Metformin added to insulin therapy for type 1 diabetes mellitus in adolescents

 

Abstract

Background

In adolescents with type 1 diabetes, insulin resistance likely plays a role in the deterioration of metabolic control. In type 1 diabetes, addition of metformin to insulin therapy, to improve insulin sensitivity, has been assessed in a few trials involving few patients or in uncontrolled studies of short duration. No systematic reviews are available up to date to summarize the evidence about metformin addition to insulin therapy in adolescents with type 1 diabetes.

Objectives

To assess the effects of metformin added to insulin therapy for type 1 diabetes mellitus in adolescents.

Search methods

We searched The Cochrane Library, MEDLINE and EMBASE. We also searched databases of ongoing trials, reference lists of relevant reviews, and we contacted experts, authors and manufacturers.

Selection criteria

Any randomised controlled trial (RCT) of at least three months duration of treatment comparing metformin added to insulin therapy versus insulin therapy alone in adolescents with type 1 diabetes was included. Cross-over and quasi-randomised controlled trials were excluded.

Data collection and analysis

Two reviewers read all abstracts, assessed quality and extracted data independently. Authors were contacted for missing data.

Main results

Only two trials (60 participants) investigating the effect of metformin added to insulin therapy for three months in adolescents with poorly controlled type 1 diabetes could be included. Meta-analysis was not possible due to the clinical and methodological heterogeneity of data. Both studies suggested that metformin treatment lowered glycosylated haemoglobin A1c (HbA1c) in adolescents with type 1 diabetes and poor metabolic control. Improvements in insulin sensitivity, body composition or serum lipids were not documented in either study, however, one study showed a decrease in insulin dosage by 10%. Adverse effects were mainly gastrointestinal in both studies and hypoglycaemia in one study. No data on health-related quality of life, all-cause mortality or morbidity are currently available.

Authors' conclusions

There is some evidence suggesting improvement of metabolic control in poorly controlled adolescents with type 1 diabetes, on addition of metformin to insulin therapy. Stronger evidence is required from larger studies, carried out over longer time periods to document the long-term effects on metabolic control, health-related quality of life as well as morbidity and mortality in those patients.

 

Plain language summary

Metformin added to insulin therapy for type 1 diabetes mellitus in adolescents

Diabetes mellitus is a metabolic disorder resulting from a defect in insulin secretion, insulin action, or both. Metabolic control (glycaemic control, that is long-term blood glucose levels as measured by glycosylated haemoglobin A1c (HbA1c)) often deteriorates during puberty in children with type 1 diabetes possibly due to the development of insulin resistance (insulin does not work effectively in the tissues anymore) and this creates a great need for alternative therapeutic strategies in those patients. We searched for randomised controlled trials of good quality that studied the effects of metformin added to insulin therapy for type 1 diabetes mellitus in adolescents on glycaemic control, insulin sensitivity, health-related quality of life, side-effects as well as effects on body weight, serum lipids and insulin dose.
Only two trials (60 participants, three months treatment) could be included. Both studies suggested that metformin plus insulin treatment lowered HbA1c somewhat more than placebo plus insulin. Improvement in insulin sensitivity, body weight or serum lipids were not seen in either study. However, one study showed a small decrease in insulin dosage by 10%. Side effects were mainly gastrointestinal upset in both studies and hypoglycaemia (low blood sugar) in one study. There was no information on health-related quality of life, costs, morbidity or mortality in either study.

 

摘要

背景

Metformin合併胰島素對第一型糖尿病青少年的治療成效

對第一型糖尿病青少年來說,胰島素阻抗是血糖控制惡化的重要原因之一.在這類病人,合併胰島素及metformin的治療來增加身體胰島素敏感性,已經有一些臨床試驗正在進行,但病人數太少或是缺少對照組且試驗時間太短.但是目前為止仍然沒有一個系統性的回顧針對metformin合併胰島素對於第一型糖尿病年輕人的治療成效提出結論.

目標

為了評估metformin合併胰島素對於第一型糖尿病青少年的治療成效

搜尋策略

我們搜尋了The Cochrane Library, MEDLINE以及EMBASE資料庫.我們同時也搜尋了正在進行中的試驗資料,相關文獻,並詢問相關專家作者及藥品製造商的意見

選擇標準

任何隨機控制,比較metformin合併胰島素及單純使用胰島素在治療第一型糖尿病年輕人的成效,時間持續三個月以上的試驗,都將他納入這次的回顧當中.交叉試驗或是quasirandomised controlled trials則被排除.

資料收集與分析

由兩位審查者各自獨立地閱讀所有的摘要,評估試驗品質與擷取其中的資料,如果資料有遺失的部分,則連絡作者以取得相關資料.

主要結論

只有兩個實驗(60位受試者),針對控制不佳的第一型糖尿病青少年,採用metformin合併胰島素的治療評估三個月的時間,被納入這次的回顧當中.由於臨床與方法學上的差異,我們無法進行資料的交叉分析.但是兩個研究都指出,針對血糖控制不佳的第一型糖尿病青少年,合併metformin治療可以有效減低醣化血色素(HbA1c)的數值.但是針對胰島素敏感性,身體成分組成或血脂濃度的變化,則沒有明確的結論.但是有一個試驗指出,採用這種治療方式,可以有效減少胰島素使用量達10%.副作用大部分都是腸胃道症狀,其中一個試驗則有病患出血低血糖的情形.至於健康相關的生活品質,死亡率,其他併發症發病率等目前都沒有相關的資料.

作者結論

目前有部分的證據顯示合併metformin及胰島素,可以改善血糖控制不良的第一型糖尿病青少年的代謝指標.但是仍需要更多的實驗,更長的追蹤時間,來提供更強的證據證明長期控制的效果,以及對生活品質,死亡率,以及併發症的影響.

翻譯人

本摘要由臺灣大學附設醫院高玉禧翻譯。

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

總結

Metformin合併胰島素對第一型糖尿病青少年 的治療成效:糖尿病是一種代謝性的疾病,導因於胰島素分泌的缺陷,胰島素作用的異常,或兩者皆有.血糖控制(長期血糖控制的結果是依據醣化血色素的值作為評估依據)通常隨著第一 型糖尿病童進入青春期而惡化,可能歸因於胰島素阻抗的產生(指的是胰島素在組織中無法有效的發揮作用),這樣的狀況也導致必須使用更多的治療方式來治療這類病患.我們搜尋了相關的隨機控制試驗,針對第一型糖尿病病患合併metformin以及胰島素治療,對於血糖控制,胰島素敏感性,相關生活品質,副作用,體重,血脂,和胰島素劑量的影響作一個統計.只有兩個實驗(60位病患接受三個月的治療)被納入我們的回顧當中,兩個實驗都建議採用這類的合併治療比安慰劑更能有效減少醣化血色素的數值.胰島素敏感性的增加,體重改變或是血脂濃度則沒有很好的結論,但是其中一個實驗指出,胰島素用量因此減少了10%.副作用的部分主要來自腸胃道的不適,其中一個實驗則有病患出現低血糖的症狀.至於與健康相關的生活品質,死亡率,併發症等,則沒有相關的資料.