The Pushback Against GLP-1 Agonists

(Above: From Wilding et al 2022 showing weight regain after stopping semaglutide injections.)

Announcement: I shall be LIVE on YouTube on Monday, November 10th, 2025 at 1 pm Eastern/12 pm Central/11 am Mountain/10 am Pacific to discuss the new insights coming at us that potentially solve many of the serious pitfalls and dangers—yes: dangers—of conventional weight loss methods. I will introduce many of the new concepts that I discuss in my new Super Body book. To attend this live event, sign up here. Everyone signing up will be sent an excerpt of the new book. The new concepts focus on SHAPE AND BODY COMPOSITION, not the now outdated concept of just weight loss.

Talk to the majority of primary care doctors, specialists, even professionals specializing in weight loss, and they gush with excitement over weight loss achievable with GLP-1 agonist drugs that go under names such as Wegovy, Mounjaro, Zepbound and others. Big pharmaceutical players are involved including Novo Nordisk, Eli Lilly, Pfizer, Amgen and other multi-billion dollar companies. Many doctors and telehealth companies have also joined the party, using ways to extract huge profits by dispensing these often very costly drugs typically not covered by healthcare insurance or Medicare for weight loss. An estimated 15 million Americans have already taken these agents, many more worldwide. We can’t blame them, intoxicated with the prospect of easy weight loss after years of struggle and failure.

But it’s not as if these drugs are being released into a vacuum of evidence. There is, in fact, abundant evidence that tells us that this has been a mistake, a mistake of huge magnitude that will not only cause accelerated deterioration of the health of millions of people, but also bring about earlier death by several years. I’m not referring to well-documented side-effects like nausea, vomiting, diarrhea, bowel obstruction, or thyroid cancer. I am referring to the distortions of body composition triggered by these drugs. GLP-1 agonists will induce substantial weight loss—that is not in question. But of the weight lost, 25% will be muscle, a huge amount. Someone who loses, say, 40 pounds will therefore lose around 10 pounds of muscle. Among the consequences of that much muscle loss are:

• Reduction in basal metabolic rate (BMR)—i.e., the rate at which your body “burns” energy to stay alive for the work of breathing, digestion, day-to-day physical activities, etc., an effect that persists for many years after weight is lost.
• The reduction in BMR guarantees weight regain when the drug is stopped. Few people can afford the cost of these drugs forever. Stop the drug and the weight will return as nearly all fat, little muscle. Someone who lost 30 pounds fat, 10 pounds muscle will therefore likely regain 32-34 or more pounds of fat, much of it in the abdomen, meaning you are more likely to be insulin resistant, become a type 2 diabetic, have hypertension, increased risk for coronary disease, dementia, breast cancer and other conditions. You paid several thousand dollars to become less healthy.
• We know from large databases (NHANES, EPIC Norfolk, ASPREE etc.) that have tracked tens of thousands of people who have lost weight, the majority of weight lost by reducing calories (through diet, bariatric procedures, and pharmaceuticals), will die several years younger than they should have, especially if weight loss was 10% or greater of total body weight. (For example, a 180-pound woman who loses 18 or more pounds.) Why? Weight loss typically leads to better blood glucose and blood pressure, reduced HbA1c, reduced abdominal fat, reduced inflammation, and other benefits. Why would earlier mortality result? The overwhelming likelihood is loss of muscle. Recall that loss of muscle not only hastens your death, but also means your last few years are more likely to be characterized by frailty, bone fractures, and loss of independence.

These issues are not my speculation; this has been borne out by extensive evidence. Billions of dollars are being made from the top-down by the pharmaceutical industry, pharmacy benefit plans, practicing physicians, telehealth companies. But YOU are the loser in this equation, losing not only control over health over the long run but also on your ability to stay alive and vigorous.

It’s all part of the effort to monetize health. For weight management, it began with the advice to “cut your fat and eat more healthy whole grains,” “everything in moderation,” “move more, eat less,” etc., NONE of which works, coupled with exploitative practices of the food industry, all of which led to the largest epidemics of obesity, type 2 diabetes, and other common conditions ever experienced in the history of our species. The medical system then comes to your rescue with bariatric procedures and weight loss drugs that monetize their mistakes while persuading you that they are doing you a favor.

The key is to therefore reject conventional wisdom: never reduce fat intake, never limit calories, do not include grains in your diet, do not use exercise to manage weight, and do not submit to surgical or pharmaceutica solutions for weight management. Instead, revert back to practices that allow, for instance, hunter-gatherer populations to be entirely free of both obesity and the “diseases of civilization,” as we do in my programs. If you need to lose weight, think instead about shape and body composition: don’t lose muscle, don’t allow BMR to drop, don’t set your life up for frailty, loss of independence, and early death. We do so by following a diet that mimics that of indigenous populations, restore nutrients (vitamin D, magnesium, iodine, omega-3 fatty acids, collagen, etc.) that you should have obtained from your wild diet, introduce factors that restore youthful musculature (and I don’t mean hours at the gym), then right the wrongs committed to your gastrointestinal microbiome including eradication of small intestinal bacterial overgrowth, SIBO, and the loss of keystone microbes that bring order and normal physiological support back to the microbes dwelling in your GI tract.

These are the ideas I explore in detail in my new book, Super Body: A 3-Week Program to Harness the New Science of Body Composition and Restore Your Youthful Contours available for pre-order prior to its anticipated release date of Dec 15, 2025 from the following retailers:

The original IHB post is currently found on the: ⎆Infinite Health Blog, but accessing it there can require an unnecessary separate blog membership. The copy of it above is complete, and has been re-curated and enhanced for the Inner Circle membership.