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Effect of pioglitazone in combination with insulin therapy on glycaemic control, insulin dose requirement and lipid profile in patients with type 2 diabetes previously poorly controlled with combination therapy
Author(s) -
Berhanu P.,
Perez A.,
Yu S.
Publication year - 2007
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2006.00633.x
Subject(s) - pioglitazone , metformin , medicine , placebo , insulin , type 2 diabetes , endocrinology , dose , combination therapy , diabetes mellitus , triglyceride , gastroenterology , cholesterol , alternative medicine , pathology
Aim: The aim of this randomized placebo‐controlled study was to evaluate the safety and efficacy of pioglitazone administered alone or in combination with metformin in reducing insulin dosage requirements for improved glycaemic control in patients with type 2 diabetes previously poorly controlled with combination therapy. Methods: In this multicentre, double‐blind study, 222 patients with haemoglobin A1c (HbA 1c )>8.0% at screening treated with combination therapy initially were given titrated insulin therapy (to fasting plasma glucose <140 mg/dl) and then were randomly assigned to 20‐week treatment with pioglitazone or placebo in combination with insulin, with or without concurrent metformin therapy. More than 98% of patients were taking metformin prior to and during the study. Results: Pioglitazone significantly reduced (p < 0.05) insulin dose requirements 2 weeks after treatment initiation. At study end relative to baseline, pioglitazone reduced daily insulin dosages by 12.0 units (p < 0.001), a 21.5% (12.0/55.8 units at baseline) group mean average reduction. Relative to placebo, pioglitazone reduced daily insulin dosages by 12.7 units [95% confidence interval [CI]: −17.5, −8.0], while improving mean HbA 1c levels [adjusted mean HbA 1c change: pioglitazone, −1.6% vs. placebo, −1.4% (not statistically different)]. Pioglitazone also significantly increased high‐density lipoprotein cholesterol levels [adjusted mean difference: +4.5 (95% CI: 2.6–6.5) mg/dl], decreased triglyceride levels [−43.9 (−69.2, −18.6) mg/dl], shifted low‐density lipoprotein (LDL) particle concentrations from small [pattern B, −13.6% (−17.7%, −9.5%)] to large [pattern A, +15.1% (10.8%, 19.5%)] and increased mean LDL particle size [+3.8 (2.6, 4.9) Å]. More pioglitazone‐treated patients experienced oedema (9.0 vs. 4.5%) and weight gain (9.1 vs. 2.7%) than placebo patients. Conclusions: Pioglitazone in combination with insulin therapy improved glycaemic control, reduced insulin dose requirements and improved lipid profiles in patients with type 2 diabetes previously poorly controlled with combination therapy.