees. So whenic patients reported less joint pain, doctors shrugged and said, "Well, of course your knees hurt less because you lost 30 lbs." But in the step 9 trial, which was published in the New England Journal of Medicine in 2024, it seemed to confirm this. 47 patients with obesity and knee osteoarthritis. And after 68 weeks, pain scores dropped by 42 points in the semiglutide group compared to 28 in the placebo group. But patients, they also lost 13.7% of their body weight. So it seemed that was case closed. But a team of researchers at the Shenzhen Institutes of Advanced Technology, which is part of the Chinese Academy of Sciences, it wasn't satisfied with that explanation. So led by Dr. Dai Chen, they designed an experiment that would test this theory directly. So this is the study that changes the conversation. So Chen's team, they took mice with osteoarthritis and they split them into two groups. So one group received semiglutide but another group was peerfed meaning that they were given restricted calories carefully controlled so that they lost the same amount of weight as the semiglutide group. So again same weight loss but with no drug. So if the joint improvements were just weight loss then both groups should look the same but they didn't. The pefed mice lost the same amount of weight but their cartilage kept deteriorating only in the semiglutide group. There it showed preserved cartilage, reduced inflammation and fewer bone spurs. So again, it was the same weight loss but a completely different outcome in the joints. Dr. Chen explained the implications. This controlled experiment demonstrates that semiglutide's protective effect on cartilage in osteoarthritis is independent of weight loss and challenges the traditional belief that osteoarthritis improvement relies solely on weight reduction.
So if it's not the weight loss, then what is happening? Well, here's the simplest way to think about it. Your cartilage cells called chondroites, they need energy to maintain and repair the tissues around them. In osteoarthritis, those cells, they get stuck running on an inefficient fuel source. So, think of it like a factory running on a spluttering generator. It's barely enough energy to keep the lights on and not nearly enough to rebuild anything. So, what semiglutide does is flip a switch inside those cells that upgrades them to a clean, efficient energy source that produces dramatically more energy, enough to actually start repairing. And it's activated by GLP-1 receptors on the cartilage cells. So again, we were not anticipating that GLP-1 receptors would be on cartilage cells, but here they are. But Mel's cartilage of course is not human cartilage. So does it actually work in people? Well, Jen's team, they ran a pilot clinical study. So 20 patients aged between 50 and 75, all with obesity and knee osteoarthritis. Half of them received standard treatment with hyaluronic acid injections and the other half received hyaluronic acid plus weekly semaglutide. After 24 weeks they put them in MRI scanners. The semiglutide group showed an average 17% increase in cartilage thickness suggesting regeneration. The control group on the other hand they lost about 1%. So the thickened cartilage was visible in weightbearing areas of the knee the areas that take the most punishment. Patients also experienced reduced pain and improved joint function. And to finish the benefit list, we see benefits for the liver and for addiction.
But what we've discussed so far is evidence for GLP-1 medications. But I chose to use toepide, which is a combination of GLP1 and GIP. So why did I do this? Well, that brings us onto the final piece of the discovery arc, the trial that compares the drug classes against each other for the first time. So surpass COVT. It was published in two stages. The primary outcome in the New England Journal of Medicine was published in December 2025 and a follow-up cardioral analysis in JAMA cardiology in March 2026. So to zepatide which again is a jewel of GLP-1 and GIP versus dulaglutide which is a pure GLP1 13,000 patients with type 2 diabetes and established heart disease followed up for just over 4 years. Here is the part that the headlines did not put first. The primary endpoint was the classic threepoint mace. So cardiovascular death, heart attacks or strokes toepide did not beat dulaglutide on that endpoint. It cleared the no worse than bar cleanly. But on the harder question of is it actually better, the result came in short of the threshold that the researchers had committed to before the study started. So by their own rules going into the study, it counts as a miss. But here's the part that made the conversation. The same investigators they ran an after-the-act or post hawk analysis in JAMA cardiology 2026 they widened the endpoint to six components. So they added in heart failure hospitalization coronary revascularization all cause death and arenal composite to the original three. So on that wider end point to zepatide it reduced risk by 16% relative to dullutide. So for me personally, that was enough to want the combination of GLP-1 and GIP compared to just GLP-1.
None of these studies enrolled lean non-diabetic adults. The bet I'm making is narrower. So across several studies, these drugs, they seem to produce some biological effects that are partly independent of the weight loss effect itself. And I'm interested in exposing myself to those potential mechanisms. And I'm not the first physician to publicly disclose this. So Dr. Michael Albert who's a US internist he wrote about taking lowd dose to zeppetide for 2 years in March 2026 and he framed it as a personal choice not a recommendation which is what I'm doing here as well but then the next logical question is why have I chosen to zeppitide and not the new triple agonist called retatrutide so retatrutide has got a third component that acts on glucagon receptors so glucagon agonism it increases metabolic rate so for an obesity drug at a population level that is a feature but for me Trying to maintain lean muscle mass and not burn any of it. Pushing energy expenditure up for me is the wrong direction. With that rise in metabolic rate comes a dose dependent rise in resting heart rate. 3 to seven beats per minute in a phase 2 trial to zepatide. Yes, it does raise heart rate typically about 2 to four beats per minute, but it's not as much as retride. And with that rise in metabolic rate, there are some concerns about the cardiovascular risk profile with retatrite. And we're still waiting that data to come out. So for me, I don't want to take something that speeds up my metabolic rate when I don't necessarily want to. Again, I'm not trying to lose weight necessarily.
So coming back to lowd dose to zeppetide, since I've been using it, I have noticed a significant drop in food noise. So it's way easier to stick to a healthy diet because the cravings for junk food, they're just gone. Plus, I've got genetically high blood pressure. And since using Tiseptide, I've managed to cut my blood pressure medication doses in half. It did make me feel pretty rubbish, though, when I first started it. So, I felt nauseous and I felt tired. But with each injection, the side effects lessened and now I've got no side effects whatsoever. And I look after my muscle mass via resistance exercise and good protein intake.
Now, there are a few other safety concerns that I needed to factor into my decision before I started to zepide. So, there was a concern about pancreatitis. However, from the real world data, there's been no increase. There's also no signal of increased risk of thyroid cancer from the real world data and the FDA and EMA which is the European drug regulator. They both reviewed the suicidal signal in 2024 and they found no casual link. And the final concern with GLP-1 medications is micronutrient levels. So I am eating less food since being on lowd dose toeptide and I've lost about 3 kg over a 9-month period. So on a GLP-1, the daily calorie intake, it typically drops by between 16 to 39%. And the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and the Obesity Society, they suggest to consider a multivitamin and mineral tablet, which is part of the reason why I take microvitamin every day. And microitamin has now been thirdparty tested by labdor.com, and it scored a 99.7% score. But just because I take a supplement does not mean that you should as well.
Overall, I'm happy with my bet on lowd dose despatite and I plan on taking it long-term. But if you're interested in gaining some of the health benefits that I've touched on here, particularly when it comes to heart health, then there's something that you can do that is not off label and it's supported by mountains of data. Of course, I'm talking about exercise, but most people don't know how little exercise they can do to actually yield significant benefits. So, make sure to check out this next video here to discover how the newer studies based on actually tracking activity caused me to completely rethink the advice that I give to my patients.