semaglutide

semaglutide, drug used in the treatment of type 2 diabetes and to aid weight loss in persons who are severely overweight. Semaglutide was initially approved by the U.S. Food and Drug Administration (FDA) in 2017 to help control blood glucose levels in persons with type 2 diabetes; the drug was approved under the trade name Ozempic. In 2021 the FDA expanded the approval of semaglutide to include the treatment of persons who are obese or who are overweight and have a weight-related condition, such as hypertension (high blood pressure) or hypercholesterolemia (high cholesterol). As an anti-obesity treatment, the drug is marketed as Wegovy.

Mechanism of action

Semaglutide is classified as a glucagon-like peptide-1 (GLP-1) receptor agonist, meaning that it mimics the actions of GLP-1 hormone. GLP-1 is released in response to eating, at which time it enters the gut, causing delays in gastric emptying and inducing a feeling of fullness. GLP-1 activity moreover increases production of the hormone insulin, which helps regulate glucose homeostasis. In higher amounts, GLP-1 interacts with receptors in the brain involved in the regulation of appetite, thereby triggering a reduction in appetite.

Administration and effectiveness

For type 2 diabetes, semaglutide may be administered as a once-weekly injection (Ozempic) or can be taken on a daily basis as an oral tablet in a formulation marketed as Rybelsus. For weight loss, the drug is given as a once-weekly injection of Wegovy. To achieve weight loss, semaglutide is administered in higher doses than it is in antidiabetic formulations. Some patients who take semaglutide for type 2 diabetes, however, may experience weight loss as a side effect.

Semaglutide is highly effective in the treatment of type 2 diabetes. Patients often experience significant improvement in blood glucose control as well as reduction in blood pressure and cholesterol levels, resulting in an overall decrease in risk of cardiovascular disease and other potential adverse outcomes associated with type 2 diabetes. Semaglutide also is associated with significant reductions in body weight when used for long-term weight management and when combined with a healthy diet and exercise program. In clinical studies, for example, over the course of more than 15 months of treatment, patients lost on average roughly 15 percent of their body weight. Once treatment is stopped, however, patients typically regain the weight they lost.

Side effects

Semaglutide use is associated with various side effects, many of which affect the gastrointestinal tract and are relatively minor. Examples of such side effects include belching, bloating, constipation, diarrhea, heartburn, and stomach discomfort. Some patients may experience dizziness, headache, or fatigue, and still others may experience more concerning side effects, such as severe nausea, stomach pain, yellowing of the skin or eyes, or vomiting.

Especially severe side effects, including heart attack, high blood pressure, and stroke, are associated with the use of compounded versions of semaglutide. Compounded semaglutide became increasingly widespread in the United States following the drug’s approval for chronic weight management. Increased demand and consequent shortages in supply fueled drug compounding, in which other agents are combined and mixed with semaglutide. In some instances, however, semaglutide base— the active ingredient in approved versions of the drug—was missing from compounded drugs made available to consumers. Rather, the compounded versions contained salt forms of semaglutide, such as semaglutide sodium and semaglutide acetate, the use of which was not approved by the FDA. Moreover, absence of instruction on how to correctly administer compounded formulations raised the risk of improper administration and overdose.