BP Lowering and Risk of New-Onset Type 2 Diabetes

The Lancet:

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It is well-established that blood pressure control is an important strategy in reducing cardiovascular events among people with diabetes.

This data analysis that included studies comprised of over 145,000 participants finds that a reduction of 5 mm Hg in systolic blood pressure was associated with an 11% reduced risk of developing type 2 diabetes.

Among the major classes of anti-hypertensive medications, ACE inhibitors and ARBs were associated with a reduced risk of developing diabetes, calcium channel blockers did not have a statistically significant impact, but beta blockers and thiazide diuretics increased the risk for developing diabetes. No material effect was found for Calcium Channel Blockers.

This study has important implications for strategies to prevent diabetes in the primary care setting, as well as treatments we choose to manage hypertension.

Antihypertensive Medications Prevent Diabetes

Diabetes dramatically increases a person’s cardiovascular risk. So prevention of diabetes would be most beneficial for patients and the health care system. In the Diabetes Prevention Program (DPP), lifestyle and metformin were shown to prevent the onset of diabetes. Some studies showed that a 20 mm Hg increase in the systolic blood pressure was associated with a 77% increased risk of type 2 diabetes.

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· Can lowering blood pressure reduce the risk of developing type 2 diabetes in the first place?

· Does the medication we prescribe to achieve this goal make a difference?

First of all, study found that blood pressure reduction is good regardless of which agent was used. For a 5 mm Hg reduction in systolic blood pressure, there was an 11% reduction in Type 2 diabetes risk which was significant.

Now as for which anti-hypertensive drug was the best – here are the results compared to placebo:

· Βeta blockers – 48% increased risk of diabetes

· Thiazide diuretics - 20% increased risk of diabetes

· Calcium channel blockers (CCB) – Neutral

· Angiotensin-converting enzyme (ACE) inhibitors – 16% reduced risk of diabetes

· Angiotensin II receptor blockers (ARB) – 16% reduced risk of diabetes

This shows a clear benefit for ACE inhibitors and ARBs.

Therefore, expert advised, clinicians should use ACE inhibitors or ARBs not just in patients with diabetes but in patients without diabetes as well because they could help prevent some of them from developing diabetes.

Now combining ACE inhibitors and ARBs is not recommended for hypertension treatment so it would make the most sense to combine with a calcium channel blocker (CCB). This combination of ACE inhibitor and CCB was shown in the Accomplish study, to be superior to ACE inhibitor-diuretic combination.

So perhaps clinicians should rethink which agent to start for their hypertensive patient and also which agents to combine.

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Abstract

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. Authors aimed to examine this question using individual participant data from major randomised controlled trials.

METHODS

Authors 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). Authors 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 authors 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, 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%. Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers reduced the risk of new-onset type 2 diabetes; however, the use of β blockers and thiazide diuretics increased this risk, and no material effect was found for calcium channel blockers.

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.

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