Preventing Diabetes with Antihypertensives

Research on the use of antihypertensives showed that elevated blood pressure is a modifiable risk factor for new-onset type 2 diabetes.

Today, around 9% of the adult population worldwide is affected by diabetes. In a recent study, researchers from the University of Bristol suggested that lowering blood pressure is an effective strategy for preventing type 2 diabetes. They also reported that specific medications that lower blood pressure reduces the onset risk of diabetes. Although the role is unclear, lowering blood pressure is an established strategy for preventing macrovascular and microvascular complications associated with diabetes. In an attempt to study the role of antihypertensives in diabetes prevention, Kazem Rahimi, FRCP, and his colleagues conducted a study using data from randomized controlled trials.

The researchers conducted a one-stage individual participant data meta-analysis pooled to investigate the effect of lowering blood pressure on the risk of new-onset type 2 diabetes. The differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes were compiled into an individual participant data network meta-analysis. They 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 agents that had at least 1000 persons-years of follow-up in each randomly allocated arm. Patients with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded from the study. They used the stratified Cox proportional hazards model for the one-stage individual participant data meta-analysis, and logistic regression models for the individual participant data network meta-analysis, to calculate the relative risk (RR) for drug class comparisons.

There were 19 randomized controlled trials (RCTs) with 145,939 participants (60.6% men and 39.4% women) in the one-stage individual participant data meta-analysis and 22 trials in the individual participant data network meta-analysis. A total of 9,883 participants were diagnosed with new-onset type 2 diabetes after a median follow-up of 4 to 5 years. The incidence rate for developing a new-onset type 2 diabetes event per 1000 person-years was 15.94 (95% CI 15.47- 16.42) in the intervention group and 16.44 (95% CI 16.01- 16.87) in the comparator group. After investigating the effects of the five major antihypertensive drug classes, the data showed that in comparison to the placebo, angiotensin-converting enzyme (ACE) inhibitors (RR 0.84 [95% CI 0.76- 0.93]) and angiotensin II receptor blockers (ARBs) (RR 0.84 [95% CI 0.76- 0.92]) reduced the risk of new-onset type 2 diabetes. However, the use of beta-blockers (RR 1.48 [95% CI 1.27- 1.72]) and thiazide diuretics (RR 1.20 [95% CI 1.07- 1.35]) increased the risk of new-onset type 2 diabetes. No material effect was found for calcium channel blockers (CCBs) (RR 1.02 [95% CI 0.92- 1.13]).

Through this large-scale analysis of individual participant data from the RCTs, the researchers found evidence for the preventative effects of blood pressure lowering on the risk of type 2 diabetes, with an 11% reduction in the risk of new-onset type 2 diabetes per 5 mm Hg reduction in systolic blood pressure. With consistent results from both RCTs and genetic analyses, the researchers showed that elevated blood pressure is indeed a modifiable risk factor for new-onset type 2 diabetes in people without a diagnosis of diabetes, with a relative effect size like those seen for the prevention of significant cardiovascular disease. This evidence that blood pressure reduction and diabetes are linked presents the entire health field with an opportunity to modify disease risk. By prescribing antihypertensive medications to supplement healthy lifestyle choices through diet and exercise, modification can be achieved.

Using randomized evidence from significant pharmacological blood pressure-lowering trial data, this study showed consistent evidence suggesting that the preventative effects of blood pressure reduction on type 2 diabetes risk are causal. Therefore, reducing blood pressure is likely to prevent new-onset type 2 diabetes. The evidence also supports the indication for ACE Inhibitors and ARBs specifically for the prevention of type 2 diabetes, which may further refine the selection of drug choice according to individual patient risk profiles.

Practice Pearls:

• 9% of the adult population is affected by diabetes.
• Research suggests that antihypertensive medications can help prevent new-onset type 2 diabetes.
• ACE Inhibitors and ARBs should be considered the most favorable options when the clinical risk of diabetes is a concern.

Reference for “Preventing Diabetes with Antihypertensives”:
Nazarzadeh, M, et al. Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis. The Lancet. November 19, 2021,

Kevin Suarez, PharmD. Candidate, Creighton University, School of Pharmacy and Health Professions