Eli Lilly announced on Mar. 19 that its experimental "triple-G" drug, retatrutide, significantly lowered blood glucose levels in a Phase 3 study involving patients with type 2 diabetes.
The results are important as they suggest retatrutide could offer a new treatment option for people with type 2 diabetes who are seeking both improved blood sugar control and weight loss. The findings also indicate the drug may have advantages over existing therapies.
According to analysts at BMO Capital Markets, "These data firmly secured retatrutide as a differentiated option for [type 2 diabetes] patients looking to achieve maximal weight loss." Retatrutide is designed to activate three hormone receptors—GLP-1, GIP, and glucagon—potentially enhancing its effects compared to Lilly's current drugs tirzepatide (marketed as Mounjaro and Zepbound), which target only two of these pathways.
In the TRANSCEND-T2D-1 trial, retatrutide outperformed placebo in reducing A1C levels, an indicator of average blood sugar. Reductions ranged from 1.7% to 2.0% across different doses after 40 weeks of treatment, while those on placebo saw a drop of just 0.8%. The drug also led to weight loss of up to 16.8% at the highest dose tested, compared with a 2.5% reduction in the placebo group. No plateauing effect was observed by the end of the study period.
Retatrutide showed improvements in cholesterol and triglycerides as well. Previous late-stage research (TRIUMPH-4) found that patients lost an average of 26.6% more weight than those on placebo and experienced reduced knee osteoarthritis pain.
However, safety concerns were noted: some patients experienced dysesthesia (an abnormal touch sensation), particularly at higher doses, and gastrointestinal side effects such as nausea and vomiting were reported.
RBC Capital Markets said that while retatrutide's tolerability and A1C reductions were not as strong as Mounjaro's in type 2 diabetes patients, its greater impact on weight loss could make it an attractive choice for those prioritizing this outcome: "While the overall tolerability and A1C reductions were worse compared to Mounjaro in T2D patients, weight-reduction and discontinuation rates favored reta, positioning reta as a viable option for T2D patients where weight loss is a primary goal of therapy," they wrote.
Lilly has not yet announced when it will seek regulatory approval for retatrutide but plans to present more detailed results at an upcoming medical congress.
