Eli Lilly's tirzepatide demonstrates benefits in data presented
Results from several studies of Eli Lilly's investigational dual GIP and GLP-1 receptor agonist, 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. A sub-analysis of phase 2b 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 were only partially attributed to weight loss, 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 2b 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 2 study showed dose escalations with tirzepatide resulted in fewer gastrointestinal side effects while maintaining the efficacy seen in the phase 2b study. Reduced study discontinuation rates were also observed. To inform optimal dosing for the phase 3 program, researchers evaluated three tirzepatide dose-escalation regimens to determine impact on composite GI side effects and efficacy. Tirzepatide treatment led to significant A1C reductions and weight loss, consistent with the phase 2b study; GI side effects were mild to moderate in intensity and overall lower than in the phase 2b 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 2b 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 3 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 and body weight after treatment with tirzepatide.3 This study also supports the significant A1C and body weight reductions seen in the phase 2b study, suggesting tirzepatide's potential for effectively treating people with type 2 diabetes is consistent across populations. 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 2b study of people with type 2 diabetes, researchers found that treatment with tirzepatide led to improvements in NASH-related markers. A phase 2b study exploring tirzepatide in NASH will initiate later this year.