Research Roundup #42: Is This Weight Loss Drug Actually Safe and Effective? | Legion
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An increasing number of people are using drugs to lose weight.
It’s clear why, too.
Weight-loss medications were once viewed as unproductive and potentially dangerous, but studies apparently now show that they’re highly effective.
Take the antidiabetic-cum-weight-loss drug semaglutide, known by its brand names Ozempic, Wegovy, and Rybelsus.
In a study conducted by scientists at the University of Liverpool, researchers asked 1,961 overweight or obese people to reduce their calorie intake by ~500 calories per day, increase their physical activity, and take either 2.4 mg of semaglutide or a placebo once weekly for 68 weeks.
The results showed that those who took semaglutide improved their weight (–34 lb. vs. –6 lb.), waistline measurements (−5.3” vs. −1.6”), blood pressure, blood sugar, cholesterol, and inflammation levels, and physical and mental function significantly more than those who took a placebo.
Researchers from the University of Alabama at Birmingham reported almost identical findings in a subsequent 2-year study on semaglutide, too.
In other words, studies suggest that semaglutide is almost as effective as bariatric surgery at boosting weight loss and health. The upside is you don’t need an operation to get the benefits.
Is taking semaglutide the best way to lose weight, then?
There are a few reasons I think not.
Semaglutide affects hormones in your gut and brain to make eating less appealing. So long as you’re taking it, you won’t feel like eating as much as usual, and you’ll likely lose weight as a result.
When you stop taking it, however, your appetite will normalize, and if you haven’t altered how you approach dieting and exercise, any weight you lost while using semaglutide will likely return.
By making eating undesirable, semaglutide also makes it difficult to consume enough daily protein, which is one reason semaglutide users tend to lose a lot of muscle.
For instance, in the study by the University of Liverpool, almost 45% of the weight each semaglutide user lost was muscle, and in a study conducted by scientists at the University of Dundee, diabetics taking semaglutide lost ~13 lb. of body weight, of which ~40% was muscle.
This is significant because maintaining muscle is paramount for good health: It decreases your risk of disease, helps you avoid injuries, and boosts longevity. In other words, semaglutide ramps up weight loss, but it does so in a way that’ll likely hinder your health over time.
You can help mitigate this by lifting weights, but you’ll still probably lose some muscle unless you eat enough protein.
Another reason to be chary of semaglutide is its safety.
Most who take semaglutide experience gastrointestinal issues, including nausea, vomiting, stomach pain, diarrhea, and constipation, though these often diminish with continued use.
And while many experts believe the risks are minimal, some research has linked semaglutide use with an increased risk of thyroid cancer, pancreatitis, diabetic retinopathy, and gallbladder disease.
All of this said, semaglutide may still make sense for some people.
If your health demands that you rapidly lose weight, taking semaglutide is a viable solution. However, if you’re overweight or obese but unlikely to suffer any imminent ill health or simply want to lose weight to look and feel better, there are healthier ways to do it.
Specifically, you need to eat 20-to-25% fewer calories than you burn every day, get about 40% of your daily calories from protein, and do 3-to-5 strength training workouts weekly.
This approach isn’t as easy as injecting yourself with semaglutide every seven days. Still, it ensures you mostly lose fat and not muscle, comes with a wide range of other benefits, and gives you the best chance of maintaining a healthy body composition in the future.
If you want a diet and exercise plan designed to help you lose weight like clockwork and get fitter and healthier than ever, check out my fitness books for men and women, Bigger Leaner Stronger and Thinner Leaner Stronger.
Takeaway: Drugs like semaglutide can help you rapidly lose weight, but aren’t without consequences. If you want to lose fat and not muscle without experiencing side effects or regaining the weight you lose when you finish dieting, maintain a calorie deficit, eat a high-protein diet, and regularly exercise.
This article is part of our weekly Research Roundup series, which explores a scientific study on diet, exercise, supplementation, mindset, or lifestyle that will help you gain muscle and strength, lose fat, perform and feel better, live longer, and get and stay healthier.
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+ Scientific References
- Bleasdale, E. E., Thrower, S. N., & Petróczi, A. (2018). Would you use it with a seal of approval? Important attributes of 2,4-Dinitrophenol (2,4-DNP) as a hypothetical pharmaceutical product. Frontiers in Psychiatry, 9(APR), 124. https://doi.org/10.3389/FPSYT.2018.00124/FULL
- Holborow, A., Purnell, R. M., & Wong, J. F. (2016). Case Report: Beware the yellow slimming pill: fatal 2,4-dinitrophenol overdose. BMJ Case Reports, 2016. https://doi.org/10.1136/BCR-2016-214689
- Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., & Kushner, R. F. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine, 384(11), 989–1002. https://doi.org/10.1056/NEJMOA2032183
- Garvey, W. T., Batterham, R. L., Bhatta, M., Buscemi, S., Christensen, L. N., Frias, J. P., Jódar, E., Kandler, K., Rigas, G., Wadden, T. A., & Wharton, S. (2022). Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine, 28(10). https://doi.org/10.1038/S41591-022-02026-4
- Schauer, P. R., Bhatt, D. L., Kirwan, J. P., Wolski, K., Brethauer, S. A., Navaneethan, S. D., Aminian, A., Pothier, C. E., Kim, E. S. H., Nissen, S. E., & Kashyap, S. R. (2014). Bariatric surgery versus intensive medical therapy for diabetes–3-year outcomes. The New England Journal of Medicine, 370(21), 2002–2013. https://doi.org/10.1056/NEJMOA1401329
- Maciejewski, M. L., Arterburn, D. E., Van Scoyoc, L., Smith, V. A., Yancy, W. S., Weidenbacher, H. J., Livingston, E. H., & Olsen, M. K. (2016). Bariatric Surgery and Long-term Durability of Weight Loss. JAMA Surgery, 151(11), 1046–1055. https://doi.org/10.1001/JAMASURG.2016.2317
- Sjöström, L. (2013). Review of the key results from the Swedish Obese Subjects (SOS) trial – a prospective controlled intervention study of bariatric surgery. Journal of Internal Medicine, 273(3), 219–234. https://doi.org/10.1111/JOIM.12012
- Courcoulas, A. P., Christian, N. J., Belle, S. H., Berk, P. D., Flum, D. R., Garcia, L., Horlick, M., Kalarchian, M. A., King, W. C., Mitchell, J. E., Patterson, E. J., Pender, J. R., Pomp, A., Pories, W. J., Thirlby, R. C., Yanovski, S. Z., & Wolfe, B. M. (2013). Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. JAMA, 310(22), 2416–2425. https://doi.org/10.1001/JAMA.2013.280928
- Benraouane, F., & Litwin, S. E. (2011). Reductions in Cardiovascular Risk After Bariatric Surgery. Current Opinion in Cardiology, 26(6), 555. https://doi.org/10.1097/HCO.0B013E32834B7FC4
- Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M. L., Woo, V., Hansen, O., Holst, A. G., Pettersson, J., & Vilsbøll, T. (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine, 375(19), 1834–1844. https://doi.org/10.1056/NEJMOA1607141/SUPPL_FILE/NEJMOA1607141_DISCLOSURES.PDF
- Ronveaux, C. C., Tomé, D., & Raybould, H. E. (2015). Glucagon-Like Peptide 1 Interacts with Ghrelin and Leptin to Regulate Glucose Metabolism and Food Intake through Vagal Afferent Neuron Signaling. The Journal of Nutrition, 145(4), 672. https://doi.org/10.3945/JN.114.206029
- Goldenberg, R. M., & Steen, O. (2019). Semaglutide: Review and Place in Therapy for Adults With Type 2 Diabetes. Canadian Journal of Diabetes, 43(2), 136–145. https://doi.org/10.1016/j.jcjd.2018.05.008
- McCrimmon, R. J., Catarig, A. M., Frias, J. P., Lausvig, N. L., le Roux, C. W., Thielke, D., & Lingvay, I. (2020). Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised controlled clinical trial. Diabetologia, 63(3), 473–485. https://doi.org/10.1007/S00125-019-05065-8
- Kim, G., & Kim, J. H. (2020). Impact of Skeletal Muscle Mass on Metabolic Health. Endocrinology and Metabolism, 35(1), 1. https://doi.org/10.3803/ENM.2020.35.1.1
- McLeod, M., Breen, L., Hamilton, D. L., & Philp, A. (2016). Live strong and prosper: the importance of skeletal muscle strength for healthy ageing. Biogerontology, 17(3), 497. https://doi.org/10.1007/S10522-015-9631-7
- Smits, M. M., & Van Raalte, D. H. (2021). Safety of Semaglutide. Frontiers in Endocrinology, 12. https://doi.org/10.3389/FENDO.2021.645563
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