medwireNews: Statin therapy is associated with a moderate, dose-dependent increase in diabetes diagnoses due to small increases in glycemia, particularly among people already at high risk for diabetes, meta-analysis data show.
However, “[t]he diabetes-related risks arising from the small changes in glycaemia resulting from statin therapy are greatly outweighed by the benefits of statins on major vascular events when the direct clinical consequences of these outcomes are taken into consideration,” write members of the Cholesterol Treatment Trialists’ (CTT) Collaboration (University of Oxford, UK) in The Lancet Diabetes & Endocrinology.
They analyzed individual data for more than 154,000 participants of 23 randomized, controlled trials that compared statin therapy of at least 2 years’ scheduled duration with placebo or compared more intensive statin therapy with less intensive therapy. Around one in five participants had diabetes at baseline.
The researchers report that data from 14 trials showed that low- or moderate-intensity statin regimens resulted in a 10% relative increase in new-onset diabetes versus placebo, with new diagnoses occurring at annual rates of 1.2% and 1.3%, respectively.
Two trials compared high-intensity statin use with placebo. In these studies, the annual rate of new diabetes diagnoses was 4.8% among individuals allocated to a high-intensity statin regimen and 3.5% among those given placebo, which corresponded to a 36% relative increase in new diabetes diagnoses with the high-intensity regimen.
Furthermore, most (62%) cases of new-onset diabetes occurred among participants who were already in the top quartile of glycemia at baseline, regardless of statin intensity.
This finding “make[s] clear that the majority of new diagnoses of diabetes resulting from statin therapy will occur among people who are already close to the biochemical diagnostic threshold for diabetes,” the authors write.
The investigators point out that the incidence of new-onset diabetes was substantially higher in both the intervention and placebo groups in the two high-intensity trials than it was in the low- or moderate-intensity statin trials. They say that this was due to more participants in the high-intensity statin trials having at least one follow-up glycated hemoglobin (HbA1c) measurement.
“In practice, such measurements might not be obtained routinely in people without diabetes, but it is likely that the rate of diagnosis of diabetes would be higher than it currently is if such a practice was widely adopted,” they say.
The researchers also report that, in seven trials, glucose concentrations were measured during follow-up. These measurements showed that, among participants without baseline diabetes, mean glucose concentration increased by 0.04 mmol/L during treatment with both low- or moderate-intensity and high-intensity statins. Mean HbA1c, measured during follow-up in two trials, increased by 0.06% with low- or moderate-intensity statins and 0.08% with high-intensity statins.
Among the participants who already had diabetes at baseline, low- or moderate-intensity statin therapy was associated with a 10% relative increase in worsening glycemia versus placebo, while high-intensity statin therapy was associated with a 24% relative increase.
The CTT Collaborators conclude that their meta-analysis “advances our understanding of the adverse effects of statin therapy on diabetes” and say the data “should further inform clinical guidelines regarding clinical management of people taking statin therapy.”
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Lancet Diabetes Endocrinol 2024; doi:10.1016/ S2213-8587(24)00040-8