Results from studies of dual GIP and GLP-1 receptor agonist tirzepatide reinforce its potential in lowering A1C and body weight in type 2 diabetes

Results from several studies of Eli Lilly and Company's investigational dual GIP and GLP-1 receptor agonist (RA), tirzepatide, reinforce its potential in lowering A1C and body weight in people with type 2 diabetes. Early research results also support tirzepatide's potential benefit in treating other metabolic conditions.

The following findings were presented in oral and poster presentations at the American Diabetes Association's 79th Scientific Sessions in San Francisco: - Improvements in markers of beta cell function (how cells in the pancreas produce, store and release insulin) and insulin sensitivity (how cells in the body respond to insulin) that help explain efficacy;- efficacy and improved tolerability with lower initial doses and smaller subsequent dose escalations; significant A1C and body weight reductions in Japanese people with type 2 diabetes after just eight weeks of treatment; and improvements in markers of non-alcoholic steatohepatitis (NASH, liver inflammation and cell damage caused by liver fat) in people with type 2 diabetes.

Tirzepatide shows improvements in markers that help explain efficacy : A sub-analysis of phase IIb results show tirzepatide improved markers of beta cell function and insulin sensitivity in people with type 2 diabetes. Improvements in insulin sensitivity markers seen with GLP-1 RAs have been primarily explained by weight loss; therefore, researchers further analyzed these markers to better understand if the GIP action in tirzepatide contributes to a unique profile. Unlike GLP-1 RAs, the improvements seen with tirzepatide (10 mg and 15 mg) were only partially attributed to weight loss (28 percent and 22 percent, respectively), suggesting an independent effect of GIP on insulin sensitivity may contribute to the strong and clinically meaningful blood glucose control seen in the 26-week phase IIb study.

Tirzepatide shows consistent positive impact on blood glucose control and weight loss while improving tolerability with dose escalations: Data from a 12-week, phase II study showed dose escalations with tirzepatide resulted in fewer gastrointestinal (GI) side effects while maintaining the efficacy seen in the phase IIb study. Reduced study discontinuation rates were also observed. To inform optimal dosing for the phase III program, researchers evaluated three tirzepatide dose-escalation regimens to determine impact on composite GI side effects (nausea, vomiting and diarrhea) and efficacy. Results showed: tirzepatide treatment led to significant A1C reductions (up to 2.0 percent) and weight loss (up to 5.7 kg), consistent with the phase IIb study; GI side effects were mild to moderate in intensity and overall lower than in the phase IIb study; treatment discontinuation rates due to adverse events with tirzepatide were less than 5 percent, comparable to placebo and overall lower than in the phase IIb study. Data learned from this and other tirzepatide studies, along with modeling, support that a lower initial dose and smaller incremental dose escalations improve tolerability, which informed the selected dosing approach for the phase III clinical trial program – SURPASS – initiated in late 2018. Results from another study – an eight-week trial in Japanese people with type 2 diabetes – showed significant reductions in A1C (up to 2.05 percent) and body weight (up to 5.1 kg) after treatment with tirzepatide. This study also supports the significant A1C and body weight reductions seen in the phase IIb study, suggesting tirzepatide's potential for effectively treating people with type 2 diabetes is consistent across populations.

Tirzepatide shows potential for therapeutic impact in NASH : Given the relationship between NASH and type 2 diabetes, researchers analyzed tirzepatide's impact on several markers associated with NASH. In an analysis of the phase IIb study of people with type 2 diabetes, researchers found that treatment with tirzepatide led to improvements in NASH-related markers. A phase IIb study exploring tirzepatide in NASH will initiate later this year.

Comment: The safety and efficacy of Lilly's GIP/GLP-1 RA are being studied further in a large phase III clinical program that will be referred to as the SURPASS program . Phase III studies for type 2 diabetes are expected to complete in late 2021. Lilly is evaluating next steps in the study of GIP/GLP-1 RA for obesity and other conditions.

Comment: LY 3298176 results reinforce Lilly's position in the rapidly-growing GLP-1 market versus Novo Nordisk's semaglutide franchise.