Elcelyx Therapeutics has reported that its Phase 2b dose-ranging study met the primary endpoint of indicating a statistically significant reduction in HbA1c at 16 weeks with Metformin Delayed Release (Metformin DR) compared with placebo in subjects with type 2 diabetes.
The Metformin DR has been designed to target metformin delivery to the lower small intestine, where the product is minimally absorbed but elicits glucose lowering effects.
VA San Diego Healthcare System endocrinology and metabolism chief and University of California San Diego School of Medicine professor of medicine Robert Henry said: “Patients with type 2 diabetes whose advanced kidney disease prevents them from effectively clearing metformin from their circulation are at increased risk for potentially toxic metformin-associated lactic acidosis.
“Gut-mediated Metformin DR has minimal absorption leading to lower systemic exposure with clinically relevant glucose lowering effects and is an especially attractive proposition for the treatment of type 2 diabetes patients with renal impairment, as well as for patients unable to take full doses of metformin due to gastrointestinal side effects.”
The multicentre, randomised, Phase IIb study examined 571 type 2 diabetic patients to assess the glycemic effects of Metformin DR at doses of 600mg, 900mg, 1,200mg and 1,500mg administered on a once-daily basis.
The study also had a single-blind comparator arm of patients treated with 2,000mg of metformin immediate release (IR) each day.
Results suggested that Metformin DR triggered dose-related reductions compared with placebo in HbA1c and fasting plasma glucose.
The glycemic effect of Metformin DR was somewhat less than that seen with a maximally effective dose of metformin immediate release (IR), but with a significantly and disproportionally lower systemic exposure.
The subgroup of subjects who finished the study and followed all protocol requirements showed a pattern of glycemic improvement comparable to that seen with the overall study population.
Metformin DR was well tolerated and adverse events were consistent with the well-understood safety profile of metformin, with the most common ones being gastrointestinal effects such as diarrhea and nausea.
Metformin DR indicated a favourable gastrointestinal side effect profile that requires further development.