Following my article yesterday on how the UT Health Science Center Is At The Forefront Of Testing “Triple Therapy” For New-Onset Diabetics, San Diego-based Elcelyx Therapeutics has released the primary data for Phase 2a clinical trials of NewMet. The study suggested that, contrary to popular belief, the primary site of action of metformin is in the lower gut, indicating that high serum concentration of metformin does not affect blood sugar control. Dr. Ralph DeFronzo, Professor of Medicine and Chief of the Diabetes Division at the University of Texas Health Science Center and the Audie L. Murphy Memorial Veterans Administration Hospital in San Antonio will present the results of the study on Sunday at 2013 American Diabetes Association Scientific Sessions.
Details of Phase 2a clinical trial of NewMet:
As part of the Phase 2a clinical trials, investigators compared the delayed-release formulation of metformin (the NewMet) with the generic metformin to study the blood sugar control in type 2 Diabetics. 24 type 2 diabetics were enrolled in this randomized, three-way cross-over and double-blind study. The patients received twice-daily oral dosing of metformin HCl in a dose of 1,000 mg (immediate release), high dose NewMet (1,000 mg) and low dose NewMet (500 mg) for a period of five days. Each treatment regimen was followed by a wash-out period of 1 week.
The study indicated that the NewMet specifically targets lower gut and decraese the absorption of glucose after meals.
As part of the cross-over study, it was observed that the blood sugar control from NewMet (checked by serial measurement of fasting and post-meal glucose concentration) is equivalent to generic metformin. It was also observed that serum concentration of metformin was 45% lower with high- dose NewMet and 57% lower with low- dose NewMet when compared to generic metformin. In addition, patients on NewMet also reported far less side effects than those who were on generic metformin.
How does NewMet compare to generic metformin for blood sugar control in Type 2 Diabetics?
The study clearly revealed that, besides lower gastrointestinal symptoms, there are a number of other factors that makes NewMet a superior option over generic metformin in special groups like patients with moderate renal impairment. These patients are unable to use generic metformin due to a higher risk of developing lactic acidosis; however, since NewMet exert optimal function with 45% less serum concentration, it can be used by patients with compromised renal function.
The advisor of the phase 2a clinical study, John Buse from of North Carolina School of Medicine, Chapel Hill commented:
“Metformin is the preferred initial pharmacological agent for Type 2 diabetes, but in the U.S., 40% of patients with diabetes are not taking it primarily due to issues of GI tolerability or due to the contraindication of their renal impairment. Moreover, of the 60% who are taking metformin, only about 40% are able to titrate to fully effective doses due to tolerability issues. The NewMet results to date hold the promise of addressing all these patient segments. This is very encouraging news for physicians who would like to be in compliance with ADA treatment guidelines and have their patients benefit from metformin therapy.”
Phase 2b of the NewMet study is already underway to study and confirm the results that have been obtained so far. The double-blind, multi-center study is investigating the safe or optimal dose in patients by testing out once daily formulations of 600, 800 or 1000 milligrams. In addition, the study is also associated with two comparator arms that are using 1,000 and 2,000 milligrams, once daily dose of generic metformin. To read more about the phase 2b clinical trial, take a look at my previous article from May 21st, 2013, “Elcelyx Therapeutics Enrolling Phase 2b Trial For Its Type 2 Diabetes Drug NewMet.”
Objectives for future study and investigation:
A so-called “late breaker” poster or model will be released by the senior Vice President of Research & Development at Elcelyx, Mark Fineman that will help to predict the probable metformin concentration in serum with NewMet when drug is consumed in optimal concentration by renal compromised patients (with mild, moderate or severe renal impairment). The model indicates that the metformin concentration in serum (ad thereby the risk of lactic acidosis) will not increase with NewMet administration in kidney patients.
A new pharmacokinetic study will be initiated in this summer by Elcelyx Therapeutics to confirm the efficacy and predictive value of model in Type 2 diabetics who have some degree of renal impairment (mild, moderate or severe renal disease).