Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis

Nazarzadeh, M., Bidel, Z., Canoy, D., Copland, E., Wamil, M., Majert, J., … & Trialists’Collaboration, B. P. L. T. | 2021 | Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis | The Lancet398 | 10313 | P. 1803-1810.

This meta-analysis used large-scale individual participant data from randomised controlled trials to investigate the effect of blood pressure lowering and the differential effects of five major classes of antihypertensives on risk of new-onset type 2 diabetes. A fixed level of 5 mm Hg reduction in systolic blood pressure reduced the risk of diabetes by 11 per cent. This treatment effect constituted quantitatively and qualitatively diverging effects of major antihypertensive drug classes. In analysis of specific drug classes versus placebo, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers had the strongest protective effect on the risk of diabetes. For calcium channel blockers no material effect was found, while β blockers and thiazide diuretics increased the risk.

The experts behind this study suggest that their findings indicate that blood pressure lowering can help prevent diabetes in addition to its well established beneficial effects in reducing cardiovascular events. The relative magnitude of reduction per 5 mm Hg systolic blood pressure lowering was similar to those reported for prevention of major cardiovascular events, which will strengthen the case for blood pressure reduction through lifestyle interventions known to reduce blood pressure, and blood pressure lowering treatments with drugs, and possibly device therapies (Source: Nazarzadeh et al, 2021).

Summary

Background

Blood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials.

Methods

We performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists’ Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of follow-up in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons.

Findings

145 939 participants (88 500 [60·6%] men and 57 429 [39·4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4·5 years (IQR 2·0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0·89 [95% CI 0·84–0·95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0·84 [95% 0·76–0·93]) and angiotensin II receptor blockers (RR 0·84 [0·76–0·92]) reduced the risk of new-onset type 2 diabetes; however, the use of β blockers (RR 1·48 [1·27–1·72]) and thiazide diuretics (RR 1·20 [1·07–1·35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1·02 [0·92–1·13]).

Interpretation

Blood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual’s clinical risk of diabetes.

Funding

British Heart Foundation, National Institute for Health Research, and Oxford Martin School.

The Lancet Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis [paper]

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