Triple oral fixed-dose diabetes polypill versus insulin plus metformin efficacy demonstration study in the treatment of advanced type 2 diabetes (TrIED study-II)

Diabetes Obes Metab. 2011 Sep;13(9):800-5. doi: 10.1111/j.1463-1326.2011.01408.x.

Abstract

Aim: To compare the efficacy of a fixed-dose triple oral diabetes polypill containing 1 or 2 mg glimepiride, 500 mg sustained-release metformin, and 15 mg pioglitazone (GMP) administered once daily with human insulin 70/30 mix and 500 mg sustained-release metformin administered twice daily (IM) in insulin-naÏve subjects with type 2 diabetes mellitus inadequately controlled [haemoglobin A1c (HbA1c) over 8.0%] on a combination of glimepiride and metformin.

Methods: One hundred and one subjects were randomized to GMP or IM regimens for 12 weeks. The primary outcome was the change in HbA1c and secondary outcomes were changes in fasting plasma, and postprandial plasma glucoses and the number of patients achieving a drop in HbA1c of over 1%. Other secondary outcomes were changes in the lipid profile, C-peptide level, body weight as well as physician assessments of efficacy and patient assessment of tolerability.

Results: The primary outcome of a change in HbA1c showed a trend towards a lower HbA1c with GMP therapy (-1.33% vs. -0.83%; p = 0.059). The number of subjects achieving a decrease in HbA1c of greater than 1.0% was significantly greater in the GMP therapy (72.5% vs. 22%; p = 0.0001). Both regimens equally and significantly reduced fasting and postprandial glucose levels (p = 0.05). Weight gain was nonsignificantly greater with IM (2.69 vs. 0.92 kg; p = 0.223). Investigator assessment of efficacy was significantly better with GMP (p = 0.001) as was tolerability as assessed by patients (p = 0.0001).

Conclusion: When compared with suboptimally titrated IM there was a trend towards a lower HbA1c with GMP and significantly more GMP subjects obtained an HbA1c under 7%. Global assessments by investigators and subjects showed both a greater efficacy and tolerability with GMP.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • C-Peptide / drug effects
  • C-Peptide / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Combinations
  • Female
  • Glycated Hemoglobin / drug effects*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Patient Satisfaction
  • Pioglitazone
  • Postprandial Period
  • Prospective Studies
  • Sulfonylurea Compounds / administration & dosage*
  • Thiazolidinediones / administration & dosage*
  • Treatment Outcome

Substances

  • Blood Glucose
  • C-Peptide
  • Drug Combinations
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • glimepiride
  • Metformin
  • Pioglitazone