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每日一次的地特胰岛素对2型糖尿病患者口服抗糖尿病药物(OAD)使用的影响。

Effect of once-daily insulin detemir on oral antidiabetic drug (OAD) use in patients with type 2 diabetes.

作者信息

Vora J, Caputo S, Damci T, Orozco-Beltran D, Pan C, Svendsen A L, Sølje K S, Khunti K

机构信息

Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Liverpool, UK.

出版信息

J Clin Pharm Ther. 2014 Apr;39(2):136-43. doi: 10.1111/jcpt.12116. Epub 2013 Dec 13.

Abstract

WHAT IS KNOWN AND OBJECTIVE

There are acknowledged benefits to continuing metformin when initiating insulin, but there appears to be growing concern over the role of sulphonylureas and thiazolidinediones when used in combination with insulin. This analysis investigates the effects of continuing or discontinuing oral antidiabetic drugs (OADs) following the initiation of once-daily insulin detemir.

METHODS

SOLVE is a 24-week, multinational observational study of insulin detemir initiation in patients with type 2 diabetes mellitus treated with one or more OADs.

RESULTS

In the total cohort (n = 17 374), there were significant improvements in HbA1c (-1·3%, 95% CI -1·34; -1·27%) and weight (-0·6 kg, 95% CI -0·65; -0·47 kg), with an increase in the incidence rate of minor hypoglycaemia (+0·256 events ppy, P < 0·001), but not severe hypoglycaemia (-0·038 events ppy, P < 0·001). Study participants had information on OAD use either prior to (n = 17 086) or during insulin initiation (n = 16 346). HbA1c reductions were significantly greater in patients continuing treatment with metformin (-1·3% vs. -1·1%, P < 0·01), thiazolidinediones (-1·3% vs. -1·0%, P < 0·01) and DPP-IV inhibitors (-1·3% vs. -0·9%, P < 0·001). Final insulin doses were significantly greater in patients discontinuing treatment with sulphonylureas (0·29 vs. 0·26 IU/kg, P < 0·001), glinides (0·28 vs. 0·26 IU/kg, P < 0·01), thiazolidinediones (0·31 vs. 0·26 IU/kg, P < 0·001) and DPP-IV inhibitors (0·35 vs. 0·29 IU/kg, P < 0·001) compared with patients continuing these respective agents. All patient subgroups had a mean weight loss irrespective of OAD continuation, apart from those continuing thiazolidinediones (+0·2 kg). The largest improvements in weight were seen following the withdrawal of sulphonylureas and thiazolidinediones (-1·1 and -1·1 kg, respectively).

WHAT IS NEW AND CONCLUSION

Discontinuation (or switching) of OADs at the time of insulin initiation appears to be governed principally by concerns about hypoglycaemia and weight. HbA1c improvements were smaller in patients discontinuing OADs at the time of insulin initiation and may be associated with insufficient insulin titration.

摘要

已知信息与研究目的

在开始使用胰岛素时继续使用二甲双胍有公认的益处,但磺脲类药物和噻唑烷二酮类药物与胰岛素联合使用时,人们对其作用的担忧似乎日益增加。本分析调查了开始每日一次地特胰岛素治疗后继续或停用口服降糖药(OADs)的效果。

方法

SOLVE是一项为期24周的多国观察性研究,观察在接受一种或多种OADs治疗的2型糖尿病患者中开始使用地特胰岛素的情况。

结果

在整个队列(n = 17374)中,糖化血红蛋白(HbA1c)(-1.3%,95%置信区间-1.34;-1.27%)和体重(-0.6 kg,95%置信区间-0.65;-0.47 kg)有显著改善,轻度低血糖发生率增加(+0.256次/人年,P < 0.001),但严重低血糖发生率未增加(-0.038次/人年,P < 0.001)。研究参与者在开始使用胰岛素之前(n = 17086)或期间(n = 16346)有关于OADs使用的信息。继续使用二甲双胍(-1.3%对-1.1%,P < 0.01)、噻唑烷二酮类药物(-1.3%对-1.0%,P < 0.01)和二肽基肽酶-4(DPP-IV)抑制剂(-1.3%对-0.9%,P < 0.001)治疗的患者,HbA1c降低幅度显著更大。与继续使用这些药物的患者相比,停用磺脲类药物(0.29对0.26 IU/kg,P < 0.001)、格列奈类药物(0.28对0.26 IU/kg,P < 0.01)、噻唑烷二酮类药物(0.31对0.26 IU/kg,P < 0.001)和DPP-IV抑制剂(0.35对0.29 IU/kg,P < 0.001)的患者,最终胰岛素剂量显著更高。除了继续使用噻唑烷二酮类药物的患者(+0.2 kg)外,并无论OADs是否继续使用,所有患者亚组的体重均有平均下降。停用磺脲类药物和噻唑烷二酮类药物后体重改善最大(分别为-1.1和-1.1 kg)。

新发现与结论

在开始使用胰岛素时停用(或更换)OADs似乎主要受低血糖和体重问题的影响。在开始使用胰岛素时停用OADs的患者,HbA改善较小,可能与胰岛素滴定不足有关。

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