Many people by now have heard of the 'miraculous' GLP1 drugs which include the original Ozempic (Semaglutide), and of course Mounjaro (Tirzatrupide). Semaglutide was the original GLP1 agonist which was released to help diabetics reduce their blood sugar and weight. Tirzatrupide is similar in how it works, but it adds a second component against GIP. The two work synergistically to reduce appetite and improve insulin handling.

I'm one of those unfortunate people that has always struggled with my weight, despite trying my best to exercise lots of get outside as often as I can. Starting from about the age of six, I started mostly being stocky. That continued on into high school, and just sort of became my identity. Despite playing on three high school team sports simultaneously - badminton, tennis, and rugby - I never managed to obtain what other people would probably think was a normal weight.

I remember one time in physical education class - despite pushing myself to be in the top five for every run, scoring as many goals as I could, playing as many team sports as I could, the teacher still gave me a "C" grade for my final report. When I challenged her on it, asking why when I was always one of the first to finish any race or event, she would give me a C, and yet she gave As to some of the slackers in the class, she didn't have an answer. But of course the truth was she saw me as unfit and out of shape, and graded me with that bias.

It never got any better for me into adulthood either. My last serious girlriend weighed about 115 lbs and was from Brazil. Despite us eating most of our meals together for two years, and me being twice her weight, she basically stayed the same weight and I continued slowly plumping up during that time. Occasionally she would mention it like I somehow was defying the laws of physics, which is how it feels sometimes. When we visited her family in Brazil for a month, we mostly just ate rice and beans that her mom cooked, and I still gained weight.

The only time really where I managed to get down to a lower weight was when I first tried the Atkin's diet in my 20s. Over the course of about four months I dropped from 216 lbs down to about 176 lbs. That's still heavy for a 5'9" frame, but I've always had a ton of muscle. Outside of that brief period, and another six months where I also lost weight low carbing as an adult, I've always mostly just accepted this was my fate, despite wishing that wasn't the case.

In 2017 I walked 800 kms across Spain on the Camino de Santiago. I did it in 28 days, which was close to 30kms a day of walking. Lots of people report losing 20 - 30 lbs in a month, since they are likely average 2,000 calories a day of exercise. I probably did lose 5 lbs or so, and maybe firmed up quite a bit (trail hardy, as they say), but I mostly kept the same weight despite my best efforts.

The thing is, paradoxically I'm not that unhealthy. Lots of heavier people end up with horrible blood sugars, diabetes etc. I've never had that issue. My last HbA1C was about 4.8%, and my fasting insulin was less than 9. I have no idea why this is, other than perhaps that I gave up sugar and most simple carbohydrates over 20 years ago. But even when I've optimized my throid and my testosterone levels, my body just doesn't want to give up the goods.

The problem is even if someone like me sees a nutritionalist, which I've done, they never believe you aren't just pounding back sweets when they aren't looking. I even once took photos of all my food and put it on Dropbox for the nutrtionalist to see, and even with the evidence she still couldn't be convinced I wasn't snacking somewhere else. I don't even really have a sweet tooth to be honest, and my cupboards at home are mostly devoit of any snacks, baked goods, etc.

GLP1 To The Rescue

By now almost everyone has tried or knows someone who has tried one of the GLP1 medications (Ozempic, Mounjaro, etc.) that aid in weight loss. GLP-1 medications started with the discovery of glucagon-like peptide-1 (GLP-1) in the 1980s as a gut hormone that stimulates insulin release in a glucose-dependent way. Early attempts to use native GLP-1 failed because it’s rapidly broken down in the body by the enzyme DPP-4. The breakthrough came in the 1990s with the identification of exendin-4, a GLP-1–like peptide found in the saliva of the Gila monster lizard. This led to the first approved GLP-1 receptor agonist, exenatide (Byetta), in 2005, which showed strong glucose-lowering effects and modest weight loss. Over the next decade, pharmaceutical development focused on longer-acting analogs such as liraglutide (Victoza), dulaglutide (Trulicity), and semaglutide (Ozempic, Rybelsus, Wegovy), each designed to extend half-life and improve convenience (e.g., daily vs. weekly dosing).

From the late 2010s onward, GLP-1 agonists evolved beyond diabetes care into obesity treatment, driven by evidence of significant and sustained weight loss. Liraglutide gained approval as Saxenda for obesity in 2014, followed by semaglutide as Wegovy in 2021, which produced unprecedented weight-loss results. The field has since expanded into dual and triple agonists (e.g., tirzepatide [Mounjaro, Zepbound] and retatrutide) that target GLP-1 alongside other gut hormone receptors like GIP and glucagon for greater metabolic effects. Today, GLP-1–based therapies are not only central to type 2 diabetes management but are also reshaping obesity treatment and being explored for conditions ranging from fatty liver disease to cardiovascular risk reduction.

My First Attempts: Ozempic + Mounjaro

At one point I figured since everyone was talking about it, that I should try Ozempic. So I just went down the pharmacy to get it in Spain. I worked my way up from the lowest dose to probably the third dose from the bottom. Despite it mostly killing what was left of my appetite (I've never been a big eater really anyways, which is another part of the mystery), I didn't really any weight. I probably should have waited a bit longer and increased the dose a bit more, but since I wasn't really that hungry and my blood sugars weren't really in need of improvement, I wasn't sold on spending that amount of money every month.

When Mounjaro came out, probably a year or 18 months later, I decided to give it another go to see if it was any better. Sure enough, it killed my hunger, lowered my blood sugar slighty (I went from a HbA1C of 5.0 down toe 4.8), but still didn't help get the pounds off. Once again, spending 400 euros a month on a medication that wasn't really helping didn't seem too appealing to me, so I started investigating a bit more.

GLP1's New Friend: Glucagon

Retatrutide is a new peptide coming likely in the 2026 that contains a GLP1 and GIP agonists, just like Mounjaro, but also adds a glucogan component as well, which is where its magic will likely come from. Glucogan is a hormone that basically tells the body it needs to burn fat. What typically makes glucogan rise in humans is the absence of insulin, and it is why glucogan often rises during the night or when insulin is finally reduced via a low carb diet.

It turns out if you increase glucogan, even artifically, it will tell the body it needs to burn fat. One of the immediate benefits of this is the very rapid liquidization of liver fat, something that up until now has been hard to address. Other than diet and exericse, there weren't any real treatments that could reverse fatty liver disease, certainly not to any great extent.

In recent trials of retatrutide, the mean reduction in liver fat over a period at 24 weeks (6 months) was -49.2% at 1mg, -57% at 4mg, -81.4% at 8mg, and -82.4% at 8mg/week. Stated another way, the drug almost completely liquified and reversed liver fat at doses above 4mg/week in just a short six month period. That's absolutely incredible, especially considering up until now there haven't been many treatments for fatty liver disease.

In addition, glucagon itself can raise the body's resting metabolic rate slightly. Many obese people, especially ones that have been weight reduced via diet previously, have lower than predicted metabolic rates (also known as metabolic adaptation). Conceivably this bump in resting metabolic rate might help offset that, making it easier to slim down even without massive changes in food intake. While they are still doing trials and measurements, the predicted increase in RMR is likely somewhere around the 200-300 kCals per day mark. That may seem like a small effect, but it amounts to upwards of 30 lbs of fat in a single year.