In our era of conveyor-belt, drug-based medical treatment, few primary care physicians have the time or inclination to look much beyond the numbers on a blood test. Make the diagnosis, write the prescription and problem solved. Or is it?  

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Like any good functional medicine physician, I prefer to focus on uncovering the root causes of disease and working with the patient to develop a customized, more holistic approach to healing, calling in pharmacological support only when it’s strictly medically necessary. In other words, I’m not big proponent of using the prescription pad as your first line of defense.

However, some ills are more stubborn than others, and for millions of people, excess weight is one of them. I’m not talking about an extra 5-10 pounds that may interfere with how you want to look in a bathing suit. But more significant weight issues (the current definition of obesity is a BMI of 30 or higher, as flawed a measure as BMI may be) will typically, over time, drag your heath down, especially your metabolic health. Most people who are seriously overweight are at least pre-diabetic and many of them will cross the line into type 2 diabetes, dramatically increasing their odds of developing a life-threatening cardiovascular condition.

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This may surprise some of my readers but I’m not opposed to these weight-loss drugs when used appropriately. In fact, for patients and readers who have tried and failed for years to control their weight by changing their diets and lifestyle, I’d say they have the potential to be game-changers. Not as a replacement for a healthy lifestyle but in addition to it. Also remember they can be difficult to get off, and that in order to maintain your weight loss, you may well have to take the drugs in perpetuity. So, prepare to make a commitment, the same way you would if you went on blood pressure meds. Here’s the skinny on what you need to know to help you weigh the options:

1) What in the world is a GLP-1 agonist?

The semaglutide in Ozempic and Wegovy mimics and amplifies the effect of a natural hormone produced by the gut, GLP-1, a kind of “Swiss Army knife” hormone which affects a lot of important things. The pharma boost to the hormone slows down the passage of food through the stomach which extends the feeling of fullness after a meal and it also directly tamps down hunger, appetite and cravings at the brain level. The result: you feel less hungry, you eat less food, you lose excess weight. That’s good all round: for your joints, for protection against cancer, quite possibly for your emotional health and certainly for your metabolic health. Compounding the metabolic benefits, the drug prods the body to produce more of its own insulin, helping to keep blood sugar under control. The diabetes drug Mounjaro, which, like Ozempic, has not yet been approved by the FDA for weight-loss, contains a different chemical compound that acts on GLP-1 as well as another gut hormone pathway. The Mounjaro studies have recorded those 20% body-weight reductions, which is nothing short of amazing.

2) How are GLP-1s taken?

At present, the drugs are administered by patients themselves, via a once-weekly injection pen, injected into either the thigh or abdomen. Most patients start with a low dose, say a 2.5 mg shot for four weeks, stepping up each month in 2.5 mg increments, all the way up to 10 – 15 mgs per weekly shot, depending on their response. There are pill-form GLP-1’s, for example Rybelsus, which is also designed for blood sugar control. But so far, the current pill formulations tend not to result in the significant weight drops seen with the injectable versions.

3) What to expect with GLP1 agonists?

The good news is that, in addition to numerous clinical trials, GLP-1 drugs have been in use for more than a decade to treat diabetes and for about eight years as an obesity treatment – so they are not a terrible bet, safety-wise. But, as with virtually all pharmaceuticals, there are side effects, which can come as a surprise to those just starting out. One of the biggies is simply not feeling very good on them — gastrointestinal discomfort like nausea, constipation, diarrhea, gas, and vomiting top the list, along with fatigue, usually felt most strongly in the initial dosing phases, when patients are ramping up and acclimating to the drug. For most people those issues subside over time, but acclimating can be tough for some, ranging from uncomfortable to intolerable, or bad enough to stop treatment altogether.

4) What are the pitfalls?

Beyond the more everyday side effects outlined above, there are a few less talked about ones that are not that infrequent and that concern me more. They are: malnutrition, muscle loss, gastroparesis (or stomach paralysis) and the risk of mood disorders.

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First up, with GLP-1 drugs, weight loss often happens relatively quickly, and who doesn’t like the sound of that. However, if appetite becomes too suppressed by the drugs, patients may wind up eating fewer calories than their body needs to maintain healthy function and prevent fatigue – so every morsel you consume while on the drugs needs to be as high in nutrients as possible. Patients may need to add a nutritionist well versed in GLP-1s to their team to advise on food choices and develop a specific eating plan.

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Another reason to pay very close attention to nutrition while on these drugs: not only will you lose fat, you’ll also shed muscle, which happens with virtually any big and/or speedy drop in weight. To offset muscle loss, I highly recommend getting plenty of protein in your diet and adding resistance training to your exercise mix, at least three times a week. As the New York Times recently reported, the muscle loss associated with GLP-1 drug use is particularly concerning in adults 50 yrs and older, whose muscle mass and bone density is typically declining due to aging anyway, increasing the risk of fractures and falls, even fatal ones. Adding more muscle loss on top of the aging-related loss can be a dangerous game, so I can’t stress enough how important it is to slow the slide with more protein and resistance work.

5) Lost pounds can come at a price.

If you’re paying out-of-pocket, GLP1 agonists are very, very expensive. With Ozempic and Wegovy averaging anywhere from $900 – $1200 for a one-month supply, the cost alone can put these drugs out of reach for many people. With the soaring popularity of the GLP-1s, insurers are growing increasingly reluctant to pick up the tab. Doing so for even a fraction of their eligible overweight customers could potentially bankrupt them. However, if you are dealing with obesity and diabetes –  which often go hand-in-hand — chances are much better that your insurer will pay for a GLP-1. It’s a fluid situation. Some experts believe these prices will come down as more weight-loss drugs hit the market over the next few years.

6) Final thoughts

GLP-1 agonists are changing the landscape of weight loss as we know it, with the potential to enable millions of people to live better and healthier lives, truly life changing. But the drugs need to be used as wisely and thoughtfully as possible, and as with all drugs, one must assess if the benefits outweigh the potential risks. And, like all peptides, I have seen the GLP-1 agonists, in particular Tirzepatide, have many other downstream positive effects in addition to weight loss. I can see low dose Tirzepatide, 2.5-5mg mg weekly end up being used like Metformin for it’s longevity effects, probably because of how it helps insulin resistance. In other words, in future, folks will be using it not only to lose weight, but because of it’s other potential metabolic, cardioprotective, neuroprotective and immunoprotective effects. But like everything else, without making the concomitant lifestyle changes, in particular, eating a high protein, low carb diet, doing resistance training and probably time restricted eating, the chances of it being effective are much less.