Alpha-glucosidase inhibitors for people with impaired glucose tolerance or impaired fasting blood glucose

 

Abstract

Background

Alpha-glucosidase inhibitors (AGIs) reduce blood glucose levels and may thus prevent type 2 diabetes and cardiovascular disease in patients with impaired glucose tolerance (IGT). These possible effects, and the effects on quality of life, plasma lipids and body weight, have never been investigated in a systematic literature review and meta-analysis.

Objectives

To assess the effects of alpha-glucosidase inhibitors in patients IGT or impaired fasting blood glucose (IFBG), or both.

Search methods

We searched The Cochrane Library, PUBMED, EMBASE, Web of Science, LILACS, databases of ongoing trials, reference lists of relevant reviews, and we contacted experts and manufacturers.

Selection criteria

Randomised controlled trials of at least one-year duration in patients with IGT or IFBG, or both, comparing AGI monotherapy with any other intervention.

Data collection and analysis

Two reviewers read all abstracts, assessed quality and extracted data independently. Discrepancies were resolved by consensus or by the judgement of a third reviewer.

Main results

We included five trials (2360 participants), all investigating acarbose, that included patients with IGT or patients 'at increased risk for diabetes' (n = 1). Study duration was one, three (n = 2), five and six years. One study was at low risk of bias and four studies at high risk of bias. Except for the outcome incidence of type 2 diabetes in acarbose versus no treatment (two studies), meta-analyses were not possible. Data from the study at low risk of bias suggests that acarbose decreases the occurrence of type 2 diabetes (NNT = 10), cardiovascular events (NNT = 50, based on 47 events, study not initially powered for this outcome), post-load blood glucose (-0.6 mmol/L, 95% CI -1.0 to -0.3) and body mass index (0.3 kg/m², 95% CI -0.1 to -0.5). No statistically significant effects were observed on mortality, other morbidity, glycated haemoglobin, fasting blood glucose, lipids and blood pressure. The effects on the incidence of type 2 diabetes were confirmed in two studies at high risk of bias (OR 0.2, 95% CI 0.1 to 0.6). Adverse effects were mostly of gastro-intestinal origin (OR 3.5, 95% CI 2.7 to 4.4).

Authors' conclusions

There is evidence that acarbose reduces the incidence of type 2 diabetes in patients with IGT. However, it is unclear whether this should be seen as prevention, delay or masking of diabetes. Acarbose may prevent the occurrence of cardiovascular events, but this finding needs to be confirmed in more studies.

 

Plain language summary

Alpha-glucosidase inhibitors for people with impaired glucose tolerance or impaired fasting blood glucose

Alpha-glucosidase inhibitors (acarbose, miglitol, voglibose) are drugs that delay the breakdown of carbohydrates in the gut, and consequently slow down the absorption of sugars. Patients with type 2 diabetes may use it therapeutically. People with a raised blood glucose level (without being a diabetes patient) may use this drug in order to prevent developing type 2 diabetes and diabetes related morbidity such as cardiovascular diseases. To find evidence for these assumptions, we searched the medical literature for randomised controlled trials of at least one-year duration, investigating alpha-glucosidase inhibitors for patients with impaired glucose tolerance (IGT) or impaired fasting blood glucose (IFBG). Patients with IGT or IFBG have raised blood glucose levels, but do not meet the criteria for having type 1 or type 2 diabetes.
In our review we included five studies, representing 2360 participants, investigating acarbose. Of these studies, one was of high quality, and two did not show exact data, as the results were not available in full publication. The study of high quality yielded that if 10 people with IGT would take acarbose for three years, one case of diabetes would not occur. This finding was confirmed in studies of lower quality. The relevance of this finding is questionable because we found only small effects on blood glucose levels, and the mechanism behind this finding remains unclear: does acarbose really prevent diabetes does it delay the occurrence or mask type 2 diabetes? With respect to the effect on the occurrence of cardiovascular diseases, a dubious preventive effect of acarbose on the occurrence of myocardial infarctions was found. However, definitive conclusion could not be drawn and this latter finding should be confirmed in other studies. We found no statistically significant effects on the occurrence of death, other complications related to IGT, or quality of life. Side effects were mostly of gastro-intestinal origin (flatulence, diarrhoea).
The low number of studies, the poor quality of four of the included studies, and the missing data of two included studies limited this review. First, the missing data of two included studies need to be made available for a future update of this review. Next, the results of the two ongoing studies should be implemented in the review. If, after that, the evidence remains inconclusive, new trials should be initiated in order to investigate the true value of alpha-glucosidase inhibitors for patients with impaired glucose tolerance or impaired fasting blood glucose.

 

摘要

背景

治療葡萄糖失耐症或空腹血糖障礙之患者的Alphaglucosidase抑制劑

Alphaglucosidase抑制劑(AGIs)可降低血糖，且可能因此而預防有葡萄糖耐量障礙的病患發生第2型糖尿病和心血管疾病。這些可能的作用，及對生活品質，血脂和體重的影響，從未用系統性文獻回顧和統合分析進行調查。

目標

評估Alphaglucosidase抑制劑在治療葡萄糖失耐症(IGT) 或空腹血糖障礙(IFBG) 或兩者間兼有之患者的作用。

搜尋策略

我們檢索The Cochrane Library(臨床試驗數據庫，前身名為CENTRAL)，PUBMED，EMBASE，Web of Science，LILACS，正在進行的試驗的資料庫，及相關回顧之參考文獻目錄。我們也與相關的專家和藥廠接觸。最後一次檢索的日期是2006年2月。

選擇標準

收錄有對至少罹患葡萄糖失耐症(IGT) 或空腹血糖障礙(IFBG) 或兩者間兼有達1年之患者進行Alphaglucosidase抑制劑單一療法與其他任何介入作比較的隨機對照試驗。

資料收集與分析

兩名回顧者獨立地閱讀所有的摘要，評估文獻的品質和摘錄的資料。如有歧見，則以第三位回顧者的評判或以共識的方式解決。

主要結論

我們收錄了5篇試驗(共有2360受試者)，都是調查acarbose，受試者都有糖失耐症或是“得糖尿病之風險增加”的患者(有1篇試驗)。研究期間為1年，3年(有2篇試驗)，5和6年。有1篇研究是低偏差風險，其他4篇研究則是高偏差風險。除了可調查比較使用acarbose與不治療(有2篇研究)發生第2型糖尿病的發生率結果外，要做統合分析是不可能的。從具低偏差風險的研究所得到的資料，指出acarbose可降低第2型糖尿病的發生(NNT = 10)，降低心血管事件(NNT = 50，在47個事件的基礎上，研究初期未對此結果做檢力檢定)，降低後負荷血糖(−0.6 mmol / L，95％CI −1.0到−0.3)和身體質量指數(0.3 kg/m2，95％CI −0.1到−0.5)。在死亡率，其他發病率，糖化血色素，空腹血糖，血脂和血壓方面，無統計上顯著的作用被觀察到。對第2型糖尿病發生率的作用，在2篇具高偏差風險的研究中得到證實(OR 0.2，95％CI 0.1到0.6)。不良作用主要是來自胃腸道(OR 3.5，95％CI 2.7到4.4)。

作者結論

有證據顯示acarbose可降低糖失耐症患者的第2型糖尿病發生率。不過，目前還不清楚是否這樣的發現應被視為是預防，延緩或不彰顯糖尿病。acarbose可能可以預防心血管事件的發生，但這樣的發現還需要更多的研究來證實。

翻譯人

本摘要由慈濟醫院李哲全翻譯。

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

總結

治療糖失耐症或空腹血糖障礙之患者的Alphaglucosidase抑制劑Alphaglucosidase抑制劑(acarbose, miglitol, voglibose)是一種延緩碳水化合物在腸道中裂解的藥物，因此減慢糖的吸收。在治療方法上，第2型糖尿病患可使用它。血糖升高的人(尚非為糖尿病患者)可使用這種藥物，以防止第2型糖尿病和與糖尿病有關的疾病，如心血管疾病。為了找到這些假設的證據，我們搜查了調查至少用Alphaglucosidase抑制劑治療葡萄糖失耐症(IGT)或空腹血糖障礙(IFBG)病患達1年以上的隨機對照試驗的醫學文獻。葡萄糖失耐症或空腹血糖障礙的病患有高血糖情形，但尚不符合有第1型或第2型糖尿病的標準。在我們的回顧中，我們收錄了5篇調查acarbose的研究，共有2360受試者。這些研究中，有1篇的方法學品質高，而有2篇因在發表的報告中沒有結果可獲得，所以沒有呈現出摘錄的資料。這個高方法學品質的研究顯示，只要10位糖失耐症的人使用acarbose 3年，可使1人不會發生糖尿病。這一發現也在1篇方法學品質較低的研究中得到證實。這個發現的相關性是有問題的，因為我們發現acarbose對血糖只有小部分的影響，且這一發現背後的機制仍不清楚：acarbose是否真的可預防糖尿病?是否延緩第2型糖尿病的發生或不彰顯第2型糖尿病？關於對心血管疾病發生的作用，一個不確定的acarbose對心肌梗塞之發生的預防作用被發現。然而，最終的結論無法獲得，且後者的發現應在其他的研究中被確認。我們發現在死亡的發生，其他與葡萄糖失耐症相關的併發症，或生活品質上，無統計上顯著的影響。副作用主要是來自胃腸道(腹脹，腹瀉)。收錄的研究數目低，納入了4篇低方法學品質研究，和納入了的2篇缺失數據的研究限制了本回顧。首先，2篇缺失數據的研究必須在本回顧未來更新時被獲得。其次，這2篇正在進行的研究的結果應在回顧中被貫徹執行。如果在這之後，證據仍未有定論，新的試驗應該開始，以調查Alphaglucosidase抑制劑對葡萄糖失耐症或空腹血糖障礙病患的真正價值。