Just minutes after posting about the terrible effects of metformin on muscle mass, the study below pops up into my news feed (synchronicity again?) corroborating that blood glucose is not to be messed with on a whim. At least not if one cares about keeping their muscles – the primary factor determining one’s resting metabolic rate (RMR) and future risk of mortality/morbidity. Yet another “success” story from Big Pharma turns out to be nothing, but potentially another global health disaster in the making. Those companies just can’t help but create the perfect “Trojan Horse” drug every time, Namely, a drug that seems to have a striking effect initially in ameliorating symptom(s) of a given disease – obesity/diabetes in the case of metformin and GLP-1 agonists – yet in the background exacerbates systemic health so that the overall effects are profoundly negative, thus creating multiple secondary “opportunities” for the drugs that treat the side effects of the primary drug. Worse, in many cases the side effects of the primary drug are so terrible, it is arguably better to never take it in the first place. Some notable examples of such “blockbuster” stories from Big Pharma are the SSRI class of antidepressants, anxiolytic drugs (Klonopin anyone?), antipsychotics, proton pump inhibitors (PPI), statins, diabetes drugs such as metformin/phenformin, estrogenic HRT, 5-alpha reductase (5-AR) inhibitors such as finasteride/dutasteride, glucocorticoid therapy for inflammation, etc. This time, the new “blockbuster” disaster in the making seems to be the GLP-1 agonist class of drugs represented by flagship brand names such as Ozempic, Wegovy, Mounjaro, ZepBound, etc. Some of their side effects are already known and include apparently “acceptable” (according to whom?) increase in risk for conditions such as gastroparesis, blindness, and thyroid cancer. In addition, a recent study argues convincingly that GLP-1 agonists may cause pancreatic cancer when used long-term, and that cancer is lethal for the vast majority of people who get it. Yet, pharma companies can always fudge the stats to present the risk of such side effects as very low, thus convincing patients that the drug is worth it. However, what if the primary effect for which the drug is prescribed/marketed – weight loss – is another disaster in disguise? Wouldn’t that directly largely invalidate the very use case for such drugs? Worst of all, not only is this sacropenic side effect of GLP-1 drugs apparently known to medicine, the study below now confirms that the sarcopenic effects are very pronounced even in the heart muscle, which one of the most resilient to muscle tissue loss due to its high concentrations of anti-catabolic steroids such as testosterone, pregnenolone, DHEA and (in children and women) progesterone. And the cherry in the cake about this study is the recognition by study authors that muscle mass is one of the primary factors in controlling blood glucose and preventing development of diabetes (see my comment above about RMR). So, the current “blockbuster” drugs for preventing and treating obesity/diabetes actually excel at destroying the primary protective factor we have against obesity/diabetes (and CVD and mortality, and so on)!?!? Peak insanity, this can’t go on for much longer…
https://www.sciencedirect.com/science/article/pii/S2452302X24002869
“…The significant reduction in body weight (BW) induced by glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, has led to recent clinical trials demonstrating benefit in certain forms of cardiovascular disease (CVD).1 While these findings are promising for CV patients, a side-effect of GLP-1RAs use is the loss of skeletal muscle (lean BW) mass.2 Although it is likely that the metabolic benefits from weight loss may outweigh modest sarcopenia, this loss of lean BW could potentially lead to exercise intolerance that may reduce the quality of life in individuals at risk for or with heart failure.3 Given this, intense research efforts are ongoing to try to understand how GLP-1RAs induce loss of skeletal muscle mass.4 However, little attention has been given to the potential that other types of muscle, such as cardiac muscle, may also be lost in response to GLP-1RAs.”
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00272-9/abstract
https://www.ualberta.ca/en/folio/2024/11/weight-loss-drug-found-to-shrink-heart-muscle.html
“…Trendy weight-loss drugs making headlines for shrinking waistlines may also be shrinking the human heart and other muscles, according to a new University of Alberta study whose authors say should serve as a “cautionary tale” about possible long-term health effects of these drugs…Dyck and his team set out to study why a reported side-effect of the leading weight-loss drug Ozempic is the loss of skeletal muscle. Ozempic, known medically as semaglutide, was originally designed to help adult patients with type 2 diabetes control their blood sugar. However, this drug — and a host of others in this class of medication — are also being touted for their effectiveness as an anti-obesity medication. Using mice for the study, the researchers found that heart muscle also decreased in both obese and lean mice. The systemic effect observed in mice was then confirmed in cultured human heart cells.”
“…Dyck’s study comes on the heels of a commentary published in the November issue of The Lancet by an international team of researchers from the U of A, McMaster and Louisiana State University who examined emerging research showing that up to 40 per cent of the weight lost by people using weight-loss drugs is actually muscle. Carla Prado, a nutrition researcher in the Faculty of Agricultural, Life & Environmental Sciences and lead author on the commentary, explains this rate of muscle decline is significantly higher than what is typically observed with calorie-reduced diets or normal aging and could lead to a host of long-term health issues — including decreased immunity, increased risk of infections and poor wound healing. “Muscle does much more than just help us move or lift things. It is a powerful organ that keeps us healthy in a number of ways,” she says. For example, muscle stores important building blocks — amino acids — that the body uses when we’re sick, stressed or injured to repair itself and stay strong. It also plays a huge role in managing blood sugar, which helps prevent diabetes. As well, Prado notes muscle releases special molecules called myokines that signal other parts of the body to help fight infections and support our immune system. “That’s why preserving muscle is so important, especially during weight-loss treatments — it’s not just about staying strong, but about keeping our whole body resilient and healthy.” In the commentary, the authors suggest that muscle loss due to weight reduction may also exacerbate conditions like sarcopenic obesity — characterized by a combination of high body fat and low skeletal muscle mass — which contributes to poorer health outcomes, including cardiovascular disease and higher mortality rates.”
