Newly Discovered Compound Prevents Ozempic Muscle Loss - Dr. Kyle Gillett

Thomas DeLauer, the host, shares his personal practice: he uses sugar-free creatine stick packs (Create brand) sweetened with monk fruit and sips them throughout the day. He prefers micro-dosing because the literature suggests that large boluses are associated with the water retention that many users dislike. Dr. Gillett agrees and adds that even with standard monohydrate, the initial water retention subsides significantly after a few weeks of consistent use. He notes that women especially may abandon creatine after a one-week bump in scale weight, missing the long-term muscle preservation benefits—a persistent problem he sees clinically.

Dr. Gillett explains that when patients want to drop weight, many women gravitate toward excessive cardio and many men toward only lifting. He jokes that you should 'switch their regimens' — give men some cardio and women resistance training. He stresses that the biggest lever to prevent excessive fat or muscle loss is actually the dose of the GLP-1 drug; using the lowest effective dose or switching to a weaker GLP-1 like tirzepatide may be as important as exercise. However, he emphasizes that resistance training remains a cornerstone of preserving muscle quality during weight loss.

Dr. Gillett acknowledges that a decent number of people cannot tolerate creatine monohydrate due to GI side effects. In his clinical practice, he has had patients anecdotally do better with liposomal creatine or with creatine HCl (crealkaline). He stresses that just because monohydrate is the expert consensus 'best' does not mean a person should not try another type if the standard form is problematic. This is especially important for patients on GLP-1 agonists, who may already have slowed GI transit and increased sensitivity.

Dr. Gillett notes that many people on GLP-1s develop an aversion to fats and may not be digesting the fat they do consume because the drug has slowed their GI tract. In his practice, the sports dietitians will have patients taste a bitter substance before eating to kickstart their own enzymes rather than relying on supplemental digestive enzymes. He jokes that functional medicine companies would rather sell enzymes, but this trick costs nothing. He also recommends eating the most nutrient-dense foods first so they pass through the stomach before it becomes too sluggish. If fat tolerance remains an issue, lowering the GLP-1 dose is the primary strategy.

Dr. Gillett describes that in large trials like SURPASS, ~80% of participants regained significant weight, often more than half of what they lost, when the drug was stopped abruptly. However, real-world studies that aggressively implemented diet and exercise alongside a taper saw only about 50% regain. In his own practice, fewer than half of his patients regain weight because he tapers everyone off and uses the time to embed lifestyle habits. He is critical of 'cookie-cutter GLP-1 clinics' that simply write prescriptions without this behavioral component, warning that the drugs should be a crutch while the leg heals, not a permanent wheelchair.

When Thomas DeLauer raises the concern that many GLP-1 users develop a distaste for fats, Dr. Gillett confirms this is a 'pretty major issue.' He points out that most Americans already consume too many omega-6s and too few omega-3s, and GLP-1s can worsen this by causing people to avoid all fats. At the same time, the drug's effect on gut motility can either speed up or dangerously slow down transit, leading to gastroparesis or ileus. He suggests that ensuring a nutrient-dense meal is consumed early while the stomach is still moving, and stimulating digestive enzymes with a bitter tastant, can help. If fat aversion persists, it's a sign that the dose is too high.

Dr. Gillett explains that the study included about 150 individuals and was well-designed and placebo-controlled. The group receiving semaglutide plus ostarine preserved lean body mass and also maintained the ability to climb hills or stairs, a functional outcome that matters for quality of life. He clarifies that this does not mean people can stop eating enough protein or doing resistance training, nor does it permit taking the highest possible dose of GLP-1. However, it represents a leap forward because it studies a molecule previously used mostly for prostate and breast cancer in a new, functional context — essentially as an atypical hormone replacement therapy that targets muscle without the full-body effects of testosterone.

Dr. Gillett walks through the mechanism: the androgen receptor is a single receptor that testosterone and DHT bind. Ostarine binds the same receptor but selectively activates it in muscle and bone while deactivating it in tissues like the prostate. He compares it to selective estrogen receptor modulators (SERMs) like Clomid and tamoxifen, which activate or block estrogen in a tissue-dependent manner. He emphasizes that women can still virilize from ostarine because it drops sex hormone binding globulin (SHBG), freeing androgens and accelerating testosterone metabolism. This leads to predictable side effects: low testosterone and estrogen on labs, elevated LDL and liver enzymes, and a suppression of natural testosterone that can last weeks post-cessation, often causing a 'crash' feeling.

Dr. Gillett explains that among the different GLP-1 class molecules, there is a spectrum of growth hormone release. The triple incretin retatrutide, by including glucagon, is likely the most potent stimulator of growth hormone. This could be advantageous for someone with low growth hormone, but he warns that if a person has an active tumor, excess growth hormone is undesirable — echoing the caution that led to a decline in off-label HGH use after the 1990s. He also mentions other drugs like liraglutide (generic, daily injection) and dulaglutide (once-weekly, but on shortage) as alternatives with different profiles.

During a discussion on DPP4 inhibitors and whether foods that inhibit DPP4 (like fiber- and protein-rich foods) meaningfully prolong endogenous GLP-1, Dr. Gillett points out that GLP-1 is a gustatory peptide. Two people could eat the same food, but if one enjoys it more, they might have a more pronounced or delayed GLP-1 effect. He uses fat as an example: most high-fat foods produce a GLP-1 rise 12–18 hours later, but the magnitude can vary with palatability. He also notes that liquid fats, like those in bulletproof coffee, can be consumed very quickly before any satiety peptide kicks in, leading to overconsumption.