GLP-1 Medications Compared

Rybelsus is the only oral GLP-1 receptor agonist on the market. It contains the same active ingredient as Ozempic and Wegovy (semaglutide) but is formulated as a tablet for patients who prefer not to inject. It is FDA-approved for improving blood sugar control in adults with type 2 diabetes, but is not approved for weight loss.

Because peptides are normally broken down in the stomach, Rybelsus uses a novel co-formulation with SNAC, a small molecule that transiently raises stomach pH and protects semaglutide long enough for it to absorb through the gastric mucosa. This makes Rybelsus extremely sensitive to how it is taken — it must be swallowed whole with a small amount of plain water on an empty stomach, and the patient must wait before eating, drinking anything other than water, or taking other medications.

Ozempic is a once-weekly injectable semaglutide approved for type 2 diabetes and to reduce the risk of major cardiovascular events (heart attack, stroke) in adults with type 2 diabetes and established cardiovascular disease. It is among the most studied GLP-1 medications, with robust clinical trial data including the SUSTAIN and SUSTAIN-6 programs. While Ozempic is widely prescribed off-label for weight loss, Wegovy is the FDA-approved weight-loss formulation of semaglutide.

Wegovy is the higher-strength formulation of semaglutide approved specifically for chronic weight management in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related condition such as high blood pressure, type 2 diabetes, or high cholesterol. In the STEP clinical trial program, Wegovy produced average weight loss of approximately 15% of body weight over 68 weeks, which was substantially more than any prior weight-loss medication. It also received FDA approval in 2024 for reducing the risk of serious cardiovascular events in adults with cardiovascular disease and obesity or overweight.

Mounjaro (tirzepatide) is a dual GIP/GLP-1 receptor agonist — the first of its class. By activating both receptors, tirzepatide produces effects that appear to exceed those of GLP-1 agonists alone. In the SURPASS clinical trial program, Mounjaro consistently outperformed semaglutide (Ozempic) in head-to-head blood sugar reduction. It is FDA-approved for type 2 diabetes. Its weight-loss counterpart, Zepbound, uses the same molecule but is FDA-approved for obesity.

Zepbound is the weight-management formulation of tirzepatide, FDA-approved in November 2023 for chronic weight management in adults with obesity or overweight with a weight-related condition. In the SURMOUNT trial program, Zepbound produced average weight loss of approximately 20–22% of body weight at the highest strength — the largest weight loss ever seen in a clinical trial for a weight-loss medication. It is also being studied for obstructive sleep apnea and other obesity-related conditions.

Trulicity (dulaglutide) is a once-weekly GLP-1 receptor agonist approved for type 2 diabetes and for reducing cardiovascular risk in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. It uses a unique single-use autoinjector that does not require needle attachment, which some patients find easier to use than pen-style injectors. Dulaglutide is a modified version of human GLP-1 with a half-life long enough for once-weekly dosing.

Bydureon BCise is the extended-release, once-weekly formulation of exenatide. It uses microsphere technology to slowly release exenatide over seven days. It was one of the first once-weekly GLP-1 options available and remains an option for patients who tolerate exenatide well and prefer weekly over twice-daily injections (the older Byetta formulation). It is approved only for type 2 diabetes with no cardiovascular outcomes approval.

Victoza (liraglutide) is a once-daily injectable GLP-1 approved for type 2 diabetes and for reducing the risk of major cardiovascular events in adults with type 2 diabetes and established cardiovascular disease. It was one of the first GLP-1 medications to receive a cardiovascular risk reduction approval (LEADER trial). Liraglutide is also the active ingredient in Saxenda, which is approved for weight management. It requires daily injection, which may be a disadvantage compared to weekly options for some patients.

Saxenda is the weight-management formulation of liraglutide, approved for chronic weight management in adults with obesity or overweight with at least one weight-related condition, and also in adolescents aged 12 and older with obesity. In clinical trials, Saxenda produced average weight loss of 5–8% of body weight. While effective, it has largely been superseded for new patients by weekly options like Wegovy and Zepbound, which tend to produce greater weight loss. It remains an option for patients who have previously responded well to it or for whom weekly injections are not suitable.

Byetta was the first GLP-1 receptor agonist approved in the United States (2005) and pioneered the class. It contains exenatide, a synthetic version of exendin-4, a peptide found in the venom of the Gila monster lizard — which happens to activate the GLP-1 receptor. Byetta requires two injections per day (within 60 minutes before the two main meals), which is the most burdensome injection schedule of any current GLP-1. It has largely been replaced by once-weekly options for new patients but remains available.