Earlier triple therapy with pioglitazone in patients with type 2 diabetes

被引:23
作者
Charpentier, G. [1 ]
Halimi, S. [2 ]
机构
[1] Ctr Hosp Sud Francilien, F-91106 Corbeil Essonnes, France
[2] CHU Grenoble, Serv Endocrinol & Diabetol, F-38043 Grenoble, France
关键词
glycaemic control; metformin; pioglitazone; sulphonylurea; triple therapy; HOMEOSTASIS MODEL ASSESSMENT; BETA-CELL FUNCTION; STABLE INSULIN THERAPY; DOUBLE-BLIND; GLYCEMIC CONTROL; PARALLEL-GROUP; ORAL-THERAPY; COMBINATION THERAPY; METABOLIC SYNDROME; CONTROLLED-TRIAL;
D O I
10.1111/j.1463-1326.2009.01055.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide. Methods This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA(1c)) < 6.5%] or titrated up to 45 mg (if HbA(1c) > 6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA(1c) (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-B) were calculated. Results Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA(1c) and -2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA(1c) level of < 8.5% achieved the HbA(1c) target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA(1c) level was >= 8.5%, 13% achieved the HbA(1c) target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group. Conclusions In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA(1c), FPG and surrogate measures of beta-cell function. Patients were more likely to reach target HbA(1c) levels (< 7.0%) with pioglitazone treatment if their baseline HbA(1c) levels were < 8.5%, highlighting the importance of early triple therapy.
引用
收藏
页码:844 / 854
页数:11
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