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The New Diabetes Drugs: Your best shot for weight loss?

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It almost sounds too good to be true, but there are drugs originally developed for type 2 diabetes that can lead to dramatic weight loss with few side effects. These drugs, called incretin mimetics, can help individuals shed up to 20% of their body weight - more than other anti-obesity drugs - while also improving blood pressure and cholesterol levels.

One of the most popular of these drugs is semaglutide, but high demand has led to shortages of some formulations. Additionally, these medications are expensive, costing between $1,000 and $1,500 per month and not covered by Medicare for obesity (although some private insurers may cover them). Individuals who might benefit from these drugs, and what else should they know about them?

What is Semaglutide?

Semaglutide is a type of medication called a glucagon-like peptide-1 (GLP-1) receptor agonist. GLP-1 is a hormone that helps regulate blood sugar levels by stimulating the production of insulin and suppressing the production of glucagon, another hormone that raises blood sugar levels. By acting as a GLP-1 receptor agonist, semaglutide helps to mimic the effects of GLP-1, resulting in lower blood sugar levels.

Benefits of Semaglutide

The benefits of semaglutide are numerous. For those with type 2 diabetes, it can help to improve blood sugar control, reduce the risk of cardiovascular events, and promote weight loss. For those struggling with obesity, semaglutide can help to reduce body weight and improve metabolic health markers. In addition, semaglutide has also been shown to have a positive impact on non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnea.

Side Effects of Semaglutide

Like all medications, semaglutide does come with the risk of side effects. Some of the most common side effects of semaglutide include nausea, vomiting, diarrhea, constipation, abdominal pain, and decreased appetite. These side effects are usually mild to moderate in severity and tend to improve over time. However, in rare cases, semaglutide can also cause more serious side effects, such as pancreatitis or thyroid cancer.

Dosage of Semaglutide

The dosage of semaglutide will depend on several factors, including the individual's medical history, weight, and overall health. Semaglutide is available as a once-weekly injection, which can be self-administered at home. The initial dose is typically 0.25 mg per week, which is gradually increased over several weeks to a maintenance dose of 1 mg per week. For those using semaglutide for weight loss, the dosage may be higher, up to 2.4 mg per week.

Anti-obesity and diabetes medications

The venom of Gila monsters, poisonous lizards that can maintain stable blood sugar levels even without food, inspired the development of exenatide (Byetta), the first incretin mimetic drug.

Today, there are more potent drugs that mimic GLP-1, including injectable medications such as dulaglutide (Trulicity), liraglutide (Victoza), and semaglutide (Ozempic), which is also available as a pill known as Rybelsus. Liraglutide and semaglutide are approved for weight loss in formulations marketed as Saxenda and Wegovy, respectively.

The latest addition to this group of drugs combines GLP-1 with another incretin mimic, GIP. Tirzepatide (Mounjaro) was approved for treating type 2 diabetes in May 2022 and is expected to be approved for the treatment of obesity by accelerated review in 2023.

Overlapping risks

Obesity, which now affects over 40% of Americans, is closely linked to both diabetes and cardiovascular disease, with up to half of new-onset diabetes cases in the US associated with obesity. According to Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Harvard-affiliated Brigham and Women’s Hospital, many cardiologists recognize that treating obesity is the best way to treat heart disease.

While other anti-obesity drugs may only result in modest weight loss of 5-8%, incretin mimetics, which imitate natural hormones produced by the gut and brain, can have multiple effects. They stimulate insulin release by the pancreas, slow down stomach emptying, and target brain receptors involved in reducing appetite.

The latest incretin mimetics, tirzepatide and semaglutide, can lead to significant weight loss and reduce HbA1c levels (a three-month average blood sugar measure) by up to two percentage points. Dr. Apovian notes that studies show semaglutide and liraglutide, an older drug, can also lower the risk of serious cardiovascular problems, such as heart attack and stroke, in people with obesity and diabetes. Currently, a large trial is underway to determine whether semaglutide reduces heart-related risks in overweight or obese individuals without diabetes.

Who might consider these drugs?

According to Dr. Apovian, individuals with diabetes and excess weight are suitable candidates for semaglutide or tirzepatide, particularly those with a high risk of heart disease. For those without diabetes, the same official standards for other anti-obesity drugs apply: a BMI of 30 or higher, or a BMI of 27 or higher with at least one weight-related health problem, such as high blood pressure or high cholesterol. You can use the calculator at /bmi-calculator to estimate your BMI.

Administering these drugs involves using a pen-like device with a tiny needle, similar to injecting insulin, in the abdomen or thigh. Common side effects include nausea, diarrhea, and constipation, which typically last no more than a week if you gradually increase the dosage while being supervised by an experienced doctor, Dr. Apovian explains.

If you discontinue taking the drug, you are likely to regain weight, which is similar to what would happen if you stopped taking blood pressure medication and your blood pressure increased. "Obesity is a disease, and we need to treat it like one," emphasizes Dr. Apovian.

Caroline Buckee

Caroline Flannigan is an epidemiologist. She is an Associate Professor of Epidemiology and is the Associate Director of the Center for Communicable Disease Dynamics.

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