The two phase 3 studies, PRONTO-T1D and PRONTO-T2D, evaluated the safety and efficacy of URLi compared to Humalog in adults with type 1 and type 2 diabetes, respectively. Both studies met the primary endpoint of non-inferior A1C reduction from baseline compared to Humalog at 26 weeks, when the insulins were dosed at mealtime. Further, URLi demonstrated superior reduction in blood glucose spikes at both one hour (-27.9 mg/dL [T1D], -11.8 mg/dL [T2D]) and two hours (-31.2 mg/dL [T1D] and -17.4 mg/dL [T2D]) after a test meal compared to Humalog.
Hypoglycemia is the most common adverse reaction associated with insulin. The studies showed no significant difference in severe, nocturnal or overall hypoglycemia rates reported by study participants.
“Many people taking mealtime insulin are not meeting their A1C goals while also experiencing high blood glucose levels after eating. This may create worry about their ability to achieve good control,” said Dr. Bruce Bode, diabetes specialist at Atlanta Diabetes Associates. “The results from these two studies suggest that URLi may help control blood glucose after meals, as well as help people reach A1C goals.”
The PRONTO studies were designed as treat-to-target, which enables clinicians to determine differences in other important treatment effects – such as rates of hypoglycemia, post-meal glucose control and glucose time in range – at the same level of glycemic control. A sub-set of participants in PRONTO-T1D were evaluated using blinded continuous glucose monitoring to provide more complete information on daily blood glucose patterns. At 26 weeks, URLi demonstrated a significantly better blood glucose profile up to four hours after breakfast compared to Humalog. The study further showed that URLi had significantly longer (+43.6 minutes) time in range (71-180 mg/dL) during the day and similar time in range during the night compared to Humalog.
Data from a phase 1 clinical pharmacology study in people with type 1 diabetes also demonstrated URLi’s effect on post-meal blood glucose control. Results showed URLi was absorbed significantly faster into the blood stream compared to Humalog, insulin aspart and fast-acting insulin aspart. URLi also showed lower blood glucose spikes after a test meal compared to the insulins tested, which was significant compared to Humalog and insulin aspart. Additionally, the early blood glucose profile with URLi closely matched that of participants without diabetes.
“We’re developing URLi to provide a mealtime insulin option that more closely mirrors the way insulin works in people without diabetes,” said Dr. Tom Hardy, senior medical director at Lilly. “If approved, URLi will offer a new mealtime insulin option that, in clinical trials, showed similar A1C reductions to Humalog with significant improvements in post-meal blood glucose after a test meal.”
Lilly submitted applications for URLi with regulatory authorities in Europe and Japan and plans to submit in the U.S. later this year.