Reducing the risk of macrovascular events, including myocardial infarction and stroke, is a major goal when treating diabetes. Despite this focus, of the major randomized trials used to support current diabetes guidelines (ACCORD, ADVANCE, UKPDS 33, UKPDS 34, VADT), none showed reductions in macrovascular events when the trial results were first reported.1,2 For example, UKPDS is still frequently cited in support of aggressive glucose lowering, yet when the primary outcome data were presented in 1998, the results showed no difference between groups in terms of reducing the risk of all-cause mortality (relative risk [RR], 0.94 [95% CI, 0.80-1.10]), myocardial infarction (RR, 0.84 [95% CI, 0.71-1.00]), heart failure (RR, 0.91 [95% CI, 0.54-1.52]), stroke (RR, 1.07 [95% CI, 0.68-1.69]), or kidney failure (RR, 0.73 [95% CI, 0.25-2.20]). Only 1 of 21 clinical end points showed a statistically significant difference attributable to intensive glucose control after 10 years of treatment.3 Of the 21 end points, only the need for retinal photocoagulation was significantly reduced with intensive glucose lowering, although the effect size was small (RR, 0.71 [95% CI, 0.53-0.98]). An effect of aggressive glucose lowering was only seen 10 years after the trial was completed, when patients were no longer receiving the assigned interventions and had similar glycated hemoglobin levels.4 This observational analysis of this randomized clinical trial eventually showed reduction in macrovascular disease, including for myocardial infarction (RR, 0.85 [95% CI, 0.74-0.97]) and all-cause mortality (RR, 0.80 [95% CI, 0.79-0.96]) but not for stroke (RR, 0.91 [95% CI, 0.73-1.13]).
Livingston EH. The Role of Bariatric Surgery in Managing the Macrovascular Complications of Obesity-Related Type 2 Diabetes. JAMA. 2019;322(13):1259–1260. doi:10.1001/jama.2019.14577
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