Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus

  • Review
  • Intervention

Authors


Abstract

Background

It is unclear whether patients with type 2 diabetes who have poor glycaemic control despite maximal oral hypoglycaemic agents (OHAs) should be commenced on insulin as monotherapy, or insulin combined with oral hypoglycaemic agents (insulin-OHA combination therapy).

Objectives

To assess the effects of insulin monotherapy versus insulin-OHA combinations therapy.

Search methods

Eligible studies were identified by searching MEDLINE, EMBASE, and The Cochrane Library.

Selection criteria

Randomised controlled trials (RCTs) with 2 months minimum follow-up duration comparing insulin monotherapy (all schemes) with insulin-OHA combination therapy.

Data collection and analysis

Data extraction and assessment of study quality were undertaken by three reviewers in pairs.

Main results

Twenty RCTs (mean trial duration 10 months) including 1,811 participants, with mean age 59.8 years and mean known duration of diabetes 9.6 years. Overall, study methodological quality was low. Twenty-eight comparisons in 20 RCTs were ordered according to clinical considerations. No studies assessed diabetes-related morbidity, mortality or total mortality. From 13 studies (21 comparisons), sufficient data were extracted to calculate pooled effects on glycaemic control. Insulin-OHA combination therapy had statistically significant benefits on glycaemic control over insulin monotherapy only when the latter was applied as a once-daily injection of NPH insulin. Conversely, twice-daily insulin monotherapy (NPH or mixed insulin) provided superior glycaemic control to insulin-OHA combination therapy regimens where insulin was administered as a single morning injection. In more conventional comparisons, regimens utilising OHAs with bedtime NPH insulin provided comparable glycaemic control to insulin monotherapy (administered as twice daily, or multiple daily injections). Overall, insulin-OHA combination therapy was associated with a 43% relative reduction in total daily insulin requirement compared to insulin monotherapy. Of the 14 studies (22 comparisons) reporting hypoglycaemia, 13 demonstrated no significant difference in the frequency of symptomatic or biochemical hypoglycaemia between insulin and combination therapy regimens. No significant differences in quality of life related issues were detected. Combination therapy with bedtime NPH insulin resulted in statistically significantly less weight gain compared to insulin monotherapy, provided metformin was used ± sulphonylurea. In all other comparisons no significant differences with respect to weight gain were detected.

Authors' conclusions

Bedtime NPH insulin combined with oral hypoglycaemic agents provides comparable glycaemic control to insulin monotherapy and is associated with less weight gain if metformin is used.

摘要

背景

第2型糖尿病人使用單一胰島素治療或口服降血糖藥物併胰島素治療的比較

第2型糖尿病人使用最大劑量口服降血糖藥物,其血糖仍控制不佳病人,是否建議胰島素單一治療,或使用胰島素合併口服降血糖藥物治療仍未明確

目標

評估胰島素單一療法及胰島素口服降血糖藥物療法的效果

搜尋策略

搜尋MEDLINE,EMBASE,and The Cochrane Library,找出適當的研究,最近搜尋日:2004年5月

選擇標準

隨機控制試驗RCTs,而且最少追蹤二個月,來比較胰島素單一療法及胰島素口服降血糖藥合併療法

資料收集與分析

資料收集與論文品質分析經由三位配對的評論者完成

主要結論

20篇隨機控制試驗(平均試驗期間10個月)包含1811參與者,平均年齡59.8歲,其平均已知糖尿病9.6年,總而言之,研究方法品質是低的。這20篇隨機控制試驗的28種對照(comparisons)都是依照臨床上的考量,沒有研究探討糖尿病相關的罹病率、死亡率或全部疾病的死亡率。充分的資料從13篇研究(21種對照)篩選出來計算血糖控制的全部效益。胰島素口服降血糖藥物合併療法比單一胰島素療法在血糖控制上有統計上的意義效益,如果後者只使用一天一次NPH胰島素注射。相反的,一天二次注射胰島素單一療法(NPH或混合式胰島素)比胰島素一口服降血糖藥物合併療法,而其胰島素是早晨單次注射,可提供較佳血糖控制。如依照更傳統的對照,使用口服降血糖藥物併睡前胰島素處方比單一胰島素療法(一天二次或一天多次注射)可提供可相比較的血糖控制。總而言之,胰島素一口服降血糖藥物比胰島素單一療法可降低相當43%整天胰島素使用量。14篇研究(22種對照)報告低血糖,13篇證實在胰島素單一或合併療法,其有症狀或僅有生化值的低血糖其頻率的差別是無意義的。有關生活品質相關的議題也是無意義差別。合併療法加睡前胰島素,只要併用metformin,比單一胰島素療法,在體重增加方面,統計上是有意義減少的。在其他對照中,體重增加方面差別是無意義的。

作者結論

睡前NPH胰島素併用口服降血糖藥物提供可與胰島素單一療法相比較的血糖控制,而且併用Metformin時,病人體重較少增加。

翻譯人

本摘要由慈濟醫院陳信典翻譯。

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

總結

單純使用每天一次胰島素注射併用口服降血糖藥物,可能可以促進第2型糖尿病人開始使用胰島素。這些回顧省視20篇試驗,包括1811受試者,來比較需打胰島素的第2型糖尿病人,使用單一胰島素或胰島素併用口服降血糖藥物,結論建議睡前NPH胰島素口服降血糖藥物併用療法,提供與單一胰島素可相比較的血糖控制。因為缺乏研究,所以胰島素口服降血糖藥Metformin 併用是否優於Metformin加sulphonylurea仍不清楚。大部分的病例,胰島素單一或併用口服降血糖藥,其低血糖事件無有意義的差異。沒有研究評估糖尿病相關的罹病率及死亡率。

Plain language summary

Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus

Simple application of a single daily insulin injection in addition to oral hypoglycaemic agents may facilitate the initiation of insulin therapy in type 2 diabetes mellitus.This review examined 20 trials including 1,811 participants which compared insulin monotherapy with insulin in combination with oral hypoglycaemic agents (OHA) in insulin-requiring patients with type 2 diabetes. The results suggest that a bedtime NPH insulin-oral hypoglycaemic agent combination therapy regimen provides comparable glycaemic control to insulin monotherapy. Due to lack of studies it remains unclear whether insulin-OHA combination regimens with metformin alone are superior to those with metformin plus a sulphonylurea. In most cases no significant differences in hypoglycaemic events were observed between insulin mono- and OHA combination therapy. No study assessed diabetes-related morbidity or mortality.

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