Effect of ramipril on the incidence of diabetes
Open accessAbstract
BACKGROUND: Previous studies have suggested that blockade of the renin-angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension. METHODS: In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) and followed them for a median of 3 years. We studied the effects of ramipril on the development of diabetes or death, whichever came first (the primary outcome), and on secondary outcomes, including regression to normoglycemia. RESULTS: The incidence of the primary outcome did not differ significantly between the ramipril group (18.1%) and the placebo group (19.5%; hazard ratio for the ramipril group, 0.91; 95% confidence interval [CI], 0.81 to 1.03; P=0.15). Participants receiving ramipril were more likely to have regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07 to 1.27; P=0.001). At the end of the study, the median fasting plasma glucose level was not significantly lower in the ramipril group (102.7 mg per deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per deciliter [5.74 mmol per liter], P=0.07), though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the ramipril group (135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per liter], P=0.01). CONCLUSIONS: Among persons with impaired fasting glucose levels or impaired glucose tolerance, the use of ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia. (ClinicalTrials.gov number, NCT00095654 [ClinicalTrials.gov].).
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In light of current evidence, the effect of ACE inhibitors and ARBs on diabetes is much smaller than that of antidiabetic drugs, and they are not recommended for the treatment of prediabetes.
“In light of current evidence, the effect of these drugs is much smaller than that of the antidiabetic drugs and they are not recommended for the treatment of prediabetes.”
From Prediabetes: a high-risk state for diabetes development (2012) · cites this paper as [113]
In the DREAM trial, there was no significant association between ramipril and new-onset diabetes.
“Furthermore, in the DREAM trial, there was no significant association between ramipril, another renin-angiotensin-aldosteron system blocker, and new-onset diabetes.113”
From Prediabetes: a high-risk state for diabetes development (2012) · cites this paper as [113]
These findings may be biased because the comparator active treatment groups had different proportions of other antihypertensive treatments known to increase the risk of diabetes, such as β-blockers and thiazide diuretics.
“However, these findings may be biased as the comparator active treatment groups had different proportions of other antihypertensive treatments that are known to increase the risk of diabetes (β-blockers, thiazide diuretics).112,113”
From Prediabetes: a high-risk state for diabetes development (2012) · cites this paper as [113]
In the DREAM study, median two-hour glucose following OGTT was lower in the ramipril group.
“The median two-hour glucose following OGTT was also lower in the ramipril group.”
From The Vasculature in Prediabetes (2018) · cites this paper as [227]
In the DREAM study, ramipril did not reduce incident diabetes in patients with IFG.
“In the DREAM study, ramipril did not reduce incident diabetes in patients with IFG.227”
From The Vasculature in Prediabetes (2018) · cites this paper as [227]
In the DREAM study, a greater proportion of patients treated with ramipril regressed to fasting normoglycemia compared to placebo (42.5% versus 38.2%, p<0.001).
“A greater proportion of patients treated with ramipril regressed to fasting normoglycemia compared to placebo treated patients (42.5% versus 38.2%, p<0.001), however.”
From The Vasculature in Prediabetes (2018) · cites this paper as [227]
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- Authors
- The DREAM Trial Investigators
- Corresponding author
- The DREAM Trial Investigators
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2006-10-12
- Volume
- 355
- Issue
- 15
- Pages
- 1551-1562
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2161392015
- Cited by
- 737
- References
- 25
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 15 · 2023: 14 · 2022: 13 · 2021: 15 · 2020: 15 · 2019: 22 · 2018: 28 · 2017: 27 · 2016: 14 · 2015: 30 · 2014: 36 · 2013: 31 · 2012: 48
- FWCI
- 68.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Omeka S (Universidad de La Frontera) (submittedVersion, cc-by-nc-nd)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- ramipril, diabetes incidence, renin-angiotensin system blockade, impaired fasting glucose, impaired glucose tolerance, rosiglitazone, ACE inhibitors, cardiovascular disease prevention, hypertension, fasting blood glucose, oral glucose tolerance
- MeSH terms
- Adult, Aged, Angiotensin-Converting Enzyme Inhibitors, Blood Glucose, Diabetes Mellitus, Double-Blind Method, Fasting, Female, Humans, Male, Middle Aged, Incidence, Ramipril, Glucose Intolerance
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