Meglitinide analogues for type 2 diabetes mellitus

 

Abstract

Background

In type 2 diabetes mellitus, impairment of insulin secretion is an important component of the disease. Meglitinide analogues are a class of oral hypoglycaemic agents that increase insulin secretion, in particular, during the early phase of insulin release.

Objectives

The aim of this review was to assess the effects of meglitinide analogues in patients with type 2 diabetes mellitus.

Search methods

We searched several databases including The Cochrane Library, MEDLINE and EMBASE. We also contacted manufacturers and searched ongoing trials databases, and the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) web sites.

Selection criteria

We included randomised controlled, parallel or cross-over trials comparing at least 10 weeks of treatment with meglitinide analogues to placebo, head-to-head, metformin or in combination with insulin.

Data collection and analysis

Two authors independently extracted data and assessed trial quality.

Main results

Fifteen trials involving 3781 participants were included. No studies reported the effect of meglitinides on mortality or morbidity. In the eleven studies comparing meglitinides to placebo, both repaglinide and nateglinide resulted in a reductions in glycosylated haemoglobin (0.1% to 2.1% reduction in HbA1c for repaglinide; 0.2% to 0.6% for nateglinide). Only two trials compared repaglinide to nateglinide (342 participants), with greater reduction in glycosylated haemoglobin in those receiving repaglinide. Repaglinide (248 participants in three trials) had a similar degree of effect in reducing glycosylated haemoglobin as metformin. Nateglinide had a similar or slightly less marked effect on glycosylated haemoglobin than metformin (one study, 355 participants). Weight gain was generally greater in those treated with meglitinides compared with metformin (up to three kg in three months). Diarrhoea occurred less frequently and hypoglycaemia occurred more frequently but rarely severely enough as to require assistance.

Authors' conclusions

Meglitinides may offer an alternative oral hypoglycaemic agent of similar potency to metformin, and may be indicated where side effects of metformin are intolerable or where metformin is contraindicated. However, there is no evidence available to indicate what effect meglitinides will have on important long-term outcomes, particularly mortality.

 

Plain language summary

Meglitinide analogues for type 2 diabetes mellitus

In type 2 diabetes mellitus, impairment of insulin secretion is an important component of the disease. The meglitinide analogues ("meglitinides") are a class of oral antidiabetic agents that increase insulin secretion in the pancreas. The properties of this class of drug suggest that they have the potential to produce a rapid, short-lived insulin output. Two analogues are currently available for clinical use: repaglinide and nateglinide. Altogether 15 studies were included in this review, eight of the studies used repaglinide as the study drug and five used nateglinide. Two compared the two meglitinides to one another. In total, 3781 people participated in the 15 studies which mainly lasted between 10 and 24 weeks (one study had a duration of 52 weeks).
No studies reported the effect of meglitinides on mortality or diabetes related complications. In the eleven studies comparing meglitinides to placebo, both repaglinide and nateglinide resulted in an improved blood sugar control. Weight gain was generally greater in those treated with meglitinides compared with metformin (up to three kg in three months), another oral antidiabetic drug. Here, diarrhoea occurred less frequently and hypoglycaemia occurred more frequently but rarely severely enough as to require assistance.
Meglitinides may offer an alternative oral hypoglycaemic agent of similar potency to metformin, and may be indicated where side effects of metformin are intolerable (in particular persistent diarrhoea) or where metformin is contraindicated. However, there is no evidence available yet to indicate what effect meglitinides will have on important long-term outcomes, in particular, on mortality. As yet, the experience with meglitinides in terms of side effects is limited. Results from other Cochrane review groups may provide additional information about the potential role of meglitinides in the management of type 2 diabetes mellitus.

 

摘要

背景

Meglitinide analogues 對於第二型糖尿病之作用

胰島素分泌不足是第二型糖尿病一個重要的病因。Meglitinide analogues 這類的口服降血糖藥可以增加胰島素的分泌，尤其是在胰島素分泌的早期。

目標

本文希望評估Meglitinide analogues 對於第二型糖尿病患的療效。

搜尋策略

我們搜尋包括The Cochrane Library、MEDLINE、及EMBASE等資料庫。我們也連繫了藥廠,找尋目前正在進行中的試驗以及American Diabetes Association(ADA)及European Association for the study of Diabetes(EASD)等網站。

選擇標準

我們納入隨機控制的平行或交叉試驗. 這些試驗進行至少十週以上,比較meglitinide analogues 與安慰劑,其他同類藥, metformin 或合併胰島素的療效差異。

資料收集與分析

由兩個獨立作業的作者來選取資料及評估試驗的品質。

主要結論

總共選了15個試驗包含了3781個參與者。沒有研究報告meglitinides對於死亡率或併發症的影響。在11個比較meglitinides及安慰組的試驗中,研究結果顯示repaglinide及nateglinide可使糖化血色素下降(repaglinide組糖化血色素下降0.1％到2.1％，nateglinide組糖化血色素下降0.2％到0.6％)。只有兩個試驗比較了repaglinide及nateglinide(共342個參與者)，顯示在使用repaglinide組在下降糖化血色素方面有較好的效果。Repaglinide(3個試驗，共有248個參與者)在降糖化血色素的程度與metformin相似. Nateglinide (一個試驗,355位參與者)在降糖化血色素的程度與metformin相似或稍差。使用Meglitinides組體重上升的程度比使用metformin組來得高(最高在3個月內可增加3公斤)。副作用方面少見腹瀉，低血糖發生的頻率比較多，不過很少嚴重到需要額外的治療。

作者結論

Meglitinide是一項可供選擇的降血糖的藥物，降血糖的效果與metformin相近，因此當病人對metformin的副作用無法忍受或有禁忌症時可以考慮使用。然而，沒有證據顯示meglitinides對於長期預後(特別是死亡率)有什麼影響。

翻譯人

本摘要由臺灣大學附設醫院賴瑩純翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

Meglitinide是一項可供選擇的降血糖藥物，與metformin相近，不過對於長期預後的影響仍不明確。在第二型糖尿病患者，胰島素分泌不足是一項重要的病因。 Meglitinide analogues(也就是meglitinides)是可以增加胰島素分泌的口服降血糖藥。這類藥物的特色是能夠產生快速、短效的胰島素輸出。目前有兩種Meglitinide analogues可以使用：repaglinide及nateglinide。這篇文章選用了15個研究，其中8個研究使用repaglinide當作試驗藥，5個研究使用nateglinide當作試驗藥。有二個研究比較這兩個meglitinides藥物。全部共選了15個試驗包含3781個參與者，追蹤時間至少10到24週(最長的一個研究為五十二週)。沒有研究報告meglitinides對於死亡率或糖尿病相關併發症的影響。在11個比較meglitinides及安慰組的研究中顯示repaglinide及nateglinide可使糖化血色素下降。在使用Meglitinides組體重上升的程度比使用另一個降血糖藥metformin來得高(最高在三個月內可增加三公斤)。研究結果發現腹瀉頻率少，低血糖的發生率則比較多，不過都很少嚴重到需要額外的治療。因此，Meglitinide是一項可供選擇的降血糖藥物，降血糖的效果與metformin相近，因此當病人對metformin的副作用無法忍受或有禁忌症時可以考慮使用。然而,目前沒有確實的証據顯示meglitinides對於長期預後(尤其是死亡率)有重要的影響,有關它的副作用也所知有限.其它的Cochrane review groups的結論也許能提供meglitinides在處理第二型糖尿病患者的角色上額外的資訊。