Eli Lilly Highlights Tirzepatide’s Potential Across Multiple Metabolic Diseases at ADA 2019

June 11, 2019 /BioValleyBIOON/ -- US pharmaceutical giantEli Lilly(Eli Lilly) recently in the United StatesDiabetesAmerican Diabetes Association (ADA) 79th ScientificMeetingResults of multiple clinical studies on the experimental dual GIP and GLP-1 receptor agonist (RA) tirzepatide were published, enhancing the drug’s ability to reduce type 2Diabetesthe potential of patients' blood glucose (A1C) and body weight. Early research results also support the potential benefits of tirzepatide in treating other metabolic diseases.

The following are the research results presented at the ADA meeting: (1) Improvements in β-cell function markers (how pancreatic cells produce, store, and release insulin) and insulin sensitivity (how the body's cells respond to insulin) help explain the efficacy; (2) Efficacy and tolerability were improved with a lower initial dose and smaller subsequent dose increments; (3) After only 8 weeks of treatment, type 2DiabetesPatients exhibited significant reductions in A1C and body weight; (4) in type 2DiabetesAmong the patients, markers of non-alcoholic steatohepatitis (NASH), characterized by liver inflammation and hepatocellular injury due to hepatic steatosis, showed improvement.

Juan P. Frias, Medical Director and Principal Investigator at the National Institutes of Health, stated: “These new tirzepatide data build upon the positive outcomes observed to date in patients with type 2 diabetes. These results provide additional evidence that tirzepatide has the potential to achieve clinically meaningful reductions in blood glucose and body weight in patients with type 2 diabetes, as well as treat otherMetabolic Diseases。”

Subanalysis of the Phase IIb study results demonstrated that tirzepatide improved β-cell function and markers of insulin sensitivity in patients with type 2 diabetes. The improvement in insulin sensitivity markers observed with GLP-1 receptor agonists (GLP-1 RAs) is primarily attributed to weight loss; therefore, researchers further analyzed these markers to better understand whether the GIP component of tirzepatide contributes to a distinct profile. Unlike GLP-1 RAs, the improvements seen with tirzepatide (10 mg and 15 mg) were only partially attributable to weight loss (28% and 22%, respectively), suggesting that the independent effect of GIP on insulin sensitivity may contribute to the robust and clinically meaningful glycemic control observed in the 26-week Phase IIb study.

Data from a 12-week Phase II study demonstrated that dose escalation of tirzepatide reduced gastrointestinal (GI) adverse effects while maintaining the efficacy observed in the Phase IIb study. A reduction in treatment discontinuation rates was also observed. To determine the optimal dosing regimen for the Phase III program, researchers evaluated three tirzepatide dose-escalation schemes to assess their impact on composite GI adverse events (nausea, vomiting, and diarrhea) and efficacy. The results showed:

Consistent with the Phase IIb study, tirzepatide treatment resulted in significant reductions in A1C (up to 2.0%) and body weight (up to 5.7 kg).

Gastrointestinal side effects were mild to moderate in severity and overall lower than those observed in the Phase IIb study. The treatment discontinuation rate due to adverse events with tirzepatide was less than 5%, comparable to that of placebo, and overall lower than in the Phase IIb study.

Data from this study and other tirzepatide studies, along with modeling, demonstrated that a lower initial dose and smaller incremental dose titration improve tolerability, which informed the selected dosing regimen for the Phase III clinical program (SURPASS) initiated in the second half of 2018.

Another 8-week clinical study in Japanese patients with type 2 diabetes showed that tirzepatide significantly reduced A1C (by up to 2.05%) and body weight (by up to 5.1 kg). This study also supports the significant reductions in A1C and body weight observed in the Phase IIb studies, suggesting that the potential of tirzepatide for effectively treating patients with type 2 diabetes is consistent across different populations.

Given the relationship between NASH and type 2 diabetes, researchers analyzed the effects of tirzepatide on several NASH-related biomarkers. In an analysis of a Phase IIb study in patients with type 2 diabetes, researchers found that treatment with tirzepatide improved NASH-related biomarkers. A Phase IIb study exploring the potential of tirzepatide for the treatment of NASH will be initiated later this year.

Eli LillyDr. Brad Woodward, Global Development Lead for Incretins, stated, “We are excited about the potential of tirzepatide to make a significant impact in patients with type 2 diabetes and other conditions, including obesity and NASH. The results from early- and mid-stage trials have paved the way for our extensive Phase III program, reinforcing our commitment to further exploring its use in diverse populations and supporting its potential to address unmet medical needs.” (Bioon.com)

Original Source:Eli Lilly Official Website