By now, most of you recognize that conventional weight loss advice—cut your calories; move more, eat less; everything in moderation; eat many small meals every two hours throughout the day, etc.—is ineffective and does not lead to long-term weight loss success. In fact, it is well established that such advice does not work and causes health to deteriorate, not to mention it makes you miserable, fighting against the incessant hunger it creates. Useless advice from healthcare providers therefore opened the door to pharmaceutical agents and bariatric procedures for weight loss, incentivizing healthcare providers to the flow of revenues into their pockets.
The new class of GLP-1 agonist drugs, such as Ozempic, Wegovy, Rybelsus, and Mounjaro, are skyrocketing in popularity due to their weight loss effects. People are scrambling to obtain these drugs, anticipated to be a $19 billion/year opportunity for the pharmaceutical industry in short order. Despite their popularity, I question whether these drugs should have been approved by the FDA in the first place, given their long-term potential for destructive health effects. So let’s consider this wildly popular class of drugs and the effects they wreak on health.
Originally intended to reduce blood glucose in type 2 diabetics, it was noted that substantial weight loss also occurs. In one recent clinical trial, for example, once weekly injections (only Rybelsus is oral; all others are injectable) led to 52 pounds lost over a year and a half. This ignited wild and unprecedented demand for these drugs, so much so that many weight loss programs like Weight Watchers, Noom, and Calibrate embraced the drugs, adding them to their programs (making you wonder, if all these programs have to rely on a drug, what’s the purpose of the program when you can just go to your primary care doctor and get a prescription?). Three drugs in this class, Wegovy, Saxenda, and Mounjaro, have been FDA-approved for a weight loss indication, while the others are used off-label, meaning that healthcare insurers will need to decide whether they will cover the costs of the drugs approved for weight loss, spreading out the costs to you and me as payers of healthcare insurance premiums.
Let’s put aside the side-effects (nausea, vomiting, diarrhea, pancreatitis) and absurd costs (typically $1000 to $1500 per month). Let’s consider the long-term consequences of taking these drugs.
Say you spent around $15,000 over one year by injecting one of these drugs and lost 30 pounds. Of that 30 pounds, about 50% of lost fat is subcutaneous (buttocks, thighs, arms, chest, etc.), 50% is abdominal visceral fat, the fat responsible for most of the problems associated with excess weight (insulin resistance, type 2 diabetes, cardiovascular risk, fatty liver, increased risk for Alzheimer’s dementia, breast cancer, stroke, etc.). In other words, the drugs are not selective for the most problematic form of fat, abdominal visceral fat. Metabolic benefits on blood glucose, blood pressure, etc. are therefore limited. Recall that abdominal visceral fat, not subcutaneous fat, is responsible for generating insulin resistance that causes weight gain, blocks weight loss from fat stores. Preferentially losing abdominal visceral fat that leads to reduced insulin resistance would therefore accelerate weight loss; the GLP-1 agonists are not selective for abdominal visceral fat.
Another problematic issue: Of the 30 pounds lost, approximately 10 pounds is muscle—that’s a lot of muscle. Think about 10 pounds of beef and losing that amount from your arms, chest, back, thighs, face. Not only are you weaker, less confident in navigating stairs, hiking, carrying out lawn work, etc., you are also more prone to falls, fractures, and frailty over time. Muscle mass is the primary determinant of basal metabolic rate (BMR), i.e., the rate at which your body “burns” calories to sustain the work of breathing, gastrointestinal digestion, maintenance of body temperature, etc., body activities that are ongoing and beneath conscious direction. Loss of muscle therefore typically leads to 15-27% reduction in BMR, an effect that persists for many years after muscle loss. It is a survival mechanism: a reduction in calorie intake is perceived by your body as a lack of resources, starvation, and metabolic rate is reduced to ensure your survival. But it also guarantees weight regain—even if you maintain a low-calorie lifestyle. Losing muscle mass with weight loss is therefore a pivotal and crippling development of any method of reducing calories, whether it’s a GLP-1 agonist, a bariatric procedure, or calorie restriction. You will regain the weight.
Worse: When you regain the weight, it is mostly fat. Of the 10 pounds of muscle you lost, you will regain, at best, 5 pounds of muscle along with around 25 pounds of fat. You are therefore in worse shape metabolically after the drug than you were before taking it. Your risk for conditions such as coronary heart disease and heart attack, type 2 diabetes, cognitive impairment and dementia, breast cancer, hypertension and others is increased. Had the FDA required long-term follow-up evidence for the effects of these drugs, they would have likely recognized that these drugs increase mortality, i.e., they increase potential for numerous diseases and shorten your life.
With GLP-1 agonists, you therefore have a choice: Stop the drug after spending thousands of dollars and regain the weight or stay on the drug forever, paying the pharmaceutical industry hundreds of thousands of dollars over time to maintain your more slender weight. Imagine a cancer chemotherapy drug that does not cure the cancer, but keeps it from growing and metastasizing. Stop the drug and the cancer grows and spreads, eventually killing you. Stay on the drug at the cost of many thousands of dollars and it keeps the cancer controlled. You are, in effect, held hostage by the drug and the pharmaceutical company. This is how it is with the GLP-1 agonists.
And wait until all those Hollywood types who inject GLP-1 drugs to lose weight recognize what happens to your appearance when you lose subcutaneous fat and muscle from the face and elsewhere: You look 10-20 years older.
Yet methods to specifically target loss of abdominal visceral fat are available. Ways to increase lean muscle mass without exercise are available. In short, you are able to achieve slenderness, restore youthful muscularity, enjoy normal healthy body composition. But it won’t involve drugs, procedures, or the misguided advice of your doctor. Go back through the many discussions I’ve posted in this blog and elsewhere and you can save your $15,000 and avoid adverse health effects while enjoying youthful slenderness. The ideas I originally articulated in my Wheat Belly books are a start. But, since then, the strategies we use to regain youthful body composition—boost oxytocin with restoration of L. reuteri, push back SIBO by restoring microbes that colonize the small intestine and produce bacteriocins, add the body-shape modifying effects of collagen peptides and hyaluronic acid absent from modern lifestyles, and others, all natural but lacking in most people’s lives—are available, effective, safe, and restore multiple aspects of health and youthfulness.