What Makes Zepbound and Wegovy Stand Out in the Battle Against Weight Loss?

In the U.S., obesity is a serious public health problem and is closely linked to coronary heart disease, diabetes, high blood pressure, stroke, breathing problems, and sleep problems. More than 70% of American adults are obese or overweight, overwhelmingly the latter, with an associated weight condition. Obese or overweight adults can reduce cardiovascular disease risk through diet and exercise that reduces body weight by 5%–10%.

Traditionally, almost all obesity treatments featured lifestyle-based treatment. Although the physiological counter-regulatory mechanisms stimulated by diet and exercise limit weight loss and have limited utility for the management of obesity led to the realization that this condition is a complex, multi-component metabolic disease. A molecule consisting of both gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP) receptor agonism theoretically may have greater efficacy for weight reduction than either a GIP receptor agonist or a GLP receptor agonist, alone, reveals a recent study. 

In a head-to-head clinical trial, Eli Lily said its weight loss treatment, Zepbound, helped patients lose 47% more relative weight than Novo Nordisk’s obesity treatment, Wegovy, citing Ryan’s statement. Lilly, based in Indianapolis, said its Zepbound came in head and shoulders over the drug Wegovy, which was launched a year earlier, with 20.2% compared with 13.7% weight loss. From December 2019 to April 2022, the study was conducted as a clinical trial by 2539 participants. Participants in the clinical trial lost 50.3 pounds overall, versus 33.1 on Wegovy, an approved drug in the U.S. in March 2022. The figures are from summary (or “topline”) results in a Phase 3 stage-looking clinical trial called Surmount-5, Lilly said.

Zepbound (also known as Tirzepatide, a novel dual GIP/GLP-1 receptor agonist) is a chemically named drug whose action is different for diabetes its chemical name is Tirzepatide, formulated as a synthetic peptide containing 39 amino acids of native GIP sequence. Tirzepatide appears to have potent glucose lowering and weight loss, with adverse effects similar to those of established GLP 1 receptor agonists in pre-clinical trials and phase 1 and 2 clinical trials.

U.S. Food and Drug Administration approved Zepbound (tirzepatide) injection for chronic weight management in adults with obesity (body mass index of 30 kilograms per square meter (kg/m²) or greater) or overweight (body mass index of 27 kg/m² or greater) and at least one weight-related condition, including high blood pressure, type 2 diabetes or high cholesterol for use. 

Zepbound also shouldn’t be used in patients with a history of severe allergic reactions to tirzepatide (its active ingredient), or any of the other ingredients in Zepbound, according to FDA. If it is suspected a severe allergic reaction, patients should stop taking Zepbound and see a doctor immediately. Warnings in the Zepbound include inflammation of the pancreas (pancreatitis), gallbladder trouble, acute kidney injury, diabetic retinopathy (damage to the eye’s retina) in patients with type 2 diabetes mellitus, and suicidal behavior or thinking.

Another popular weight treatment Wegovy is also made by Novo Nordisk, based in Copenhagen, Denmark, as well as the diabetes treatment Ozempic. They both use the same active pharmaceutical ingredient, called semaglutide. This drug differs from human GLP-1 in two amino acid substitutions at positions Aib(8) and Arg(34) and at position 26 is derivatized as lysine.

In the trial of adults with obesity or being overweight with one or more of the characteristics of a weight-related medical condition but without diabetes, the study showed that at 72 weeks, Zepbound beat Wegovy at both the coprimary and secondary endpoints.

In addition, in a key secondary endpoint, 31.6% of people taking Zepbound lost at least 25% of their body weight, compared to 16.1% of people taking Wegovy, Lilly noted. In the SURMOUNT clinical trial, the most frequently reported adverse events were gastrointestinal and were generally mild to moderate in severity for both Zepbound and Wegovy.

In conclusion, the drug that is to be more beneficial for you depends on your detailed health condition as well as the desired weight loss. Finally, always consult your physician before starting any medication because your medical record and medical history are equally important in knowing how your body is going to react to any specific drug. 

To learn more about Wegovy’s active ingredient, Semaglutide, visit our Semaglutide page.

Reference: Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038

John Russell. Trial shows Lilly’s Zepbound helps patients lose far more weight than competing drug – Indianapolis Business Journal. Indianapolis Business Journal. Published December 4, 2024. https://www.ibj.com/articles/lilly-says-its-zepbound-weight-loss-treatment-helped-patients-lose-47-more-weight-than-novo-nodisks-wegovy