People who need to lose weight may have heard of semaglutide, a medication that can be used to treat type 2 diabetes and is also effective for weight loss in obese individuals. Recently, a “weight loss version” of semaglutide aimed at improving obesity in adults was approved in China. This means that in the future, it can be marketed as a weight loss medication.
So, is it risky to use semaglutide, originally designed as a blood sugar-lowering drug, for weight loss? Can it be used in combination with the “blood sugar-lowering version” of semaglutide? How should we properly understand the weight loss effects of various weight loss medications? Let’s hear what Deputy Chief Pharmacist Zeng Weihua from Anshan Central Hospital in Liaoning Province has to say.
(1) Semaglutide is suitable for two types of obese populations
The cells of the ileum and colon in the body can secrete glucagon-like peptide-1 (GLP-1), which promotes insulin secretion in a glucose-dependent manner, regulating blood sugar levels. However, the natural GLP-1 secreted by the body is rapidly broken down and inactivated by dipeptidyl peptidase-4 (a protein) after entering the bloodstream, with a half-life of only 2 minutes. This is a normal mechanism in the body, and drugs can intervene in blood sugar regulation by utilizing this mechanism, with good safety.
As a synthetic GLP-1 analog, semaglutide can activate GLP-1 receptors in the body to regulate blood sugar, with a half-life of about 7 days, prolonging the effect of blood sugar regulation. Therefore, the original purpose of developing semaglutide was to treat diabetes.
Later on during clinical trials, researchers found that by activating GLP-1 receptors, semaglutide not only stimulates insulin secretion but also inhibits glucagon secretion, slows gastric emptying to increase satiety, and suppresses hypothalamic appetite centers. In other words, using semaglutide can reduce appetite, decrease food intake, and thus aid in weight loss.
Due to the clear weight loss effects of semaglutide, the United States approved its use for weight loss in non-diabetic adults in 2021, and China approved semaglutide for the treatment of adult obesity/overweight on June 25th this year.
Semaglutide has clear indications for weight loss. It mainly targets two groups of people: the first group consists of obese individuals with a body mass index (BMI) above 30, and the second group includes individuals with a BMI between 27 and 30 who also have one or more obesity-related comorbidities (such as hyperlipidemia, hypertension, obstructive sleep apnea, cardiovascular disease, etc.). Therefore, if your BMI is below 27 and you simply want to be slimmer because you’re unsatisfied with your figure, semaglutide is not suitable for you.
When semaglutide is used for weight loss, does it cause hypoglycemia? As a GLP-1 receptor agonist, the stimulatory effect of semaglutide on insulin secretion is glucose-dependent, meaning it significantly stimulates insulin release when blood glucose is high but does not stimulate insulin release when blood glucose levels normalize. Studies have shown that when blood glucose is below 4.5mmol/L, GLP-1 no longer promotes insulin secretion. Therefore, the risk of hypoglycemia from using semaglutide is very low.
Due to its effects on slowing gastric emptying and suppressing the hypothalamus, some people may experience gastrointestinal discomfort, dizziness, fatigue, nausea, diarrhea, vomiting, constipation, abdominal pain, indigestion, decreased appetite, and other adverse reactions after taking semaglutide. However, these adverse reactions are usually mild and tolerance increases with continued use. It is important to note that the initial dosage should not be too high, and the dosage should not be increased too quickly. Specific adjustments in dosage should be made under medical guidance.
Semaglutide also has some contraindications: allergic reactions to the medication, personal or family history of medullary thyroid carcinoma, individuals with type 2 multiple endocrine neoplasia syndrome, and pregnant women should not use the medication. In case of pancreatitis after taking the medication, prompt medical attention and immediate cessation of the medication are required. Most importantly, individuals under 18 years old are not recommended to use semaglutide.
(2) “Blood sugar-lowering version” and “weight loss version” cannot be interchanged
Semaglutide has both a “blood sugar-lowering version” and a “weight loss version.” How do they differ?
The semaglutide marketed as “Novo Nordisk” is used to treat diabetes, while the semaglutide marketed as “Novo Slim” is used for weight loss treatment. Both versions have the same main active ingredient, which works by activating GLP-1 receptors. However, pharmacists do not recommend switching between the two.
The “blood sugar-lowering version” of semaglutide comes in 2mg and 4mg doses. The recommended dosage starts at 0.25mg, to be injected once a week. After 4 weeks, the dosage is increased to 0.5mg, to be injected once a week. After treating with a 0.5mg dose for at least 4 weeks, the dosage can be increased to 1mg, to be injected once a week. The weekly dosage should not exceed 1mg.
The “weight loss version” of semaglutide comes in various doses such as 0.25mg, 0.5mg, 1mg, 1.7mg, and 2.4mg. It is also injected once a week, starting at 0.25mg, increasing the dose every 4 weeks until reaching the maximum weekly dose of 2.4mg. The dosage of semaglutide in the “weight loss version” is higher than that in the “blood sugar-lowering version.”
The difference between the two versions of semaglutide is not just the packaging. The “blood sugar-lowering version” requires long-term regular use with relatively fixed doses, with each vial of medication being used multiple times. The “weight loss version,” on the other hand, has single-dose packaging that allows for flexible adjustment of dosage based on changes in weight and tolerance to the medication.
In terms of cost-effectiveness, the “blood sugar-lowering version” of semaglutide is covered by medical insurance, so diabetic patients can benefit from insurance discounts. In contrast, the “weight loss version” of semaglutide is not covered by medical insurance, making the cost of the medication higher.
From a macro perspective, it is not recommended to use the “blood sugar-lowering version” of semaglutide for weight loss. This is not only because the specifications and dosages of the “blood sugar-lowering version” and the “weight loss version” of semaglutide vary, affecting the accuracy of medication use, but also because it could lead to competition for medical resources, causing potential drug supply shortages and even affecting the normal treatment of diabetic patients.
(3) Differences between semaglutide and the similar weight loss drug liraglutide
In addition to semaglutide, another well-known weight loss drug in recent years is liraglutide. These two drugs belong to the same pharmaceutical company. Liraglutide was approved for the treatment of diabetes in the United States in 2010, with the approval review report stating that besides lowering blood sugar, liraglutide also had potential benefits for weight loss. Following clinical trials, liraglutide was proven to safely and effectively reduce weight, leading to its approval for weight loss treatment in 2014, making it the world’s first GLP-1 agonist approved for weight loss treatment. In July 2023, domestically produced liraglutide for the treatment of obesity or overweight in China was also approved for marketing.
However, compared to the semaglutide with a half-life of about 7 days, liraglutide has a much shorter half-life of approximately 13 hours, requiring daily injections to maintain its effects, which could be less convenient. Thus, researchers improved liraglutide by developing semaglutide, which only requires a weekly injection while ensuring efficacy. Therefore, semaglutide can be considered as the “weekly formulation” of liraglutide.
Another difference is that liraglutide can only be administered by injection, while semaglutide is available in both injectable and oral formulations, greatly enhancing patient compliance with medication.
Comparing research results, semaglutide and liraglutide have similar rates of gastrointestinal adverse reactions and contraindications, but semaglutide has been shown to be more effective in treatment. However, semaglutide also has drawbacks, such as its higher price compared to liraglutide and limited production capacity, which may lead to supply shortages.
(4) Weight loss cannot rely solely on medication
From a medical perspective, obesity is a chronic complex disease caused by the interaction of biological, genetic, social, psychological, and environmental factors. As early as 1997, the World Health Organization defined obesity as a disease.
Obesity not only impairs the normal function of bodily tissues and organs but is also a contributing factor to various diseases, such as cardiovascular diseases, certain types of cancers, type 2 diabetes, etc. These diseases can reduce the quality of life of patients or shorten their life expectancy, with obesity being considered as the “root of all diseases.”
Obesity should be intervened in a timely manner, with active weight reduction efforts. However, weight loss cannot solely rely on medication because there is no perfect weight loss drug. While people may enjoy the benefits of medication, they also need to bear the risks of adverse reactions. Many unknown adverse reactions to drugs are only discovered through long-term observation after their market launch. For example, the weight loss drug “sibutramine,” which was launched in the United States in 1997, was once popular but was later found to carry serious cardiovascular risks and was banned in 2010.
Semaglutide was introduced in the United States in December 2017 and approved for weight loss treatment in June 2021. With less than 7 years as a blood sugar-lowering drug and just over 3 years as a weight loss drug, the duration for long-term safety observation of the drug is very short, and its long-term safety with continued use is still uncertain.
Moreover, excessive promotion of the weight loss effects of medications could lead to misunderstandings among the public: that unhealthy lifestyle consequences can be corrected with drugs. This is a wrong perception, so even if weight loss drugs have weight loss effects, they should not be used casually.
From the pharmacological analysis earlier, it should be clear that the reason semaglutide can contribute to weight loss is by “making one feel less hungry,” thereby reducing food intake. Controlling food intake can also be achieved by altering dietary structure and lifestyle habits. By arranging meal sequences properly, drinking soup before meals to induce satiety, consuming vegetables or low-sugar fruits next for their volume, low calories, and slow absorption rate to promote satiety, followed by consuming high-calorie meat dishes to further increase satiety, and ending with a small amount of staple food or carbohydrates to reduce overall calorie intake. People can also drink water before meals and consume a small amount of nuts (such as 10 almonds or 20 peanuts) before meals. Nuts containing unsaturated fatty acids can stimulate the secretion of cholecystokinin after eating, reducing appetite through both the vagus nerve and non-vagus nerve pathways.
Exercise is also one of the best methods to control weight. Aerobic exercise can reduce overall body fat, and it is recommended to engage in moderate-intensity aerobic exercise for at least 30 minutes daily, along with resistance strength training of at least 30 minutes, twice or more per week. Selecting appropriate exercise methods, intensities, environments, equipment, monitoring the effects at all times, can help prevent exercise injuries.
On the basis of adjusting diet and maintaining exercise, if weight is still difficult to control, it is recommended to seek medical advice. When necessary, under medical guidance, semaglutide or liraglutide can be used. For individuals with severe obesity (BMI≥32.5) or those with insignificant medication effects, metabolic surgery may be considered.
In conclusion, weight loss drugs are not the “lifesaving straw” for weight loss, so everyone must view the effects of medication rationally. The primary effort in weight control should still be to choose safe lifestyle interventions.
