Anti-obesity drugs: how they differ, how they work and how effective they are

To treat obesity, it is usually recommended to change lifestyle, reduce calorie intake, and increase physical activity. However, reducing obesity through lifestyle changes, increased nutrition and physical activity is one way. Another way that seems to realize the slogan “I eat and lose weight” is medication. Popular magazines and scientific articles are writing about the end of the obesity epidemic, which they attribute to the latest drugs. New drugs have revolutionized the treatment of the obesity epidemic. It is claimed that their effect on the treatment of obesity is similar to one of the most radical measures to overcome this disease – bariatric (obesity) surgery.

Medicines appeared recently, but now there are quite a lot of them on the market and under different names. Let’s clear up the confusion of their names and their purpose.

Semaglutide. Relatively recently – in 2017 The FDA approved a drug for the treatment of type 2 diabetes, the active ingredient of which was semaglutide. The drug is produced by the Danish pharmaceutical company Novo Nordisk. It comes in two forms – legal and edible. It quickly became clear that these drugs had effects beyond glucose control, one of which was a beneficial effect on the obese. in 2021 The US Food and Drug Administration (FDA) has approved a drug with the active ingredient semaglutide for adult weight control in obese adults. The medicine was intended for people who were obese and had at least one obesity-related health problem (such as high blood pressure).

What is the difference between drugs approved in Denmark and in the US? In principle, there is no difference, only the amounts of use differ – the one approved by the FDA can be used more. In addition, those taking this medicine are recommended to follow a diet and increase physical activity. The Danish manufacturer’s edible drug is less effective than the one approved by the FDA, so the Danish manufacturer’s drug is not approved for the treatment of obesity.

In 2024, the FDA expanded the use of an edible drug from a Danish manufacturer, whose active ingredient is semaglutide, and approved it for the treatment of cardiovascular disease (CVD) in obese individuals. The drug is now the first weight-loss drug to be approved for adults with obesity and CVD.

Tirzepatide. Medicines with the active ingredient tirzepatide were approved in the United States and other countries in 2022 for the treatment of type 2 diabetes. But they proved to be so effective in treating obesity that in 2023 the FDA approved the active substance tirezepatide as an obesity medicine.

Liraglutide. Medicines containing the active ingredient liraglutide, one for the treatment of type 2 diabetes and another for obesity, were approved in 2009 (EU), 2010 (US). Although their mechanism of action is the same as other drugs in this group, they are less effective than semaglutide drugs in reducing obesity. Semaglutide drugs are more than twice as effective against obesity as liraglutide.

The most popular drugs for type 2 diabetes and obesity are semaglutide and tirzepatide active ingredients. They are both similar in that they mimic the hormones released after a meal. However, their mechanism of action is not the same.

Semaglutide is a GLP-1 (glucagon-like peptide) receptor agonist. It mimics the effects of the hormone GLP-1, which is naturally released after a meal. The effect of GLP-1, naturally released in the gut after a meal, is twofold: it increases insulin (a hormone that lowers blood glucose) and inhibits the effects of glucagon (a hormone that increases blood glucose). When GLP-1 is naturally released in the body, its effects are short-lived (2-4 minutes). The effect of drugs whose active ingredient is GLP-1 agonists lasts up to 5 days. These drugs not only lower blood glucose levels, but also affect the brain (signaling the brain to stop eating), increase satiety, and slow down emptying of the stomach and intestines. This stops overeating, the person feels full for a longer time. So, in addition to treating type 2 diabetes, these drugs help you eat less food and reduce obesity.

Tirzepatide has a dual effect: in addition to the already described GLP-1 receptor agonist effects, it binds to receptors normally activated by glucose-dependent insulinotropic polypeptide (GIP) hormones. GIP not only increases the release of insulin, affects the areas of the brain that reduce appetite and the desire to eat, but also regulates the consumption and storage of calories in the body.

Although GLP-1 and GIP have slightly different modes of action, their clinical effects overlap, including satiety, slowing gastric emptying, increasing insulin release and insulin sensitivity, reducing glucagon, and, of course, reducing high glucose levels.

Taking medication definitely reduces obesity. Obese patients taking semaglutide lost 15 percent of their weight. in 68 weeks (Wilding et al., 2021; Garvey et al., 2022). This weight loss was achieved because subjects consumed fewer calories due to changes in hunger and satiety (Wilding et al., 2021).

In another study, obese subjects received 5 mg, 10 mg, 15 mg of tirzepatide per week for 72 weeks. Weight loss was 15, 19 and 21 percent (according to the amount consumed) (Jastrebof et al., 2022). Regardless of the significant weight loss achieved, the weight returns after stopping the medication. Obese subjects who received 2.4 mg (maximum dose) of semaglutide at week 68 lost weight but regained two-thirds of the weight after one year (Wilding et al., 2022).

Recent studies (Jensen et al., 2024) suggest that if drug treatment is combined with increased physical activity and diet, weight loss is maintained for at least a year without medication. Side effects of drugs are mainly related to gastrointestinal disorders such as: nausea, nausea, diarrhea, constipation, vomiting. In order to reduce or avoid side effects, which usually appear only after starting to take medication, it is recommended to start with lower doses and gradually increase them. People without type 2 diabetes are also at risk of pancreatitis (inflammation of the pancreas).

Diet and healthy lifestyle-based methods should be the main tools for obesity prevention and treatment. However, diet and exercise have so far proven to be effective long-term for only about 10 percent of obese people. For most people with severe obesity, these tips are not generally effective. Their only option until now was bariatric surgery. But should overweight people take the medication?

Arguments “in favor” of drugs: drugs definitely reduce obesity, they have a positive effect not only on type 2 diabetes but also on cardiometabolic indicators. Pros of drugs: They have side effects, weight loss comes back, they are prescription drugs, and they are expensive.

A recent article in the Journal of the American Medical Association states, “Treatment of obesity with GLP-1 agonists must be combined with long-term lifestyle modification.