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Lowering blood pressure does not decrease the risk of T2DM in persons with hypertension; ACEIs/ARBs do
Clinical Question
Does blood pressure lowering prevent the development of type 2 diabetes mellitus in adults with hypertension?
Bottom line
In this study, the crude incidence of T2DM was not associated with lower blood pressure. However, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were associated with a decreased risk of developing T2DM, and beta-blockers and thiazides were associated with an increased risk. 1a
Reference
Study design: Meta-analysis (randomized controlled trials)
Funding: Government
Setting: Various (meta-analysis)
Synopsis
This team pooled individual patient data taken from 22 randomized trials that evaluated various antihypertensive drugs. The included studies had at least 1000 person-years of follow-up in each intervention arm and reported on the development of type 2 diabetes mellitus (T2DM). These authors don’t report the methodologic quality of the included studies. Some of the included studies had a placebo arm; others used head-to-head comparisons of drugs (in the latter situation, the arm with the greater reduction in systolic blood pressure was considered the intervention). After excluding those persons who were known to have diabetes, the authors had 145,939 participants with a median of 4.5 years of follow-up. A total of 9883 (6.8%) participants developed T2DM. The crude rate of incident T2DM in the intervention group was not statistically different than in the comparator group (15.94 and 16.44 per 1000 person-years, respectively, with overlapping confidence intervals). After performing some fancy statistical gymnastics, the authors report that a reduction of systolic blood pressure by 5 mm Hg was associated with an 11% reduced risk of developing diabetes (hazard ratio 0.89; 95% CI 0.84 - 0.95). Although the included studies used various means to determine the presence of diabetes, the authors conducted sensitivity analyses and found no evidence for differential outcomes. The authors also used data from the 22 trials to conduct a network meta-analysis and found that, relative to placebo, there was a lower risk of T2DM with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (relative risk [RR] 0.84; 0.76 - 0.93 and RR 0.85; 0.76 - 0.92, respectively); there was no association with calcium channel blockers; and there was an increased risk with beta-blockers (RR 1.48; 1.27 - 1.72) and thiazides (RR 1.20; 1.07 - 1.35). The authors fail to report harms associated with treatment.
Reviewer
Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI
Comments
the challenge of controls
This feels very dodgy - did the studies include patients who were treated with diet and life style changes alone? And how can they possibly have controlled for the use of diet and life style changes.
Other options
Would like differentiation between different diuretic, HCTZ, vs indapamide and chlorthalidone. Better outcomes reported
Didn't expect beta-blockers to be an issue; although known to be an issue>65.
Until I know better, will use indapamide or chorthalidone only when extra control needed, and beta blockers when another reason to use-eg tachyarrhythmias, migraine, essential tremor, cad.
Hypertension treatment and risk of T2DM
Hmm, the reviewers notes "fancy statistical gymnastics", which in top of a network meta-analysis to do other parts of their paper and a note that "various" ways were used to diagnosis T2DM. Somehow it makes me leery of whatever findings and conclusions the authors come up with. Not ready to buy into this paper.
ace/arbs ve beta blockers/thiazides
ace/arbs reduce type 2 dm but betablockers/thiazides may increase incidence
ARB and DM development
Having been involved in some of the early ARB trials (ontarget/trascend) it became evident that this was the case. This is not something that is new to me