Intervention Review

Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus

  1. Karl Horvath1,*,
  2. Klaus Jeitler1,
  3. Andrea Berghold2,
  4. Susanne H Ebrahim3,
  5. Thomas W Gratzer4,
  6. Johannes Plank1,
  7. Thomas Kaiser5,
  8. Thomas R Pieber1,
  9. Andrea Siebenhofer6

Editorial Group: Cochrane Metabolic and Endocrine Disorders Group

Published Online: 18 APR 2007

Assessed as up-to-date: 10 DEC 2006

DOI: 10.1002/14651858.CD005613.pub3

How to Cite

Horvath K, Jeitler K, Berghold A, Ebrahim SH, Gratzer TW, Plank J, Kaiser T, Pieber TR, Siebenhofer A. Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD005613. DOI: 10.1002/14651858.CD005613.pub3.

Author Information

  1. 1

    Medical University of Graz, Department of Internal Medicine, Graz, Austria

  2. 2

    Medical University of Graz, Institute for Medical Informatics, Statistics and Documentation, Graz, Austria

  3. 3

    Institute for Quality and Efficiency in Health Care, Cologne, Germany

  4. 4

    Medical University Graz, Department of Internal Medicine, Graz, Austria

  5. 5

    IQWiG, Koln, Germany

  6. 6

    Medical University of Graz, Department of Internal Medicine and Institute for Medical Informatics, Statistics and Documentation, Graz, Austria

*Karl Horvath, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, 8036, Austria.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 18 APR 2007




  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 摘要


Despite indications from epidemiological trials that higher blood glucose concentrations are associated with a higher risk for developing micro- and macrovascular complications, evidence for a beneficial effect of antihyperglycaemic therapy in patients with type 2 diabetes mellitus is conflicting. Two large studies, the United Kingdom Prospective Diabetes Study (UKPDS) and the University Group Diabetes Program (UGDP), did not find a reduction of cardiovascular endpoints through improvement of metabolic control. The theoretical benefits of newer insulin analogues might result in fewer macrovascular and microvascular events.


To assess the effects of long-term treatment with long-acting insulin analogues (insulin glargine and insulin detemir) compared to NPH insulin in patients with type 2 diabetes mellitus.

Search methods

Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library and communication with experts in the field as well as insulin producing companies.

Selection criteria

Studies were included if they were randomised controlled trials in adults with diabetes mellitus type 2 and had a trial duration of at least 24 weeks.

Data collection and analysis

Two authors independently assessed trial quality and extracted data. Pooling of studies by means of random-effects meta-analyses was performed.

Main results

Six studies comparing insulin glargine to NPH (Neutral Protamine Hagedorn) insulin and two studies comparing insulin detemir to NPH insulin were identified. In these trials, 1715 patients were randomised to insulin glargine and 578 patients to insulin detemir. Duration of the included trials ranged from 24 to 52 weeks. Metabolic control, measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint, and adverse effects did not differ in a clinical relevant way between treatment groups. While no statistically significant difference for severe hypoglycaemia rates was shown in any of the trials, the rate of symptomatic, overall and nocturnal hypoglycaemia was statistically significantly lower in patients treated with either insulin glargine or detemir. No evidence for a beneficial effect of long-acting analogues on patient-oriented outcomes like mortality, morbidity, quality of life or costs could be obtained.

Authors' conclusions

Our analysis suggests, if at all only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2 treated with "basal" insulin regarding symptomatic nocturnal hypoglycaemic events. Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir.


Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 摘要

Long acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus

NPH (Neutral Protamine Hagedorn) insulin is the current standard for basal insulin in the blood glucose lowering therapy in people with type 2 diabetes mellitus. The mode of action of this insulin is highly variable, which may be the cause for the difficulties some people with diabetes have to achieve current goals for long-term metabolic control. Therefore, new insulins which are thought to show more favourable properties of action have been developed: insulin glargine and insulin detemir. Because of their theoretical advantages, it is thought that treatment with these new insulin analogues might lead to a beneficial effect, for example less hypoglycaemia or a better metabolic control, possibly resulting in higher quality of life and treatment satisfaction less late diabetic complications such as problems with eyes, kidneys or feet and myocardial infarction, stroke or death.
Although epidemiological studies indicate that high concentrations of blood glucose carry a higher risk for these late complications, evidence for a beneficial effect of glucose-lowering therapy is conflicting. Following from the different results of large clinical trials, interventions seem to carry different substance specific beneficial or adverse effects. As a consequence, conclusions on the effects of different blood glucose lowering interventions on these outcomes can not be drawn from their effect on blood glucose concentration alone.
Methodological quality of all the studies was rated low ("C"). Eight studies investigated altogether 2293 people. Trials lasted between 24 and 52 weeks. Our analysis of the currently available long-term trials comparing long acting insulin analogues with NPH insulin showed that insulin glargine and insulin detemir were almost identically effective compared to NPH insulin in long-term metabolic control (HbA1c). Fewer people experienced symptomatic overall or nocturnal hypoglycaemic episodes with treatment with either of the two analogues. No conclusive information on late complications or on possible differences in the number of fatalities exists. For insulin glargine one study found a higher rate of progression of diabetic retinopathy in patients treated with insulin glargine, while in another investigation the opposite result was found. It was thus not possible to conclude for certain whether insulin glargine treatment is safe or not. From the retrieved trials it was also not possible to draw firm conclusions on the effects of these new insulins on quality of life or their cost effectiveness. Until long-term data on benefit and risk are available, we suggest a cautious approach to treatment with insulin glargine or insulin detemir.



  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 摘要



血糖値が高ければ高いほど、微小血管および大血管の合併症の発現リスクが高くなることが疫学研究から示唆されているにもかかわらず、2型糖尿病患者に対する抗高血糖療法の有益効果についてのエビデンスは相反している。2件の大規模な研究のUnited Kingdom Prospective Diabetes Study(UKPDS)とUniversity Group Diabetes Program(UGDP)では、代謝コントロールの改善を通しての心血管エンドポイントの低下は認められなかった。新しいインスリンアナログの理論上の利益は、大血管および微小血管のイベントが少なくなるようである。










インスリングラルギンとNPH(Neutral Protamine Hagedorn)インスリンを比較した研究6件およびインスリンデテミルとNPHインスリンを比較した研究2件を同定した。これらの試験において、患者1715例がインスリングラルギンにランダム化され、患者578例がインスリンデテミルにランダム化された。選択した試験の試験期間の範囲は24~52週間であった。サロゲートエンドポイントとして糖化ヘモグロビンA1c(HbA1c)により評価された代謝コントロールおよび有害作用は、臨床に関連した方法において治療群の間で差はなかった。重度の低血糖率については、いずれの試験においても統計学的有意差は示されなかったが、症候性低血糖、総低血糖および夜間低血糖の発現率はインスリングラルギンまたはデテミルのいずれかを投与された患者で統計学的に有意に低かった。死亡率、罹病率、生活の質,費用などの患者志向型アウトカムに対する長時間作用型アナログの有益効果を示すエビデンスは得られなかった。




監  訳: 2007.7.18

実施組織: 厚生労働省委託事業によりMindsが実施した。

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  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 摘要







研究是從電腦搜尋MEDLINE, EMBASE, The Cochrane Library且與這方面的專家及胰島素生產商討論。




二位作者獨立分析試驗品質及數據篩選,研究的匯入用randomeffects metaanalyses。


6篇研究比較glargine胰島素與NPH(Neutral Protamine Hagedorn)胰島素,2篇研究比較detemir 胰島素及NPH胰島素。在這些隨機試驗中,1715病人參與glargine胰島素,578病人參與detemir 胰島素。這些試驗的期間,從24週至52週。糖化血色素(HbA1c)的量測為代謝控制的代替指標,各治療組其藥物副作用在臨床相關上無不同。在這些任何試驗中,嚴重的低血糖比率無統計意義上的差別,但在有症狀低血糖,包括所有及夜間低血糖比率,在使用glargine或detemir 胰島素,在統計上仍顯示有意義的降低。沒有證據顯示在使用長效的胰島素類似物,對病人的死亡率、罹病率、生活品質及醫療費用有所助益。


我們的分析建議,就夜間有症狀的低血糖發生事件而言,第2型糖尿病人使用長效,基礎的胰島素類似物充其量也只有少量臨床上的好處。我們建議直到看到長期及安全數據出現,否則使用glargine或detemir 胰島素仍要謹慎為之。



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


在大部分第二型糖尿病人使用長效型胰島素類似物治療,沒有明確的臨床效益,證實NPH(Neutral Protamine Hagedorn)胰島素是糖尿病人降血糖治療目前標準的基礎胰島素。這種胰島素的作用模式是高度的不穩定性。很可能是一些糖尿病人,其長期要達到目前所設定的代謝控制目標困難的原因。所以新的胰島素基於有更好的作用特性被開發出來:insulin glargine及insulin detemir。因為這理論上的好處,使用這些新的胰島素類似物治療可能有益處,例如較少的低血糖及較好的代謝控制,可能導致較好的生活品質及較少的晚期併發症的治療滿意,如較少的眼睛、腎臟或足部問題及心肌梗塞,中風或死亡。雖然流行病學的研究指出高血糖導致這些晚期併發症有較高的危險,對降血糖有效益的證據是有爭論的。從這些大型臨床研究不同的結果,介入治療似乎帶來不同的特別效益或副作用。因此,不同的降血糖介入治療,對效果的下結論,不能靠血糖的改善。這些研究其方法的品質列為低的(“C”)。八篇研究總共調查2293病人。試驗期間從24到52週。我們分析目前可利用的長期試驗,比較長效胰島素類似物及NPH胰島素,顯示insulin glargine及insulin detemir與NPH胰島素在長期的代謝控制是幾乎在效益上是可以匹配的。在使用這兩種類似物的其中一種,很少病人有症狀的低血糖,全天侯或夜間低血糖。對晚期的併發症無有結論的資訊,或對一些不幸事件的數字有可能差異存在。對於insulin glargine,一篇研究發現在使用insulin glargine,有較高比率的糖尿病視網膜病變進展,在另外的探討卻有相反的結果,所以對insulin glargine治療是安全或不安全,很難下肯定結論。下一肯定的結論也是不可能。直到長期的效益及危害數據出現,我們建議使用insulin glargine或insulin detemir要謹慎為之。