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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Renin-angiotensin system inhibition prevents type 2 diabetes mellitus - part 1: a meta-analysis of randomised clinical trials

AJ Scheen.

Review published: 2004.

CRD summary

This review assessed the effects of renin-angiotensin system (RAS) inhibition on the development of type 2 diabetes in patients with arterial hypertension or congestive heart failure. The author concluded that RAS inhibition may help prevent type 2 diabetes. Given the lack of a quality assessment and the insufficient reporting of the review methods, the reliability of the author's conclusions cannot be adequately assessed.

Authors' objectives

To assess the effects of renin-angiotensin system (RAS) inhibition on the incidence of new cases of type 2 diabetes mellitus (T2DM) in patients with arterial hypertension or congestive heart failure (CHF).

Searching

MEDLINE, EMBASE and the Science Citation Index were searched from January 1990 to June 2004 for publications in the English language; no search terms were reported. The reference lists of identified studies were also manually checked.

Study selection

Study designs of evaluations included in the review

Only randomised controlled trials (RCTs) were eligible for inclusion in the review.

Specific interventions included in the review

Studies that assessed the effects of either an angiotensin-converting enzyme inhibitor or a selective angiotensin receptor AT1 blocker, compared with a placebo or other active drug, were eligible for inclusion. The specific interventions in the eligible studies were enalapril, lisinopril, captopril, ramipril, losartan, candesartan and valsartan, all at a variety of dosages. Active comparator drugs were beta-blockers or diuretics, or amlodipine. The mean follow-up ranged from 1 to 6 years.

Participants included in the review

Studies involving data on non-diabetic participants with arterial hypertension or CHF were eligible for inclusion. In the included studies, the mean age of the participants ranged from 52.4 to 76.1 years, the mean body mass index (where reported) ranged from 26.7 to 29.8, and the percentage of participants with diabetes at baseline ranged from 4.8 to 38.9%.

Outcomes assessed in the review

Studies that assessed the incidence of new cases of T2DM and presented the criteria used to define the confirmation of diabetes were eligible for inclusion in the review.

How were decisions on the relevance of primary studies made?

The author did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

The author did not state that they assessed validity.

Data extraction

The author did not state how the data were extracted for the review, or how many reviewers performed the data extraction. The author stated that details of participant characteristics and study design were carefully recorded.

Methods of synthesis

How were the studies combined?

The pooled odds ratios with 95% confidence intervals (CIs) for new T2DM cases were calculated using the Mantel-Haenszel fixed-effect model; however, the results were reported as relative risks. The number-needed-to-treat to prevent one case of T2DM was also calculated.

How were differences between studies investigated?

The chi-squared test was used to investigate statistical heterogeneity. Subgroup analyses were performed: angiotensin-converting enzyme inhibitor versus selective angiotensin receptor AT1 blockers; arterial hypertension versus CHF; and placebo versus active control.

Results of the review

Ten RCTs (n=76,069) were eligible for inclusion in the review.

The overall effect of RAS inhibition was a mean relative risk reduction of T2DM of 22% (95% CI: 18, 26, P<0.00001). However, significant statistical heterogeneity was identified (P=0.004).

The number-needed-to-treat was 45 over 4 to 5 years.

A similar beneficial effect of RAS inhibition on the incidence of T2DM was observed in all of the subgroup analyses.

Authors' conclusions

Drugs that inhibit RAS activity may be considered as a valuable approach to prevent T2DM.

CRD commentary

The review question was clear in terms of the intervention, participants, outcomes and study designs of interest. A limited search was performed and no search terms were reported, which increases the possibility of the omission of relevant studies, and language and publication bias. No details of the methods employed to select studies and extract the data were reported, so it was not possible to ascertain whether the potential for reviewer bias or errors was reduced. The validity of the included studies was not assessed, which means that it is unclear whether the conclusions are based on high-quality studies or not.

Adequate details of the included studies were provided and, although significant heterogeneity was identified, the directions of treatment effects were generally consistent. The results of the subgroup analyses were all similar but, since no details of heterogeneity within subgroups were reported, it is unclear how reliable these results are. Given the lack of a validity assessment and insufficient reporting of the review methods, the reliability of the author's conclusions cannot be fully assessed. In addition, the limited search means that there is a possibility that some relevant studies were not identified.

Implications of the review for practice and research

Practice: The author stated that drugs that inhibit RAS activity may be considered as a valuable approach to prevent T2DM.

Research: The author stated that, depending on the results of an ongoing RCT, it may be interesting to consider targeting further research in populations that are at higher risk of developing T2DM (such as obese patients with impaired glucose tolerance).

Bibliographic details

Scheen A J. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus - part 1: a meta-analysis of randomised clinical trials. Diabetes and Metabolism 2004; 30(6): 487-496. [PubMed: 15671918]

PubMedID

15671918

Indexing Status

Subject indexing assigned by NLM

MeSH

Angiotensin-Converting Enzyme Inhibitors /therapeutic use; Captopril /therapeutic use; Diabetes Mellitus, Type 2 /prevention & control; Humans; Hypertension /prevention & control; Randomized Controlled Trials as Topic; Receptor, Angiotensin, Type 1 /drug effects; Renin-Angiotensin System /drug effects

AccessionNumber

12005009441

Date bibliographic record published

30/06/2006

Date abstract record published

30/06/2006

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 15671918

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