Metformin Delayed-Release (DR)
The investigational new drug, a delayed-release metformin, is a low‑dose tablet formulation of the foundational treatment for type 2 diabetes. By reducing systemic exposure, Metformin DR may allow for metformin use in type 2 patients with moderate to severe renal impairment and may decrease metformin’s gastro-intestinal side effects.
Elcelyx has not changed the way metformin works but instead, has discovered how metformin works and leverages this understanding to develop an innovative product that may meet the needs of patients who currently cannot use metformin. Rather than acting through the circulation, Elcelyx has demonstrated that metformin acts at the lower bowel to activate signals leading to glucose regulation.
Metformin DR is delivered to the distal small intestine, maintaining metformin’s effect on glucose, but significantly reducing systemic exposure. This reduction in systemic exposure may allow for metformin use in type 2 patients with moderate to severe renal impairment, a population that is presently contraindicated for metformin use. Also, because metformin is not wasted to circulation, lower doses can be used and with bypassing the upper GI, improvements in tolerance can be realized without titration.
A potentially improved safety and tolerability profile could make Metformin DR appropriate for patients who are currently contraindicated for metformin and those who would benefit from the glucose control provided by metformin but who cannot tolerate currently available formulations, both significant sub-populations of type 2 diabetes patients. Because Metformin DR can deliver an effective dose of metformin, it is an ideal candidate for fixed-dose combinations with other oral antidiabetic agents. Metformin DR offers the potential to be the only metformin/DPP4i FDC with an effective metformin dose in a once-daily formulation that may not require titration.
In a completed 12-week Phase 2b clinical study in 240 subjects with type 2 diabetes, multiple doses of Metformin DR demonstrated statistically significant reductions in fasting plasma glucose at four weeks as compared to placebo. The 12-week data confirm the durability of the effect observed at 4 weeks.