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The global obesity epidemic and its effect on public health

The rate of obesity worldwide has almost tripled since 1975, leading to a global epidemic of obesity and overweight. As of 2016, reportedly 39% of adults around the world are overweight, and 13% have obesity. In the United States alone, more than 2 in 5 adults are affected by obesity and nearly 1 in 3 are overweight. The obesity epidemic has serious consequences for public health, as obesity and overweight are associated with an increased risk for diabetes, stroke, heart disease, and certain cancers.

Obesity is most commonly treated with changes in lifestyle like increasing physical activity and reducing calorie intake. In addition, for some individuals, weight-loss medications or surgery may be considered.

Which diabetes drugs can be used for chronic weight management?

Glucagon-like peptide 1 (GLP-1) receptor agonists are a class of drugs that help reduce blood sugar and have been used in Type 2 diabetes treatment programs. However, GLP-1 receptor agonists also promote weight loss.

Therefore, the GLP-1 receptor agonists Wegovy® (semaglutide) and Saxenda® (liraglutide) have been approved by the United States Food and Drug Administration (FDA) as a part of chronic weight management programs for individuals with obesity or who are overweight and experiencing a weight-related health issue. Semaglutide is also the active component of other pharmaceutical drugs like Ozempic® and Rybelsus®. As of February 2024, Ozempic® and Rybelsus® have not been approved by the FDA for weight management but are sometimes prescribed off-label for this indication by healthcare providers.

The dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist Zepbound® (tirzepatide) has also been approved by the FDA as a component of chronic weight management programs for individuals with obesity or those who are overweight and experiencing a weight-related health issue. When used for Type 2 diabetes, tirzepatide is prescribed under the brand name Mounjaro®.

GLP-1 receptor agonists can only be administered after being prescribed by a qualified healthcare professional. Most of them are used as injections in the fatty tissue under the skin (subcutaneously), except for Rybelsus®, which is manufactured in a tablet form. To maintain their effect on weight, GLP-1 receptor agonists are typically taken long-term.

How these drugs work for diabetes and why they work for weight loss

GLP-1 receptor agonists mimic the effect of the hormone GLP-1, which is naturally released in the small intestine after eating. In patients with diabetes, GLP-1 receptor agonists are thought to work by promoting the release of insulin and inhibiting the release of glucagon, which helps to reduce blood sugar levels and keep them under control.

GLP-1 receptor agonists also promote weight loss by slowing the movement of food from the stomach into the small intestine and interacting with areas of the brain that regulate the sense of hunger and the feeling of fullness after eating (satiety). Overall, they have been shown to suppress appetite and promote the feeling of satiety, helping to reduce the number of calories consumed.

In addition to its effect on the GLP-1 receptor, Zepbound® activates the GIP receptor, which also suppresses appetite.

Can side effects occur?

If side effects occur, they are most commonly gastrointestinal and may include constipation or diarrhea, abdominal pain, nausea, vomiting, upset stomach, bloating or gas. Other commonly reported side effects are headache and tiredness. GLP-1 receptor agonists are not recommended for those with a history of inflammation of the pancreas (pancreatitis) or a family history of certain thyroid cancers. In patients with uncontrolled diabetes, there is a risk of worsening disease of the retina (retinopathy).

When deciding whether to prescribe you a GLP-1 receptor agonist for you, your healthcare provider will consider any other medications you are taking or medical conditions you have.

Current drug shortages

Since GLP-1 receptor agonists have been found to help people lose weight, the demand for them has increased dramatically. Manufacturers have not been able to boost production sufficiently to keep up with the elevated demand, leading to drug shortages. This has negatively impacted many patients with diabetes, who have experienced difficulties filling their prescriptions. As of February 2024, shortages of semaglutide, tirzepatide, and liraglutide injections continue to be reported.

Insurance coverage issues

The use of GLP-1 receptor agonists for the treatment of obesity is often not reimbursed by insurers. However, without insurance coverage, the out-of-pocket cost of GLP-1 receptor agonists may reach or even exceed $15,000 per year, which may restrict patient access to them. Several approaches may help to make these drugs more affordable, including the use of manufacturer coupons, a prescription discount card, a flexible spending account, a health spending account or enrollment into a drug assistance program.

What to ask your doctor if you are considering a GLP-1 receptor agonist

GLP-1 receptor agonists should only be taken if prescribed by a qualified healthcare professional. If you have obesity or are overweight, have or wish to avoid or minimize health conditions related to excess weight, and you wonder whether a GLP-1 receptor agonist should be a part of your weight management plan, talk to your healthcare provider. Together, you can discuss the benefits and risks of GLP-1 receptor agonists and whether they are right for you.

New treatments that are under development

Novel GLP-1 receptor agonists for oral administration are being developed and are expected to be available at a lower cost than injectable drugs. In addition, other classes of diabetes drugs, such as sodium glucose cotransporter 2 (SGLT-2) inhibitors, are also being investigated for their potential to promote weight loss.