Intervention Review

Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus

  1. Bernd Richter*,
  2. Elizabeth Bandeira-Echtler,
  3. Karla Bergerhoff,
  4. Christian Lerch

Editorial Group: Cochrane Metabolic and Endocrine Disorders Group

Published Online: 23 APR 2008

Assessed as up-to-date: 30 JAN 2008

DOI: 10.1002/14651858.CD006739.pub2


How to Cite

Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch C. Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD006739. DOI: 10.1002/14651858.CD006739.pub2.

Author Information

  1. Universitaetsklinikum Duesseldorf, Heinrich-Heine University, Department of General Practice, Duesseldorf, Germany

*Bernd Richter, Department of General Practice, Universitaetsklinikum Duesseldorf, Heinrich-Heine University, PO Box 101007, Duesseldorf, 40001, Germany. richterb@uni-duesseldorf.de.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 23 APR 2008

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

In type 2 diabetes mellitus there is a progressive loss of beta-cell function. One new approach yielding promising results is the use of the orally active dipeptidyl peptidase-4 (DPP-4) inhibitors like sitagliptin and vildagliptin.

Objectives

To assess the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus.

Search methods

Studies were obtained from computerised searches of MEDLINE, EMBASE and The Cochrane Library.

Selection criteria

Studies were included if they were randomised controlled trials in adult people with type 2 diabetes mellitus and had a trial duration of at least 12 weeks.

Data collection and analysis

Two authors independently assessed risk of bias and extracted data. Pooling of studies was performed by means of fixed-effect meta-analysis.

Main results

Twenty-five studies of good quality were identified, 11 trials evaluated sitagliptin and 14 trials vildagliptin treatment. Altogether, 6743 patients were randomised in sitagliptin and 6121 patients in vildagliptin studies, respectively. Sitagliptin and vildagliptin studies ranged from 12 to 52 weeks duration. No data were published on mortality, diabetic complications, costs of treatment and health-related quality of life.
Sitagliptin and vildagliptin therapy in comparison with placebo resulted in an HbA1c reduction of approximately 0.7% and 0.6%, respectively. Data on comparisons with active comparators were limited but indicated no improved metabolic control following DPP-4 intervention in contrast to other hypoglycaemic agents. Sitagliptin and vildagliptin therapy did not result in weight gain but weight loss was more pronounced following placebo interventions. No definite conclusions could be drawn from published data on sitagliptin and vildagliptin effects on measurements of beta-cell function. Overall, sitagliptin and vildagliptin were well tolerated, no severe hypoglycaemia was reported in patients taking sitagliptin or vildagliptin. All-cause infections increased significantly after sitagliptin treatment but did not reach statistical significance following vildagliptin therapy. All published randomised controlled trials of at least 12 weeks treatment with sitagliptin and vildagliptin only reported routine laboratory safety measurements

Authors' conclusions

DPP-4 inhibitors have some theoretical advantages over existing therapies with oral antidiabetic compounds but should currently be restricted to individual patients. Long-term data especially on cardiovascular outcomes and safety are urgently needed before widespread use of these new agents. More information on the benefit-risk ratio of DPP-4 inhibitor treatment is necessary especially analysing adverse effects on parameters of immune function. Also, long-term data are needed investigating patient-oriented parameters like health-related quality of life, diabetic complications and all-cause mortality.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus

Dipeptidyl peptidase-4 (DPP-4) inhibitors like sitagliptin and vildagliptin are promising new medicines for the treatment of type 2 diabetes mellitus. They are supposed to improve metabolic control (as measured by lowering blood glucose) without causing severe hypoglycaemia (low blood sugar levels leading to unconsciousness and other symptoms).
Altogether 12.864 people took part in 25 studies investigating the new compounds sitagliptin and vildagliptin. Most studies lasted 24 weeks, the longest trials evaluated 52 weeks of treatment. So far, no study reported on patient-oriented parameters like mortality, diabetic complications, costs of treatment and health-related quality of life. When compared to placebo treatment sitagliptin and vildagliptin improved metabolic control. Comparison with other already established blood-glucose lowering drugs did not reveal advantages of DPP-4 treatment. Weight gain was not observed after sitagliptin and vildagliptin therapy. Overall, sitagliptin and vildagliptin were well tolerated, no severe hypoglycaemia was reported in patients taking sitagliptin or vildagliptin. However, all-cause infections increased significantly after sitagliptin treatment but did not reach statistical significance following vildagliptin therapy. Unfortunately, all published randomised controlled trials of at least 12 weeks treatment with sitagliptin and vildagliptin only reported routine laboratory safety measurements. Since the new DPP-4 inhibitors may influence immune function additional long-term data on the safety of these drugs are necessary. Also, cardiovascular outcomes like heart attacks and strokes should not be increased with any antidiabetic therapy but data so far are lacking. Until new information arrives, DPP-4 inhibitors should only be used under controlled conditions and in individual patients.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

Dipeptidyl peptidase4抑制劑 (DPP4 inhibitor)在第2型糖尿病之應用

第2型糖尿病病患之胰島beta細胞的功能會逐漸減退。目前有一類新的藥物出現,是口服DPP4抑制劑,如 sitagliptin 和vildagliptin,對於防止胰島beta細胞的功能衰退有不錯的結果。

目標

評估DPP4抑制劑在治療第2型糖尿病之效果。

搜尋策略

本研究的內容是從MEDLINE, EMBASE和考科藍圖書館經電腦搜尋而來。

選擇標準

這篇研究所選擇的是隨機對照試驗(randomised controlled trials),研究對象是罹患第二型糖尿病的成人,並且至少參與試驗三個月以上。

資料收集與分析

由兩位作者分別評估資料偏差的風險以及摘取數據的風險。並且使用固定效果的統合分析(fixedeffect metaanalysis)來把這些研究的結果綜合在一起。

主要結論

我們找出了二十五篇有品質的研究,其中十一篇研究是使用sitagliptin,另外十四篇則是使用vildagliptin。在sitagliptin這一組,總共有6743個病人,而vildagliptin這組則有6121人。總而來看,實驗的時間短則3個月,長則13個月。在這些研究中,缺少分析死亡率、糖尿病併發症發生率、治療的費用,以及醫療照顧相關的生活品質等相關資料。和對照組相比,使用sitagliptin和vildagliptin分別可以降低糖化血色素約0.7%和0.6%。至於與其他降血糖的藥物之互相比較的研究,數量很少。在這些少數與其他降血糖藥物比較的研究中顯示,使用DPP4抑制劑並沒有明顯對於新陳代謝有較好的控制。和對照組相比,Sitagliptin和vildagliptin不會造成體重的增加,但使用安慰劑組體重下降較明顯。以現有的研究結果來說,sitagliptin以及vildagliptin是否可以減少beta細胞的功能衰退,還缺乏明顯的證據。總括來說,使用sitagliptin和vildagliptin不太會造成不適,也不會有嚴重低血糖的風險。然而,使用sitagliptin之後,會明顯增加整個感染的風險,但vildagliptin這個藥物,是否會增加感染的風險,則沒有達到統計上的意義。另外,這些使用了至少三個月藥物的隨機對照試驗,只提供了常規實驗室檢查的安全性測量。

作者結論

DPP4抑制劑和其他降血糖藥物比較,有一些其他藥物沒有的作用機制上的優勢,只是目前應只被限制於使用在個別的病人身上。而且在廣泛使用這一類的藥物之前,應該有更長期的研究來確定其對於心血管方面之副作用或者是其他安全相關疑慮。特別對於免疫功能方面的副作用,應該有更多的研究來權衡此類藥物之好處以及風險。同時,也需要更多以病人為導向的長期追蹤資料,以評估與健康相關的生活品質改善情形、糖尿病副作用、死亡率等等。

翻譯人

本摘要由臺灣大學附設醫院陳愛華翻譯。

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

總結

DPP4 inhibitor抑制劑在第2型糖尿病之應用: Sitagliptin和vildagliptin等DPP4抑制劑這一類藥物是非常有潛力用來治療第二型糖尿病的新藥。我們期望這類藥物可以改善體內的新陳代謝(例如可以降低血糖),而不會造成像是意識改變等嚴重的低血糖症狀。在本篇的統計的二十五篇研究中,總共有12,864位病患接受sitagliptin或是vildagliptin治療。大部分的研究為期六個月,而其中最長的一篇研究則長達13個月。然而,到目前為止,沒有任何的研究有報告以病人為導向的指標,例如死亡率、糖尿病併發症、治療的花費、與健康相關的生活品質改善。與安慰劑治療的對照組相比,sitagliptin以及vildagliptin可以改善新陳代謝控制。與其他降血糖的藥物相比,DPP4抑制劑沒有明顯的優勢。Sitagliptin以及vildagliptin不會造成體重的上升。總括來說,sitagliptin以及vildagliptin在使用上不會造成太多的不適,也不會造成嚴重的低血糖。然而,感染的風險在sitagliptin這組中有明顯的增加,而在vildagliptin這組中則否。可惜的是,這些隨機試驗研究只提供了常規實驗室檢查的安全性測量。既然這類新藥有可能影響體內的免疫功能,我們就更需要長期的研究來確定此類藥物的安全性。除此之外,也缺乏像是對心血管以及中風這類風險評估方面的研究資料。在這些安全性的考量還不確定之前,DPP4抑制劑只能在良好的追蹤控制下使用,並應只被使用於特定的病人。