Intermediate acting versus long acting insulin for type 1 diabetes mellitus

 

Abstract

Background

Diabetes mellitus type 1 is a chronic disease with short and long term complications. Its goals of therapy are to eliminate the symptoms of hyperglycaemia, reduce the long term microvascular and macrovascular complications and allow the patients to achieve a normal life-style. Basal insulin replacement for insulin dependent patients can be achieved with either intermediate or long acting insulin preparations.

Objectives

To assess the effects of intermediate acting versus long acting insulin preparations for basal insulin replacement in type 1 diabetic patients.

Search methods

We searched MEDLINE, EMBASE and The Cochrane Library, as well as reference lists, databases of ongoing trials, and requests from authors of included trials.

Selection criteria

Randomised controlled trials, assessing long acting insulin preparations compared to intermediate acting insulin preparations, in type 1 diabetic patients.

Data collection and analysis

Two reviewers independently scanned the titles. Data were extracted and analysed accordingly.

Main results

Twenty-three randomised controlled trials were identified. A total of 3872 and 2915 participants in the intervention and in the control group, respectively, were analysed. The weighted mean difference (WMD) for the level of glycosylated haemoglobin was -0.08 (95% confidence interval (CI) -0.12 to -0.04) in favour of the long acting insulin arm. The WMD between the groups in fasting plasma and blood glucose levels was -0.63 (95% CI -0.86 to -0.40) and -0.86 (95% CI -1.00 to -0.72) in favour of the long acting insulins. The odds ratio for a patient on long acting insulin to develop any type of hypoglycaemia was 0.93 (95% CI 0.8 to 1.08) compared to that of a patient on intermediate acting insulins. The OR for severe hypoglycaemic episodes was 0.73 (95% CI 0.61 to 0.87), and 0.70 (95% CI of 0.63 to 0.79) for nocturnal episodes. The WMD between the long and intermediate insulin groups for hypoglycaemic events per 100 patient follow up days was -0.77 (95% CI -0.89 to -0.65), -0.0 (95% CI -0.02 to 0.02) and -0.40 (95% CI -0.45 to -0.34) for overall, severe, and nocturnal hypoglycaemic episodes. Weight gain was more prominent in the control group. No difference was noted in the quantity or quality of severe adverse events or deaths.

Authors' conclusions

Long acting insulin preparations seem to exert a beneficial effect on nocturnal glucose levels. Their effect on the overall diabetes control is clinically unremarkable. Their use as a basal insulin regimen for type 1 diabetes mellitus warrants further substantiation.

 

Plain language summary

Intermediate acting versus long acting insulin for type 1 diabetes mellitus

Diabetes mellitus type 1 is a chronic disease with short and long term complications. The treatment for this disease is insulin administration, with basal and bolus insulin preparations being its main stay. Neutral Protamine Hagedorn (NPH) insulin had previously been considered the standard of care for basal insulin replacement in blood glucose lowering for people with type 1 diabetes mellitus. Over the years, newer and longer acting insulins with a more physiological action profile became available: insulin ultralente, and later insulin glargine and insulin detemir. Their theoretical advantages lead to the thought of a beneficial effect on glucose level and rate of complications, such as very low levels of glucose or long term complications. The aim of this review was to assess whether this theoretical advantage is translated into real-life benefits, by comparing the effect of long acting insulins to intermediate acting insulins on diabetes control.
Twenty-three studies fulfilled our inclusion criteria with a total of 3872 and 2915 participants in the intervention and in the control group, respectively. The methodological quality of all the studies was rated intermediate to low. Trials duration was no longer than one year. The level of glycosylated haemoglobin, a marker of diabetes control, was lower in the long acting insulin group, but the observed difference was of doubtful clinical significance. Longer acting insulins were superior mostly in their nocturnal effect, which resulted in a lower level of fasting glucose levels and fewer episodes of nocturnal hypoglycaemia. No data on long term complications were available.
The currently available data can not substantiate conclusions on the benefits and risks of long acting insulins, and long-term data are of need.

 

摘要

背景

中效與長效胰島素治療第1型糖尿病之比較

第1型糖尿病是一種具有短期和長期併發症的慢性病。治療的目標在於消除高血糖的症狀，減少小血管和大血管病變的長期併發症，並使病人能具有正常的生活方式。不管是中效或長效的胰島素製劑，對於胰島素依賴患者而言都能達到補充基礎胰島素需求的目的。

目標

比較以中效及長效的胰島素製劑，提供第1型糖尿病患基礎胰島素需求之效果。

搜尋策略

我們搜尋了MEDLINE、EMBASE、The Cochrane Library、文獻之參考書目、正在進行的臨床試驗之資料庫，以及被選入文獻之作者的要求。

選擇標準

比較中效與長效胰島素對於第1型糖尿病療效之隨機對照實驗。

資料收集與分析

兩個審查者獨立評估文獻之標題，並從中擷取和分析資料。

主要結論

共找出二十三個隨機對照實驗，其中3872個受試者為實驗組，2915個受試者為對照組。長效胰島素組的糖化血色素較低，加權平均差(WMD)為−0.08 (95% CI −0.12－−0.04)，其空腹血漿與全血之血糖亦較低，加權平均差分別是−0.63 (95 % CI −0.86－0.40)和−0.86 (95 % CI −1.00－−0.72)。使用長效胰島素相對於中效胰島素造成之任何類型低血糖的odds ratio是 0.93 (95 % CI 0.8－1.08)。嚴重低血糖的odds ratio是0.73 (95 % CI 0.61－0.87)，而夜間發生之嚴重低血糖的odds ratio是0.70 (95 % CI 0.63－0.79)。每100個病人追蹤日中長效和中效胰島素造成的全部、嚴重及夜間低血糖事件的加權平均差分別是−0.77 (95 % CI −0.89－−0.65)、−0.0 (95 % CI −0.02－0.02)和−0.40 (95 % CI為−0.45－ −0.34)。實驗組的體重增加較明顯。兩組在嚴重不良反應或死亡事件的量與質上沒有差別。

作者結論

長效胰島素似乎在夜間血糖控制上有較多之益處。但其對整體的糖尿病控制則臨床效果不明顯。以長效胰島素作為第1型糖尿病的基礎胰島素之療法需要進一步的研究證實。

翻譯人

本摘要由慈濟醫院謝至鎠翻譯。

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

總結

第1型糖尿病是一種具有短期和長期併發症的慢性病。此一疾病需以胰島素治療，主要是使用長效的基礎胰島素與短效的追加劑量(bolus insulin)。中性魚精蛋白(NPH)胰島素以前是第1型糖尿病人降血糖所使用的基礎胰島素之標準製劑。這些年來，已有更符合生理功能的新型長效胰島素，包括insulin ultralente, insulin glargine以及insulin detemir可用。他們在理論上的優勢，可能有利於改善血糖控制及併發症率，如極低血糖之狀況或長期併發症。本回顧之目的是藉由比較長效與中效的胰島素製劑在控制血糖上之療效，以評估這種理論上的優點是否能轉為實際之益處。合乎納入條件的23篇研究中共有實驗組3872人與對照組2915人。所有論文的研究方法的品質均屬中或低等。研究之時間皆不超過一年。長效胰島素組之血糖控制指標，糖化血色素，較低，但其差異程度之臨床意義值得懷疑。長效胰島素主要因其夜間作用效果較佳，而使空腹血糖值較低且夜間低血糖發作次數減少。沒有關於長期併發症的資料。現有資料無法對長效胰島素好處或風險下結論，仍需長期的資料以資佐證。