Semaglutide is one of the most effective weight loss drugs ever discovered by science. It is highly effective and belongs to the new class of drugs called GLP-1 agonists. This article will explore every aspect of using semaglutide for weight loss, from efficacy to safety and everything in between.
The drug has become a revolution in weight loss treatment. It is one of the most popular weight loss drugs. Its popularity is so great that its manufacturer is struggling to produce it in enough quantities. It is one of the biggest blockbuster drugs after the invention of Viagra.(1) It is now among the most in-demand drugs globally.
There are a few reasons why semaglutide is such a popular drug. It is among the most effective weight loss treatments. However, the second reason for its popularity is that more obese people are living in the world than ever. The world is now becoming an obese place. The US is the fattest country in the world, with 40% of people obese and another 30% overweight.(2) It means that less than one-third of individuals in the US have normal weight. The picture is similar in the EU, and obesity is even on the rise in developing nations.
Later in this article, we will discuss semaglutide in more detail. It is vital to understand that semaglutide is now a US FDA-approved weight loss remedy.(3) Thus, its use is not off-label, as quoted by some websites. Semaglutide is the drug’s chemical or international non-proprietary name (INN). Since it is also used to manage diabetes, it is sold under two brands, Ozempic and Wegovy. Ozempic is approved for diabetes treatment, and Wegovy is approved for diabetes treatment.(4,5) Since Ozempic and Wegovy both contain semaglutide, both are good for managing diabetes and obesity.
Although Ozempic and Wegovy are chemically the same and contain semaglutide, there is a minor difference between the two. It appears that semaglutide’s dosage in diabetes is lower than in obesity. Thus, Wegovy has a higher dosage of 2.4 mg (max. dose for diabetes control is 2 mg weekly).
Semaglutide is given subcutaneously or below the skin as a weekly dose, making its use quite comfortable in the long term. Such an injection is almost pain-free. Doctors would often start with a low dose and may increase the dose gradually to its most effective dosage, 2.4 mg.
So, all this means is that it is entirely legal and safe to use semaglutide for weight loss, and it is a medically approved remedy.
Why Use Medications for Obesity?
One of the questions that arise is why use medications for obesity. There has been an ongoing debate about whether obesity is a disease or just a behavioral disorder. Historically, doctors have seen obesity as a behavioral disorder, a condition that occurs due to certain habits or lifestyle choices.
However, over the years, the nature of obesity has changed. It occurs not only due to excessive calorie intake but also due to a sedentary lifestyle, stress, inflammation, hormonal issues, gut changes, alterations in the gut-brain axis, and more. Moreover, over the years, obesity has emerged as one of the leading causes of death since it increases the risk of heart attack, stroke, mental health issues, brain disorders, respiratory conditions, joint disorders, and more. So, yes, obesity kills in the long run, and it also causes much disability.
Since obesity is so bad, doctors have finally started looking at obesity a bit differently. They do not consider it as a mere risk factor. The US has become the first nation to classify diabetes as a disease and not merely a risk for other health conditions.(6)
The classification of obesity as a disease by the American Medical Association (AMA) has been a game changer. Since science recognized obesity as a disease, this fueled research into the topic as medical science is more interested in studying diseases. However, this decision has had an even greater impact. Diseases must be actively treated, and this means that obesity must be treated just like any other health issue. This has led to increased research, the introduction of new anti-obesity drugs, and the approval of semaglutide by the US FDA for obesity treatment.
Of course, no one says that one should solely rely on drugs for managing obesity. It is still a lifestyle disorder, and for the best effect, it is vital to combine medications with lifestyle disorders. However, medications can help significantly, especially considering many people cannot make sufficient lifestyle changes.
These days, BMI is the most widely accepted way of understanding whether or not one is living with obesity. BMI helps understand how much a person’s weight is relative to height. So, to calculate BMI, one needs two kinds of data: the height of the person and body weight. One can use online calculators to know one’s BMI.
If a BMI is above 30, one is obese. BMI of 25 to 30 is overweight, but not obesity. A BMI of above 40 means gross obesity requiring urgent medical treatment, and it even justifies surgical treatment. Ideally, people should keep their BMI below 25. However, only one-third of Americans have a BMI of 25 or less. About half of all US adults can benefit from medical treatment of obesity. This underlines the importance of understanding semaglutide.
How Semaglutide Work?
Of course, semaglutide is not the first anti-obesity drug. It is also not the first anti-diabetes drug shown to help with weight loss. However, it is the first GLP-agonist approved for weight loss. It is definitely a drug that changed the way doctors treat obesity.
Earlier approaches for managing body weight through medications focused on either the brain, thus modulating appetite, or altered absorption of nutrients. Therefore, for example, Qsymia mainly reduced appetite, and Orlistat reduced absorption of fats.(7) However, these treatment approaches had limitations like many side effects and limited efficacy. Often, people develop tolerance to these medications on prolonged use.
Doctors have also been using anti-diabetes drugs as off-label obesity treatment for a long. Thus, one of the earliest anti-diabetic drugs, metformin, is known to improve insulin sensitivity and promote weight loss.
Type 2 diabetes (the most common diabetes type) and obesity have much in common. Moreover, type 2 diabetes is more likely to occur in obese patients. Hence, most oral drugs used to manage type 2 diabetes may cause weight loss. However, most drugs for managing diabetes cause only small weight loss.
Semaglutide has been a game-changer since it causes significant weight loss. Doctors saw such great weight loss with the drugs that they started using them extensively for managing obesity. This led to more medical research and, ultimately, the approval of the US FDA for obesity treatment.(3,7)
Semaglutide is not the first drug, but one of the most effective GLP-1 receptor agonists. What does that mean? Well, it appears that when people eat food, a hormone called incretin is released by the gut and increases insulin production by the pancreas. This increase in incretins occurs due to an activation of GLP-1 receptors found in the gut. Hence, medications that stimulate these receptors increase incretin production and, thus, insulin. However, incretins have other roles in the body and gut. They slow down gastric emptying and also play a vital role in satiety. Thus, GLP-1 agonists reduce appetite and make people feel full. Hence, these drugs promote weight loss.(8,9)
However, researchers have found that incretins have many other body functions, and these hormones play vital roles in numerous body functions. Semaglutide can also be seen as an incretin mimetic or a substance that increases incretin production by stimulating GLP-1 receptors. These receptors are present in the gut, brain, and other body parts, and science is still exploring their role in health and well-being. Therefore, it is pretty likely that semaglutide may find even more uses in the future.
For example, now new studies show that GLP-1 agonists like semaglutide can also lower inflammation, have a greater impact on the brain than imagined earlier, promote nerve growth, boost heart health, reduce fat deposition, boost endocrinal function, and may even lower the risk of certain tumors.(10)
What Does Science Say? – Clinical Evidence
When we say that semaglutide is a US FDA-approved obesity treatment, it means that the drug has passed extensive testing, and studies show that it is safe and effective. US FDA approved semaglutide in 2021. It is now clinically approved for managing obesity. Thus, anyone with a BMI above 30 or above can use semaglutide for weight loss. However, even overweight individuals can also use semaglutide if they have obesity-related ailments like high blood pressure, high levels of bad cholesterol, or other health issues.(3)
US FDA approved the maximum dose of 2.4 mg given weekly below the skin. The dosage of medication is increased gradually over 16-20 weeks to avoid gastrointestinal side effects. Increasing dosage slowly over several weeks gives the body enough time to adapt to the drug.
There have been many long-term studies showing that it is an excellent medication. Thus, a clinical trial using Wegovy/semaglutide for 68 weeks in 2600 patients found that it could help in most cases. In most of these studies, there were more women than men. The drug was many times more effective than placebo. Further, it can help reduce much greater body weight than exercise or dietary measures used alone.(3)
Of course, people might have some questions, like if it is for diabetes if it is safe for use in non-diabetics, and if it won’t reduce blood sugar levels in those without diabetes. What is impressive about semaglutide is that it normalizes insulin levels but does not increase insulin levels above normal levels. Thus, in those with normal insulin production and those living without insulin resistance, it does not cause side effects and does not increase insulin above the normal levels. Hence, it is entirely safe for use in non-diabetics. Not only that, studies show that it is even more effective for weight loss in non-diabetics!(11)
Since the studies show that it is even better for non-diabetics, answering questions like how that could be possible is vital. Well, the explanation is simple: those living with diabetes have significant insulin resistance, and they are living with severe metabolic disorders. Hence, medications for weight loss are less effective in such people. In individuals without diabetes but living with obesity, medications work better, as they are more sensitive to insulin, incretins, and other hormonal changes that occur by using these medications. Most importantly, using semaglutide for weight loss will also help prevent diabetes. Yes, it is an excellent choice for those living with obesity and prediabetes.
Yet, another common question people ask is what to expect when using these medications. How much weight loss can one expect? Well, there are many large-scale clinical studies that provide reliable data. Hence, it would be correct to say that most obese people can expect to reduce 10-15% of body weight in 16 weeks or 10 to 15 kg. More than 80% of people using these medications can expect to lose 5% or more weight in a year.(11)
Of course, there are significant individual differences in response to weight loss drugs like semaglutide. These differences are easy to explain. Medications are a helpful tool and not a replacement for lifestyle interventions. Although semaglutide would help even without other lifestyle interventions, one can experience much faster and better results by combining semaglutide with extensive lifestyle interventions like dietary measures and exercise.
It is also vital to note that semaglutide can help people carry out lifestyle interventions. For example, semaglutide can reduce appetite and thus help minimize food addiction. Similarly, it boosts insulin production in response to food intake, and thus, it can help people feel energized and gain lean mass.
Studies show that if combined with lifestyle interventions, it may work even at a lower dosage of 1.7 mg a week, which may be a safer option. Further, combining these with lifestyle interventions may help achieve faster results, such as losing 10% of the body weight in six months.(12)
Semaglutide and Safety
As the drug is meant for prolonged use, some may raise safety concerns. Semaglutide frequently causes side effects. However, these side effects are tolerable and short-lived. Most people develop tolerance to these side effects in a few weeks. Thus, side effects are rarely the reason for discontinuing the drug. Studies show that initially, about 75% would develop gastrointestinal side effects like bloating, abdominal pain, nausea, and vomiting. This happens as drugs slow down gastric emptying. However, within a few weeks, people become tolerant to the drug, meaning that these side effects are transitory and do not last for more than a few weeks.(11)
Since most side effects like stomach distress and nausea occur in the early stages, doctors would generally start semaglutide with a lower dosage. This provides patients enough time to get used to the drug. They would slowly increase the dosage every few weeks by keeping in mind how the patient’s body adapts to the drug.
Sure, there are a few other concerns, too. Some of the medications from this group have been shown to be bad for the pancreas and thyroid glands. However, studies did not show that semaglutide has these side effects. Nevertheless, one should only use semaglutide under medical supervision, as doctors or healthcare providers would keep a close eye on the person’s health.(13)
The Bottom Line
Researchers have long been looking for medications that could help manage obesity. Although many medicines were already approved, they were only moderately helpful. Moreover, older drugs failed to help in many instances. However, semaglutide is a game-changer for two reasons. Firstly, it can help lose body weight in significant amounts, that is 10% or more. Secondly, it is also relatively safe. Of course, it causes many side effects, but most of those side effects are tolerable and transient.
Semaglutide is so good for weight loss that it immediately became one of the most sought-after medical drugs. Initially, it was only approved for managing diabetes. However, soon, doctors realized that it is incredible for weight loss. Hence, doctors started its off-label use for managing obesity in different population groups. Soon, researchers found that it is also safe for prolonged use by those not living with diabetes. Ultimately, in 2021, the US FDA approved this drug for managing obesity so that people can use it with more confidence, and this will also ensure broader treatment availability with fewer legal limitations.
The drug is given weekly below the skin. Thus, it uses a very fine needle and does not cause pain, which is characteristic of intramuscular injectables. Subcutaneous injections are pretty easy to use. However, it is worth understanding that semaglutide is still a prescription drug. It causes few side effects. Hence, patients must be monitored, and the dosage requires regular corrections.
To sum up, this game-changer drug, semaglutide, provides hope to millions of adults living with obesity in the US. It is one of the most effective weight loss treatments. However, it is always good to combine semaglutide with lifestyle interventions like exercise and dietary measures for greater benefit. Lifestyle interventions will also ensure one does not regain weight after discontinuing the treatment.
References
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- Obesity Is Now A Disease, American Medical Association Decides [Internet]. 2013 [cited 2024 Mar 21]. Available from: https://www.medicalnewstoday.com/articles/262226
- National Institute of Diabetes and Digestive and Kidney Diseases [Internet]. [cited 2024 Mar 21]. Prescription Medications to Treat Overweight & Obesity – NIDDK. Available from: https://www.niddk.nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity
- Cf S, P K, R A. User’s guide to mechanism of action and clinical use of GLP-1 receptor agonists. Postgraduate medicine [Internet]. 2015 [cited 2024 Mar 21];127(8). Available from: https://pubmed.ncbi.nlm.nih.gov/26371721/
- Mahapatra MK, Karuppasamy M, Sahoo BM. Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Reviews in Endocrine & Metabolic Disorders. 2022;23(3):521.
- Zhao X, Wang M, Wen Z, Lu Z, Cui L, Fu C, et al. GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects. Front Endocrinol [Internet]. 2021 Aug 23 [cited 2024 Mar 21];12. Available from: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.721135/full
- Ojeniran M, Dube B, Paige A, Ton J, Lindblad AJ. Semaglutide for weight loss. Can Fam Physician. 2021 Nov;67(11):842.
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