Results from a phase 2b clinical trial of Eli Lilly and Company's (NYSE: LLY) dual GIP and GLP-1 receptor agonist (GIP/GLP-1 RA, LY3298176) showed strong and clinically meaningful blood sugar reduction and weight loss in people with type 2 diabetes. The six-month data — showing average HbA1c reductions of up to 2.4 percentage points and an average weight reduction up to 11.3 kg (12.7 percent) – were presented today at the 54th Annual Meeting of the European Association for the Study of Diabetes in Berlin and simultaneously published in The Lancet.1
The weekly dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist integrates the action of both incretins into a single novel molecule, aiming to build upon the clinical benefits seen with a selective GLP-1 RA.
"These phase 2b clinical trial results for GIP/GLP-1 RA are unprecedented, and the impressive blood glucose and weight reductions seen may lead to a new treatment option for people with type 2 diabetes," said Juan P. Frias, M.D., President and Principal Investigator, National Research Institute. "The next wave of innovation in the study of incretins for treating type 2 diabetes is fascinating. We're taking the already proven benefits of GLP-1 receptor agonists and looking at a new molecule that integrates GIP action to see what additional benefits are possible."
Two statistical approaches were used to evaluate the efficacy of four doses of GIP/GLP-1 RA (1 mg, 5 mg, 10 mg, 15 mg) compared to placebo and dulaglutide 1.5 mg in people with type 2 diabetes. The first was a dose response model evaluating the effect regardless of discontinuation of treatment and use of rescue medication. An additional analysis identified the effect while on treatment and without use of rescue medication.*1
At 26 weeks, the primary analysis showed a robust dose response compared to placebo throughout the entire dose range of GIP/GLP-1 RA included in the study.1
The analysis of participants while on treatment comparing GIP/GLP-1 RA to dulaglutide and placebo showed significant improvements across endpoints.1
HbA1c reduction: All GIP/GLP-1 RA doses and dulaglutide showed significant blood sugar improvement (mean absolute reduction) from baseline [GIP/GLP-1 RA: -1.6 percent (5 mg), -2.0 percent (10 mg), and -2.4 percent (15 mg); dulaglutide -1.1 percent (1.5 mg)] compared to placebo (0.1 percent).
HbA1c target: The higher doses of GIP/GLP-1 RA provided the most significant HbA1c reductions, with up to 30 percent of people who received the 10 mg and 15 mg doses achieving HbA1c levels of less than 5.7 percent, which is in the normal range for people without diabetes [18 percent (10 mg) and 30 percent (15 mg)]. Further, up to 90 percent of people reached the recommended HbA1c target of 7 percent or less [GIP/GLP-1 RA: 69.1 percent (5 mg), 90.0 percent (10 mg), and 77.4 percent (15 mg); dulaglutide 51.9 percent (1.5 mg)].
Weight loss: Participants taking GIP/GLP-1 RA achieved significant weight loss [-4.8 kg (5 mg), -8.7 kg (10 mg) and -11.3 kg (15 mg)], as did those taking dulaglutide [-2.7 kg (1.5mg)], compared to placebo (-0.4 kg). More than a third of people lost 10 percent or more of their starting body weight with GIP/GLP-1 RA 10 mg (39.2 percent) and 15 mg (37.7 percent), and a quarter of people lost 15 percent or more with the 15 mg dose.
The safety profile of GIP/GLP-1 RA was similar to the GLP-1 RA class. The most commonly reported side effects were gastrointestinal-related, and dose-dependent. These events included nausea [20 percent (5 mg), 22 percent (10 mg), 40 percent (15 mg)], diarrhea [24 percent (5 and 10 mg), 32 percent (15 mg)] and vomiting [8 percent (5 mg), 16 percent (10 mg), 26 percent (15 mg)], which were mild to moderate and generally temporary, most often occurring during the titration period. Dulaglutide 1.5 mg had a similar side effect profile to previous studies. No participants in any of the treatment groups experienced severe hypoglycemia.1 A further study examining an optimal titration schedule to help manage GI side effects was conducted and will be presented next year.
"Despite the progress we've made in diabetes management, people living with type 2 diabetes often need additional treatments as their condition progresses. That's why our researchers continue innovating — to help make lives better," said Jeff Emmick, M.D., Ph.D., vice president of product development, Lilly Diabetes. "We set a high bar for this phase 2 study, and the results exceeded our expectations. We're excited to continue studying GIP/GLP-1 RA and hope to add it to our wide range of therapies for people with diabetes."
The safety and efficacy of Lilly's GIP/GLP-1 RA are being studied further in a large phase 3 clinical program that will be referred to as the SURPASS program. Phase 3 studies for type 2 diabetes are expected to begin no later than early 2019 and complete in late 2021. Lilly is evaluating next steps in the study of GIP/GLP-1 RA for obesity and other conditions.