Statins linked to moderate increase in diabetes risk, but overall benefits bear more weight

Statin therapy appears to result in a modest elevation in blood sugar levels, increasing the likelihood of diabetes development especially among people whose blood sugar levels are already near the diagnostic threshold, according to a meta-analysis.

Pooled individual participant data from 19 randomized controlled trials that participated in the Cholesterol Treatment Trialists’ (CTT) Collaboration showed that the rate of new-onset diabetes relative to placebo was 10-percent higher with low-to-moderate–intensity statin (1.3 percent vs 1.2 percent per year; rate ratio [RR], 1.10, 95 percent confidence interval [CI], 1.04–1.16) and 36-percent higher with high-intensity statin (4.8 percent vs 3.5 percent per year; RR, 1.36, 95 percent CI, 1.25–1.48). [Lancet Diabetes Endocrinol 2024;doi:10.1016/S2213-8587(24)00040-8]

Participants without diabetes at baseline who took statins saw slight increases in their mean glucose levels (around 0.04 mmol/L across all dosing intensities) and mean HbA_1c (0.06 percent with low-to-moderate–intensity and 0.08 percent with high-intensity dosing).

Notably, roughly 62 percent of the participants who developed diabetes during the study and had a baseline measure of glycaemia already had very high blood sugar levels even before starting statin therapy.

Among participants with baseline diabetes, on the other hand, the rate of worsening glycaemia relative to placebo was 10-percent higher with low-to-moderate–intensity statin (16.3 percent vs 15.4 percent per year; RR, 1.10, 95 percent CI, 1.06–1.14) and 24-percent with high-intensity statin (16.0 percent vs 12.8 percent per year; RR, 1.24, 95 percent CI, 1.06–1.44).

“The RRs for new-onset diabetes did not vary significantly over time. We hypothesize that the reason for this finding is that, in each successive year of follow-up, a new group of people becomes at risk of exceeding the diagnostic threshold for diabetes because of an age-related increase in glycaemia, and those taking a statin will be slightly more likely to do so,” the investigators pointed out.

“By contrast, among people with a known diagnosis of diabetes at baseline, the early excess of worsening glycaemia with a statin did not persist in the long term, perhaps because glycaemic control is typically monitored in such individuals and likely to be managed,” they added.

Beyond blood sugar

The investigators emphasized that statins remain greatly beneficial, even with a slight diabetes risk increase.

“Our analyses strongly suggest that the absolute benefits of statin therapy greatly outweigh any excess risks of diabetes associated with the small increase in glycaemia they induce. Any theoretical adverse effects of statins on cardiovascular risk that might arise from these small increases in glycaemia (or, indeed, from any other mechanism) are already accounted for in the overall reduction in cardiovascular risk that is seen with statin therapy in [the trials included in the meta-analysis],” they pointed out.

Likewise, in the JUPITER trial, the cardioprotective effects of rosuvastatin have been shown to be much stronger than the potential downside of the risks of new-onset diabetes, even for participants without hyperlipidaemia but with high C-reactive protein levels. [Lancet 2012;380:565-571]

The takeaway is 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 investigators stated.

“[Additionally,] since the effect of statin therapy on measures of glycaemia within an individual is small, there is likely to be little clinical benefit in measuring glucose concentrations and HbA1c values routinely after starting statin therapy with the aim of making comparisons to values taken before the initiation of a statin,” they continued.

Nevertheless, the investigators acknowledged that regular diabetes screening and blood sugar management are still essential, in accordance with current clinical guidelines. They believed that their study can further inform clinical guidelines regarding clinical management of people taking statin therapy.