MicroBiome TherapeuticsTM LLC, (MBT) has reported positive topline results from a proof of concept study testing whether its investigational drug, NM 505, can improve the tolerability of metformin, the first-line therapy for Type 2 diabetes worldwide. NM505 is a combination of metformin and active ingredients contained in the company's lead microbiome modulator, NM504.
Metformin, an effective, safe and inexpensive medication, is recommended for initial treatment of Type 2 diabetes by the American Diabetes Association and others. However, diarrhea is a well-known side effect of metformin therapy, affecting an estimated 20% of patients. Physicians report diarrhea as a frequent cause of metformin discontinuation and dosage limitation.
In this double-blind, randomized, crossover study, a preliminary formulation of NM505 was administered orally to patients with Type 2 diabetes who were metformin intolerant due to gastrointestinal (GI) side effects. Results of the study showed that metformin tolerability was significantly greater with NM505 than with metformin and placebo, as measured by full days on the drug and ability to escalate the dose via more frequent dosing. Higher and more frequent doses of metformin are associated with better blood glucose control. Subjects receiving NM505 showed improvements in fasting blood glucose levels and also reported less severe GI side effects than those receiving metformin and placebo.
Steve Orndorff, PhD, CEO of MicroBiome Therapeutics, noted, "Based on these encouraging results as well as previous data showing that NM504 can improve blood glucose control in diabetes, we are preparing an IND filing for a larger clinical trial that, if successful, would enable us to seek U.S. FDA marketing approval for NM505 via the expedited 505(b)(2) regulatory pathway. Increasing the utility of metformin could decrease reliance on oral second-line anti-diabetes therapies, which are expensive and carry risks of potentially serious side effects."
In an earlier clinical study in prediabetic and Type 2 diabetes patients, microbiome modulator NM504 shifted the gut microflora in beneficial ways, significantly improving post prandial blood glucose and insulin levels. This suggests that the modulators in NM504 may offer an additional glucose-lowering mechanism, which when combined with metformin could potentially deliver superior glycemic control as well as reduced side effects compared to currently-approved metformin formulations.
The concept for NM505 stems from 2012, when a newly diagnosed Type 2 diabetic who was unable to tolerate metformin received NM504 as adjunctive therapy. A published case report described how co-administration of NM504 eliminated the dose-limiting diarrhea in this patient and resulted in greater reduction in fasting blood glucose levels than would have been expected with metformin alone.