What is the difference between Ozempic and Wegovy?

Ozempic and Wegovy have been constantly in the news, or is it Wegovy and Ozempic? What is the difference between the two? 

Both are GLP-1 receptor agonists (activators of the GLP-1 receptor), and sometimes are referred to as incretins for their ability to stimulate insulin secretion. GLP-1 is a peptide hormone (30-31 amino acids long) that activates GLP-1 receptor, which is a G-protein coupled receptor (GPCR).  It is released from the intestines in response to food intake, particularly after the ingestion of carbohydrates and fats, and plays a crucial role in regulating blood sugar levels via the following functions:

• Insulin Secretion: GLP-1 promotes the secretion of insulin, a hormone that helps lower blood sugar levels, from the pancreas. It enhances the body's insulin response to food intake, making it a critical player in glucose homeostasis (maintaining blood sugar levels within a normal range).
• Glucagon Suppression: GLP-1 also suppresses the secretion of glucagon, a hormone that increases blood sugar levels, from the pancreas. By suppressing glucagon, GLP-1 helps to lower blood sugar levels, especially postprandially (after meals).
• Gastric Emptying: GLP-1 slows down the rate at which the stomach empties, which can help to reduce the rapid rise in blood sugar that can occur after eating.
• Appetite Regulation: Additionally, GLP-1 has been shown to promote satiety, or feelings of fullness, which can help with weight management.

The last property has been somewhat a surprise based on our previous understanding of GLP-1, and incretins more generally. But this ability to suppress appetite and lead to weight loss has made both drugs a hot commodity.

Ozempic and Wegovy share the same active ingredient: Semaglutide, which is a peptide analog of GLP-1 (Figure 1). Compared to GLP-1, semaglutide has changes to the sequence (e.g. deleting first 6 amino acids), and the use of a modified amino acid. These changes are designed to improve the pharmacodynamic/kinetic properties of the drug. They both are administered via subcutaneous injection.

The primary differences between Ozempic and Wegovy are in (1) dosage and formulation, and more importantly (2) marketing and medical uses. With respect to the first difference, Wegovy is given at a slightly higher dosage than Ozempic. This is primarily because of the second difference which is that Ozempic has been approved for treating type 2 diabetes, whereas Wegovy has been approved for weight management. As a result, the two drugs (which are essentially the same) are marketed to two different patient populations.

Interestingly, semaglutide products were not the first FDA-approved drugs in the incretin category. That distinction goes to exenatide (brand name Byetta) which was approved back in 2005 for lowering blood sugar in type 2 diabetes patients. In the intervening years a number of other GLP-1 agonists emerged tweaking the structure in an attempt to increase efficacy activating GLP-1 receptor (pharmacodynamics), as well as improving stability in the blood enabling weekly dosing instead of daily dosing (pharmacokinetics).

The field continues to move ahead with next-generation drugs starting to appear. In particular, tirzepatide (brand name Mounjaro) represents a new class of drugs called GLP-1/GOP agonists, which not only activate GLP-1 receptor, but also glucose-dependent insulinotropic polypeptide (GIP) receptor. GIP is another incretin secreted by the gut.

In head-to-head trials, recent data indicate that Mounjaro may be slightly more effective at controlling blood sugar (A1C levels) than Ozempic, and lead to greater weight loss (link). Mounjaro is currently authorized solely for treating Type 2 diabetes. However, ongoing research is exploring expanding the label to include weight management.

Another dimension to the GLP-1 story is that GLP-1 agonists such as Ozempic and Wegovy have been shown to reduce the occurrence of adverse cardiovascular events such as stroke, heart failure, and heart attacks in large cardiovascular outcomes trials. Although not surprising on the surface (i.e. diabetes and obesity are cardiovascular risk factors), these findings were more robust than expected, and this topic will be the subject of a future post.

Figure 1. Ozempic and Wegovy possess the same active ingredient (semaglutide) that is injected subcutaneously targeting two different patient populations: type 2 diabetes (Ozempic) and weight loss (Wegovy).