Is Ozempic really a miracle weight loss drug?
We’re inside the Ozempic bubble right now. The hype around the GLP1 medications is at an all-time high, with most Americans having heard of this class of weight loss drugs and a large percentage currently or recently taking them. The frenzy in the media, healthcare community, and public discourse is unlike anything I’ve personally seen for a weight loss drug or treatment in my professional career. It’s overwhelmingly positive, singing the praises of the new “miracle weight loss drug” we’ve all been waiting for.
I completely understand being intrigued and excited about the GLP1s – it makes sense given the dialogue around weight, health, and beauty standards in our culture. You might know someone who’s recently lost weight on one of the drugs, or you’re being encouraged to try one yourself from family or medical providers. I have had many a conversation with my clients who want to cut through the hype and develop a real understanding of the drugs. They’re hearing the GLP1s described as “miracle drugs” but also hearing about downsides like gastrointestinal distress, mental health disturbances, pancreatitis, and loss of muscle mass. Not to mention the concerns of cost, insurance coverage lapses, shortages fueling a market of now-illegally compounded versions of the drugs not approved by the FDA, and the fact that the GLP1s are meant to be used for life (this last concern often gets dismissed by healthcare providers but I think this really gets people because, other than bariatric surgery, weight loss interventions are rarely marketed as lifetime treatment). While the media and most of the medical community acknowledge the downsides, they’re often minimized and portrayed as “worth it” to enjoy the benefits of weight loss.
A person’s choice to try a GLP1 will never be met with judgement or disappointment from me. I will always support and prioritize bodily autonomy and a person’s right to choose to take a medication if they think it’s best for them. AND. I want you to feel empowered to make a fully informed choice for your health. To do that, it’s imperative you have the chance to consider with a healthy dose of skepticism all the available information. Let’s dive in…
What are the drugs known as “GLP1”s and how to they work (feel free to skip this section if you’re already aware of the drugs’ origins and mechanisms of action)?
“GLP1s” (or simply, “Ozempic”) is shorthand for the class of drugs called glucagon-like-peptide-1 receptor agonists (GLP1 RAs). They’re synthesized* to mimic the effects of the naturally occurring human hormone GLP-1. There are a bunch of these drugs currently on the market, but the ones getting all the attention lately are semaglutide and tirzepatide. Semaglutide is the generic name for Ozempic and Wegovy (same drugs, different FDA-approved uses and dosages), and is patented by the drug company Novo Nordisk. Tirzepatide is the generic name for Mounjaro and Zepbound,** and is patented by Eli Lilly. Earlier iterations of the drugs include liraglutide (Victoza and Saxenda) and dulaglutide (Trulicity). GLP1-RAs entered the scene 20 years ago, and were originally studied and approved for treating type 2 diabetes. Some of the later ones showed significant weight loss in study trials, and so have been more recently approved for weight loss in non-diabetic patients (starting around 2014 with Saxenda).
Like I mentioned, GLP-1 hormone is a naturally occurring gut hormone in humans. Its primary function is in regulating glucose metabolism and energy balance, and it’s released in response to a meal. It has receptors in the pancreas, gastrointestinal (GI) tract, and brain, allowing it to exert its functions in those organs:
Pancreas - enhances the secretion of insulin in response to rising blood sugar and inhibits glucagon (the hormone that rises when blood sugar levels reach a low point, typically several hours after a meal, to stimulate the liver to break down and release stored glucose to keep blood sugar levels stable)
GI tract – slows down the emptying of the stomach so food stays in the stomach longer, leading to feeling fuller sooner, and for longer, on less food
Brain – involved in reward pathways affecting appetite and desire for food
Think about taking a drug that mimics a hormone as if you are supplementing that hormone, like you might take a dose of vitamin C in a pill form entering cold and flu season to go above and beyond your normal intake. You’re adding more GLP1 to the mix, so its effects will be more pronounced than if you were relying solely on your naturally occurring GLP1 levels. What’s more, our natural GLP1 is mostly degraded before leaving the gut to enter circulation, whereas the GLP1 RA drugs are injectables, so will linger at higher levels in circulation for days. The net impact is the natural GLP1 effects on overdrive: reduced appetite, feeling fuller for longer on much less food, and less hedonic drive for food (you don’t want to eat, nothing sounds good, maybe even feel a little repulsed by food). All three of these effects could reasonably lead to substantial weight loss seen in trials of the drugs.
What are the pros, and what are the concerns?
Those who operate within a weight-centric model of healthcare and believe obesity is a disease and that weight loss interventions are primary paths toward improved health (which isn’t my view) are very excited about seeing the results in GLP1 RA trials. If you are comparing the weight loss outcomes in clinical trials of semaglutide and tirzepatide to any other weight loss intervention (except bariatric surgery), it’s clear that the drugs come out ahead by quite a bit – between 15-20% weight loss over the course of a year with the GLP1-RAs (1,2) vs. anywhere from 2-10% for most other medical and behavioral weight loss interventions. One caveat – the main body of research commonly cited to demonstrate the effectiveness of semaglutide and tirzepatide for weight loss are the randomized controlled trials funded by the drugs’ manufacturers (Novo Nordisk and Eli Lilly, respectively). That’s not to say they’re completely invalid, but it’s something to keep in mind to mitigate hype. Industry-sponsored trials still follow the scientific method, but there’s an obvious bias toward wanting the study to show their drug works. The studies are often designed to maximize the potential of the desired outcome and the groups of participants recruited don’t necessarily mimic real-world populations who would be taking the drugs. In fact, a recently published narrative review aimed to explore real-world outcomes and found weight loss effects significantly muted compared to drug company trials, likely due to high discontinuation rates due to adverse side effects, costs, and accessibility and coverage changes, and the fact that weight loss seems to be much less dramatic in folks with type 2 diabetes taking the drugs (3).
Biomarkers for metabolic health like liver function tests and cholesterol levels seem to be improving in GLP1 RA trials (as is seen in many weight loss intervention trials). Trials show that quality of life measures improve as well, and that doesn’t surprise me given that we live in a society where living in a higher weight body is stigmatized and not accommodated for (think about seating in medical offices and concert halls, clothing store options, and the fact that overt prejudice against higher-weight individuals is still socially acceptable).
As a weight-inclusive provider, I see these results through a more nuanced lens. I’ve poked a lot of holes in the weight centric model of healthcare in a previous post, and so I tend not to view weight loss outcomes alone as very meaningful in overall health and well-being. I believe that makes it easier for me to view the data skeptically and weigh pros and cons. And I do have a few major concerns regarding the harms these medications may be causing based on emerging evidence. We won’t have what I consider “long term” data for a while, but what we are already seeing worries me.
Side effects
The most well-known side effects of the GLP1s are the nausea, constipation, and overall GI distress that many people experience (and that leads to many people discontinuing the drugs entirely). Rarer but possible side effects also include gastroparesis or stomach paralysis, intestinal blockage, and pancreatitis. Another common effect is the loss of a sense of pleasure and comfort around food, which can contribute to feelings of sadness, anger, and frustration when trying to feed yourself on a daily basis, let alone enjoy parties, the holidays, nights out at new restaurants, etc. To someone who’s felt out of control around food, or who uses food in times of stress to numb their feelings, this might seem like a relief at first, but a life without enjoying food can bring with it a deep sense of grief.
Malnutrition
A drug that accentuates and perpetuates the effect of a hormone that produces less hunger, more fullness on smaller portions, and less pleasure obtained from food, AND causes GI disturbances will lead to eating significantly less food than the body needs to continue functioning at its metabolic equilibrium (meaning, there will be a drastic deficit in the amount of energy coming in compared to the amount being expended to support life). This will ultimately manifest as:
Nutrient deficiencies (not a lot of data yet but I’d bet it’s coming)
Metabolic adaptation (reduction in energy expenditure as a response to the threat of starvation from long-term under fueling)
Significant loss of “lean mass” - muscle mass and bone mass
Weight plateaus and weight regain
All of the above can and do happen at any body size. The body doesn’t know people are choosing this situation. The body will read it as a threat to survival and act accordingly to prevent starving to death. Research is already showing some of the above concerns are coming to fruition:
Body composition changes (significant loss of lean body mass): Novo Nordisk’s original trial on semaglutide (STEP1) included a subgroup of participants who underwent body composition analysis with dual-energy X-ray absorptiometry (DXA) to assess changes in body composition during the trial. They found that 40% of the weight loss these people experienced was loss of lean body mass (muscle plus bone) (1). These results are often dismissed because the overall composition change is seen as “favorable” since fat mass loss is also substantial. I am certain that’s not scientifically accurate – any substantial loss of lean mass (muscle and bone) is negative on its own, leading to increased risk of frailty, mobility issues, falls, infections and delayed wound healing (4), and fractures, not to mention day to day feeling less energy and more fatigue doing normal activities. Long term muscle loss (sarcopenia) and bone loss is already a concern in our aging population including especially post-menopausal women, a major target market for GLP1 RAs.
Metabolic adaptation and weight plateau and regain: There is a near-universal finding in weight loss intervention trials: an initial steep decline in weight outcomes at the start of the study period, with weight loss slowing, plateauing, and eventually reversing over the duration of the study (especially evident in studies over 1 year long). Any dieter will tell you this has been their personal experience as well. The GLP1 RA trials are so far turning out to follow that precedent. I can’t reproduce a table without permission, but if you open up the STEP1 trial article (1) and take a look at figure 1A, you’ll see what I am referring to. As far as I know there aren’t any studies on this yet but I wouldn’t be surprised if those who continue the injections past the 2 year mark eventually start to regain weight. Anecdotally, I’ve already heard a few people say this has been their experience. We won’t have that data set published for a few years. What we do know is that stopping the drugs does result in significant regain. Novo Nordisk published results from their trial showing that within 1 year of stopping semaglutide, participants regained 2/3 of the weight they’d lost in the first year being on the drug (5). Eli Lilly’s results showed similar levels of weight regain when participants stopped tirzepatide (6). Do a search on Reddit for “weight regain after stopping Ozempic” and you’ll see rebound weight gain is common. That tracks with what we know about the physiological response to starvation/energy restriction and what happens when that threat is removed – the body adapts by regaining lost weight, and a larger proportion of the regained weight is fat vs. muscle (this is protective, fat is a much better source of long-term fuel should we face another famine in the future).
Eating disorder risk:
Eating disorders are serious mental and physical conditions that can result in dangerous complications and have one of the highest mortality rates of any psychiatric illnesses (alongside substance use disorders). Eating disorders have a 9% lifetime prevalence risk in the US. Only 6% of people diagnosed with an eating disorder are medically “underweight” and in fact eating disorder risk is higher in those with higher BMIs. Dieting, the experience of weight stigma and body shaming are all know risk factors for eating disorders so it’s fair to assume that the anti-fat narrative fueling GLP1 use and the food restriction triggered by the effects of GLP1s could exacerbate an already-present eating disorder or increase the risk of a vulnerable person developing a restrictive eating disorder. Praise for weight loss will reinforce eating disorder cognitions, and future weight plateau or regain can cause marked psychological distress, potentially triggering dangerous eating disorder behaviors. We don’t yet have long term data on the impact of the GLP1s on eating disorders or overall psychological well being. In my opinion, the short term studies that have been done so far showing that GLP1 use “improved” binge eating disorder (8) need to be held in nuanced context. The GLP1s are suppressing appetite and impacting the pleasure aspect of food but not addressing the underlying psychological causes of bingeing, while actually reinforcing the physiological triggers for bingeing (food restriction/deprivation). In terms of long term eating disorder healing and recovery, this is probably a recipe for disaster.
A few other concerns:
Long-term safety: pretty self-explanatory, we just don’t know yet.
The cost: Semaglutide and tirzepatide are currently under patent so we won’t see generics in the US for another 7-8 years and 11-13 years, respectively (although patents in China for Ozempic expire in 2026 and there are already several generics in testing right now) (9). Directly self-paying for GLP1s from the respective drug companies will run you about $350-500/month; pharmacy prices vary and can be much higher. Many insurance plans will not cover them for weight loss (but will cover them for diabetes, at the doses approved to treat diabetes). In gathering info for this post I came across this line in a NY Times article from 2023 that stopped me in my tracks: “In the past few weeks, Novo Nordisk’s market value has exceeded the size of the Danish economy.” (10) (Novo is a Danish company). While I’m not surprised a weight loss drug had this power, it’s kind of wild to read that. This didn’t last however, due to Eli Lilly’s Zepbound prescriptions rising past Wegovy’s. Novo’s stock dropped this year and they recently announced they’re laying off 11.5% of their work force. Eli Lilly is now the most valuable drug company in the world, and is planning to build 4 new manufacturing facilities in the US (a pill form of GLP1s is in the pipeline).
Accessibility and the continued use of compounded versions: During the shortages of semaglutide and tirzepatide last year the FDA allowed “emergency” use of compounded versions of the GLP1s which carry safety and efficacy concerns. There are definitely reputable compounding pharmacies out there, but there are also definitely shady ones. The shortage is over and the FDA has ordered the restriction of these compounded GLP1s but they’re still being sold and used (11). And while currently the drugs are not in shortage, the fact that they were in the past could indicate future problems with accessing them. This could lead to treatment disruptions for people using them for diabetes, as well as resulting weight cycling, the harms of which were recently explored in a study that weight science speaker and writer Ragen Chastain broke down in her Substack newsletter (12).
To return to our original inquiry: are the GLP1s the long-awaited weight loss miracle drugs? Perhaps it depends on how you define “miracle drug”, which is completely up to you. Maybe my standards are high, but I tend to think a “miracle weight loss drug” would have to bypass the metabolic adaptation response to produce life-long weight loss maintenance (no regain, no weight cycling) without any of these adverse effects (no GI disturbances, a healthy appetite and desire to eat enough food, no nutritional deficiencies, minimal effect on lean body mass). In our weight-obsessed culture, the GLP1 excitement is understandable. If you’ve been curious about these medications, I hope this post offers you some clarity and you feel empowered to make the choice that makes the most sense to you.
Footnotes:
*Fun fact: the inspiration for GLP1s came from a lizard native to the Southwestern US and Northwest Mexico called the Gila monster. Researchers discovered that a compound in the Gila’s venom called exendin-4 looked similar to the human form of the GLP1 hormone, but lasted in the body much longer. The first GLP1- RA, exenatide (released in 2005 under the brand name Byetta), was synthesized using exendin-4 as a blueprint.
**Tirzepatide is actually a combination of 2 hormone mimetics – GLP1-RA and GIP-RA (gastric inhibitory peptide receptor agonist).
Citations:
STEP 1 trial of semaglutide: https://www.nejm.org/doi/10.1056/NEJMoa2032183
SURMOUNT-1 trial of tirzepatide: https://www.nejm.org/doi/10.1056/NEJMoa2206038
Real-world outcomes of GLP1s: https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.16364
Muscle loss with GLP1s: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00272-9/abstract
Weight regain after semaglutide withdrawal: https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.14725
Weight regain after tirzepatide withdrawal: https://jamanetwork.com/journals/jama/fullarticle/2812936
Eating disorder stats: https://anad.org/eating-disorder-statistic/#general
GLP1s and binge eating disorder review: https://link.springer.com/article/10.1007/s40519-025-01720-9
Ozempic patent landscape: https://journals.library.columbia.edu/index.php/stlr/blog/view/653
NY Times piece on Novo Nordisk’s impact on Danish economy: https://www.nytimes.com/2023/08/28/business/denmark-ozempic-wegovy.html
GLP1 shortage over, compounding now restricted: https://www.pharmacytimes.com/view/out-of-shortage-into-controversy-the-fight-over-glp-1-compounding
Ragen Chastain’s breakdown of weight cycling study: https://weightandhealthcare.substack.com/p/new-study-of-harms-of-weight-cycling