Lilly’s Oral GLP-1 Agonist Orforglipron Achieves Weight Loss Comparable to Injected Semaglutide in Phase 2 Trial

Jul 10, 2023 12:28 CST Updated 12:28

Eli Lilly

Global Pharmaceutical R&D and Production Company

June 2022,FDAApprovedNovo NordiskDeveloped by the companySemaglutide（Semaglutide）As a weight-loss drug on the market, the drug quickly gained popularity worldwide in the same year, achieving sales of over 10 billion US dollars. This is a peptide-based GLP-1 receptor.（GLP-1R）Agonist, in previous clinical trials, semaglutide achieved a 15% weight loss effect in obese patients.(Once weekly injection, 2.4mg each time, lasting for 68 weeks), andEli LillyGIPR/GLP-1R Dual Agonist Developed by the CompanyTirzepatide（Tirzepatide）Achieved the strongest weight loss effect of 22.5% to date(Once weekly injection, 15mg each time, for 72 weeks)In addition, Novo Nordisk has also developed an oral version of semaglutide.

Eli Lilly and Company（Eli Lilly）The researchers in "The New England Journal of Medicine》（NEJM）Published a paper titled:Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity Clinical research papers.

In this Phase 2 clinical trial, an oral weight-loss drug developed by Eli LillyOrforglipron, after 36 weeks of treatment at the highest dose,Helped obese individuals lose an average of 14.7% of their weight, an effect comparable to the GLP-1 receptor agonist developed by Novo NordiskSemaglutideThe injectable version showed comparable treatment effects over 68 weeks.

Similar to semaglutide, Orforglipron is also a GLP-1 receptor agonist, but the difference is that the former is a peptide drug, while the latter is a small molecule drug, making it more suitable for oral administration.

This clinical trial involved 272 obese/overweight patients with an average initial weight of 108.7 kilograms. They were either obese patients with a BMI ≥ 30, or patients with a BMI ≥ 27.(But overweight patients who have already developed weight-related health issues,DiabetesExcluding). These participants tested four different medication dosages.（12mg、24mg、36mg、45mg）, and compared with a placebo control. Meanwhile, participants also received counseling on diet and exercise.

Clinical Trial Design

After 36 consecutive weeks of daily oral administration, the average weight loss among participants in each group ranged from 9.4% to 14.7%, while the placebo group experienced only a 2.3% reduction in weight. Specifically, the 12mg dose group lost 9.8kg.（9.4%）, 24mg dose group lost 13.6kg（12.5%）, 36mg dose group lost 14.2kg（13.5%）, 45mg dose group lost 15.4kg（14.7%）The percentages of people who lost more than 10% of their body weight in these four different dosage groups were 46%, 62%, 75%, and 69%, respectively, while only 9% of those in the placebo group lost more than 10% of their body weight.

Weight Loss Effects of Different Dose Groups

In addition, participants taking the drug had triglycerides andCholesterolPositive improvements were also observed in horizontal levels and cardiac systolic pressure.

These results suggest that daily oral administration of Orforglipron is associated with weight loss and related health benefits, and,Within a 36-week treatment period, it achieved weight loss effects comparable to the 68-week results of the injectable GLP-1 receptor agonist semaglutide.

The most common side effects include nausea, constipation, vomiting, and diarrhea. Most side effects are mild to moderate and occur as the drug dose increases. About 10%-17% of participants discontinued the medication due to side effects. The safety profile is comparable to that of injectable GLP-1 receptor agonists. The research team noted that the purpose of this clinical trial is to help determine the optimal dosing and methods for increasing doses over time, in preparation for larger-scale late-stage clinical studies.

Orforglipron is just one of many weight-loss drugs under development by Eli Lilly and Company. Currently, Eli Lilly has launched two Phase 3 clinical trials to further study the efficacy and safety of Orforglipron in treating obesity/overweight and Type 2 diabetes.

Developed by Eli Lilly and CompanyGIPR/GLP-1RDual AgonistTirzepatide（Tirzepatide）It has been successful in Phase 3 clinical trials and is expected to be approved as a weight-loss drug by the end of this year at the earliest.If approved for marketingTirzepatide will become the most effective weight-loss drug. According to predictions, it is very likely to become the best-selling weight-loss drug within the next five years, and possibly even the best-selling drug overall.In addition, Eli LillyOfGCGR/GIPR/GLP-1RTriple agonists have also advanced to Phase 3 clinical trials.

In weight loss drugs andAlzheimer's DiseaseThe success in fields such as pharmaceuticals has led to Eli Lilly and Company's market value reaching new highs continuously, with its latest market value now reaching a staggering$435.6 billion, surpassing Johnson & Johnson's $430 billion, officially becoming the world's most valuable pharmaceutical company.