title: Efficacy and safety of oral methazolamide in patients with type 2 diabetes: a 24-week, placebo-controlled, double-blind study.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of methazolamide as a potential therapy for type 2 diabetes.
  
  
  METHODS
  This double-blind, placebo-controlled study randomized 76 patients to oral methazolamide (40 mg b.i.d.) or placebo for 24 weeks. The primary efficacy end point for methazolamide treatment was a placebo-corrected reduction in HbA1c from baseline after 24 weeks (ΔHbA1c).
  
  
  RESULTS
  Mean ± SD baseline HbA1c was 7.1 ± 0.7% (54 ± 5 mmol/mol; n = 37) and 7.4 ± 0.6% (57 ± 5 mmol/mol; n = 39) in the methazolamide and placebo groups, respectively. Methazolamide treatment was associated with a ΔHbA1c of -0.39% (95% CI -0.82, 0.04; P < 0.05) (-4.3 mmol/mol [-9.0, 0.4]), an increase in the proportion of patients achieving HbA1c ≤6.5% (48 mmol/mol) from 8 to 33%, a rapid reduction in alanine aminotransferase (∼10 units/L), and weight loss (2%) in metformin-cotreated patients.
  
  
  CONCLUSIONS
  Methazolamide is the archetype for a new intervention in type 2 diabetes with clinical benefits beyond glucose control.
authors.affiliation: Box Hill Hospital, Box Hill, Victoria, Australia.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Simpson
authors.affiliation: Department of Clinical and Biomedical Sciences, Geelong Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Nicholson
authors.affiliation: Heidelberg Repatriation Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Joseph
authors.initials: J
authors.lastname: Proietto
authors.affiliation: Clinical Trial Unit, Department of Medicine, Barwon Health, Geelong, Victoria, Australia.
authors.forename: Alana
authors.initials: A
authors.lastname: Sarah
authors.affiliation: Department of Clinical and Biomedical Sciences, Geelong Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Kerrie M
authors.initials: KM
authors.lastname: Sanders
authors.affiliation: Box Hill Hospital, Box Hill, Victoria, Australia.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Phillips
authors.affiliation: Clinical Trial Unit, Department of Medicine, Barwon Health, Geelong, Victoria, Australia.
authors.forename: Jo
authors.initials: J
authors.lastname: Chambers
authors.affiliation: Deakin University, Geelong, Victoria, Australia.
authors.forename: Rob
authors.initials: R
authors.lastname: MacGinley
authors.affiliation: Department of Epidemiology and Preventive Medicine, Barwon Health/Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia.
authors.forename: Neil
authors.initials: N
authors.lastname: Orford
authors.affiliation: Deakin University, Geelong, Victoria, Australia.
authors.forename: Ken
authors.initials: K
authors.lastname: Walder
authors.affiliation: Verva Pharmaceuticals, Ltd., Southbank, Victoria, Australia.
authors.forename: Guy
authors.initials: G
authors.lastname: Krippner
authors.affiliation: Verva Pharmaceuticals, Ltd., Southbank, Victoria, Australia.
authors.forename: Kathy
authors.initials: K
authors.lastname: Skoff
authors.affiliation: Verva Pharmaceuticals, Ltd., Southbank, Victoria, Australia. vwacher@vervapharma.com.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Wacher
mesh_terms: D000368:Aged; D002257:Carbonic Anhydrase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008704:Methazolamide / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015431:Weight Loss / Q000187:drug effects
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D008704:Methazolamide