'Human' insulin versus animal insulin in people with diabetes mellitus

 

Abstract

Background

Human insulin was introduced for the routine treatment of diabetes mellitus in the early 1980s without adequate comparison of efficacy to animal insulin preparations. First reports of altered hypoglycaemia awareness after transfer to human insulin made physicians and especially patients uncertain about potential adverse effects of human insulin.

Objectives

To assess the effects of different insulin species by evaluating their efficacy (in particular glycaemic control) and adverse effects profile (mainly hypoglycaemia).

Search methods

A highly sensitive search for randomised controlled trials combined with key terms for identifying studies on human versus animal insulin was performed using The Cochrane Library, MEDLINE and EMBASE. We also searched reference lists and databases of ongoing trials.

Selection criteria

We included randomised controlled clinical trials with diabetic patients of all ages that compared human to animal (for the most part purified porcine) insulin. Trial duration had to be at least one month in order to achieve reliable results on the main outcome parameter glycated haemoglobin.

Data collection and analysis

Trial selection as well as evaluation of study quality was performed by two independent reviewers. The quality of reporting of each trial was assessed according to a modification of the quality criteria as specified by Schulz and by Jadad.

Main results

Altogether 2156 participants took part in the 45 randomised controlled studies that were discovered through extensive search efforts. Though many studies had a randomised, double-blind design, most studies were of poor methodological quality. Purified porcine and semi-synthetic insulin were most often investigated. No significant differences in metabolic control or hypoglycaemic episodes between various insulin species could be elucidated. Insulin dose and insulin antibodies did not show relevant dissimilarities.

Authors' conclusions

A comparison of the effects of human and animal insulin as well as of the adverse reaction profile did not show clinically relevant differences. Many patient-oriented outcomes like health-related quality of life or diabetes complications and mortality were never investigated in high-quality randomised clinical trials. The story of the introduction of human insulin might be repeated by contemporary launching campaigns to introduce pharmaceutical and technological innovations that are not backed up by sufficient proof of their advantages and safety.

 

Plain language summary

'Human' insulin versus animal insulin in people with diabetes mellitus

Human insulin has become the insulin of choice for newly diagnosed patients with diabetes mellitus. Insulin companies are eventually not going to maintain different species formulations for a declining proportion of the population with diabetes using animal insulin. Concerns exist about increased hypoglycaemia following transfer to human insulin and availability of animal insulin especially in developing countries. In our systematic review we could not identify substantial differences in the safety and efficacy between insulin species. Many important patient-oriented outcomes like health-related quality of life and effects on diabetic complications and mortality were never investigated. Human insulin was introduced into the market without scientific proof of advantage over existing purified animal insulins, especially porcine insulin.

 

摘要

背景

人類胰島素及動物胰島素使用在糖尿病人之比較

人類胰島素於1980年代早期使用於糖尿病人的治療，它的療效未與動物胰島素做足夠的比較。首批報告指出轉換成人類胰島素會使得病人對低血糖的警覺改變，而這使得醫生，尤其是病人對人類胰島素可能的副作用產生不確定感。

目標

評估不同種類的胰島素其效益(主要是血糖控制)及副作用(主要是低血糖)。

搜尋策略

利用Cochrane Library, MEDLINE及EMBASE等高度敏感的搜尋，針對隨機有控制組的試驗併隨關鍵詞來找尋人類及動物胰島素相關的研究。我們並且搜尋參考項目及正在進行試驗的database，最近搜尋日期：2004年7月

選擇標準

我們納入隨機且有控制組的臨床試驗，針對各種年齡層的糖尿病人比較人類及動物(大部份是純化的豬)胰島素，試驗其間至少一個月，為了需取得可信賴的結論，主要結果變數為糖化血色素。

資料收集與分析

試驗的選擇及研究品質的評估，由二位獨立的審核者進行。每一篇試驗的品質報告根據Schulz 及 Jadad所修正出來的品質標準。

主要結論

全面搜尋後，總共有2156受試者參與45篇隨機且具控制組的研究。雖然很多的研究有隨機隻盲設計，大部份的研究方法不是很好，純豬的胰島素或半合成的胰島素最常被探討，各種胰島素在代謝控制或低血糖發生無差別意義，胰島素劑量及胰島素抗體無顯示相關的相異性。

作者結論

比較人類及動物胰島素的效益及引起的副作用，臨床上顯示不出有相關的差異性，很多以病人為主的結果，像生活的健康相關品質或糖尿病併發症及死亡率方面，在這些品質好的隨機臨床試驗未看到。人類胰島素的引進歷史，被當代的活動一直重複述說其藥學或為科技的新發明。而在益處及安全性卻少著墨。

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

人類及純化的動物(主要是豬)胰島素在效益及副作用無相關的差異，人類胰島素成為新診斷的糖尿病人首選的胰島素製劑。胰島素製造公司原則上並不打算維持各種不同的配方，因為糖尿病人使用動物胰島素有下降的趨勢，要關心的是轉換成人類胰島素所增加的低血糖及發展中國家動物胰島素的有效利用性。在我們系統性的回顧，我們不能發現在各種胰島素製劑其安全及有效性有實質的差異。最主要的是以病人為主的結果，如健康相關的生活品質及對糖尿病併發症的效益及死亡率未被研究。人類胰島素被引進市場，沒有經過科學証明其比現存的純化動物胰島素有好處，尤其是豬胰島素。