Before insulin was discovered in 1921, people with type 1 diabetes (T1D) didn’t live very long. Its discovery was a great breakthrough and saved lives, but since then the basic management of T1D has continued to remain focused solely on insulin therapy. That could now be changing based on the goals of the recently formed partnership between JDRF and Lexicon Pharmaceuticals.
People with T1D struggle to manage their glucose levels with insulin. Too much insulin can result in low blood glucose levels or hypoglycemia which can cause confusion, lightheadedness, blurry vision and other potentially serious symptoms. Too little insulin results in high blood glucose readings or hyperglycemia and the increased risks of serious long-term complications including kidney failure, blindness, nerve damage, heart attack and stroke.
To help individuals with T1D improve their glucose control and potentially reduce their use of insulin with no increase in hyperglycemia, JDRF has partnered with Lexicon Pharmaceuticals, Inc, to conduct a Phase 2, randomized, double-masked, placebo-controlled clinical trial to evaluate the efficacy and safety of a novel drug with the code number, LX4211, as a co-therapy with insulin.
LX4211 is a first-in-class, inhibitor of two glucose uptake mechanisms (SGLT1 and SGLT2) in the GI tract and kidneys that is designed to lower blood glucose levels through two insulin-independent mechanisms of action and will be taken as a pill (see graphic). In a previous clinical trial of LX4211 in T1D, LX4211 treatment significantly improved glucose control HbA1c levels by 0.55% compared to only 0.06% with placebo over a four-week treatment period. Additionally, LX4211 reduced the total daily mealtime insulin dose by 32% compared to 6% for placebo, while reducing variability in blood glucose levels.
In the planned new study, approximately 76 adolescents and young adults up to age 30 years with HbA1c levels greater than 9.0% will be randomly assigned to receive either placebo or a once daily 400mg dose of LX4211 over a 12-week treatment period, in addition to their current regimen of insulin. The primary objective of the study is to determine if LX4211 is superior to placebo as adjunct to insulin treatment in reducing HbA1c levels at 12 weeks as well as several secondary endpoints, including reduced variability in blood glucose levels and lower insulin needs. The target population chosen for this study is otherwise struggling to reduce their HbA1c levels below 9.0% and is predicted to most benefit from LX4211 treatment.
This collaboration is part of JDRF’s Glucose Control Research Program whose goal is to develop and deliver improved insulin and non-insulin adjunct therapies that improve glucose and overall metabolic control in individuals with T1D.