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Glaucoma Drug Possible New Treatment for Diabetes

Sep 12, 2014
 

Methazolamide, proven in a study to be beneficial in diabetes treatment, could be the archetype for a new class of agents used to treat type 2 diabetes and related conditions…. 

Methazolamide is a carbonic-anhydrase (CA) inhibitor used to treat increased pressure inside the eye due to glaucoma, and it was FDA-approved in 1959.

A 24-week, double-blind, randomized, placebo-controlled study was conducted by Richard W. Simpson, DM, FRCP, a researcher at Box Hill Hospital in Victoria, Australia. This proof-of-concept study consisted of 76 patients with type 2 diabetes, 41 of whom were also taking metformin. The results indicated that methazolamide decreased HbA1c levels by 0.39% (p <0.05). In addition to its HbA1c-lowering effects, researchers found that it caused a known side effect of metabolic acidosis in 7 out of 37 patients, amounting to a rate of 19%, which did not lead to clinically significant symptoms or study withdrawals. It also caused a 10 units/L drop in alanine aminotransferase in 22 patients who were concomitantly taking metformin. The patients taking metformin and methazolamide also experienced an average weight loss of 2.2 kg compared with the placebo group, who had only an average weight loss of 0.3 kg.

Vincent J. Wacher, PhD, said that rather than pursuing methazolamide in its current form as the new method of type 2 diabetes treatment, the researchers of this study are hoping to modify this drug to create an archetype for a new class of antidiabetic agents partly because they don’t believe its glucose-lowering effects are due to the drug’s CA-inhibiting mechanism. In a statement, he added that, "Our preclinical and mechanistic work has shown that methazolamide exerts its metabolic effect by a mitochondrial mode of action that is distinct from its antiglaucoma activity (CA inhibition) and hasn’t previously been evaluated in diabetes." Dr. Wacher further explained that since methazolamide is off patent, they hope to develop a next-generation analog molecule with an optimized glucose-lowering mechanism of action that could also be engineered to take away the CA-inhibiting effect of this drug which causes the metabolic acidosis.

Practice Pearls:
  • Methazolamide proved to be beneficial at lowering glucose and could potentially be useful for other diabetes-related indications
  • Methazolamide may become a next-generation analog molecule with an optimized glucose-lowering mechanism of action
  • Methazolamide decreased HbA1c levels by 0.39%

Published online on Aug 14, 2014 in Diabetes Care