Statins Slightly Up Diabetes Risk But Cardiovascular Benefits Remain, Finds Study

In a recent study published in The Lancet Diabetes & Endocrinology, researchers performed a meta-analysis of long-term, large-scale, randomized, double-blinded controlled trials to determine the influence of statin medication on worsening glycemia and diabetes diagnosis.

Atherosclerotic cardiovascular disease is a serious worldwide health problem, with diabetes playing a significant role. Statins, which have limited side effects, can raise diabetes incidence compared to placebo or standard treatment. However, due to the scarcity of evidence for these meta-analyses, evaluating the impact of statin medication on the likelihood of acquiring new diabetes is inadequate. There is limited understanding of individuals at high risk in cases of additional risk occurring after commencing medication and ways in which statin therapy affects glycemic control in those with established diabetes.

Study: Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis. Image Credit: Roger Ashford / Shutterstock

About the study

In the present meta-analysis, researchers explored the effects of statin treatment on glycemic control and diabetes development risk.

The team searched the Cochrane Central Register of Controlled Trials and Medline databases for double-blinded randomized controlled trials published between January 1990 and April 2022, specifically assessing the impact of statin drugs on incident diabetes diagnoses and worsening glycemia. The study included trials of statin treatment for ≥2.0 years with ≥1,000 individuals included in the Cholesterol Treatment Trialists’ (CTT) Collaboration.

The researchers sought all reported diabetes-associated adverse events, therapies, and glycemia measures from the included trials. They evaluated the impact of statin treatment on incident diabetes and worsening glycemic control. They determined diabetes incidence by diabetes-associated adverse events, novel glucose-lowering drug usage, fasting blood glucose levels of ≥7.0 mmol/L, random blood glucose of ≥11.10 mmol/L, and glycated hemoglobin (HbA1c) values of ≥6·5%/. They ascertained worsening glycemic control among diabetic patients by glucose control complications or ketosis, increased glucose-lowering drug use, insulin initiation, or ≥0·5% increase in HbA1c levels.

The team used the inverse-variance-weighted (IVW) method to evaluate the effects of allocation to statin therapy on mean glucose concentrations and HbA1c values after assignment to a treatment group. They used rate ratios (RRs) for all statin regimens to estimate the absolute excess annual rate of incident diabetes, stratifying by baseline glycemia quartiles and incident diabetes risk scores. They performed subgroup analyses by baseline characteristics, treatment year, and various statin intensities or regimens. They mapped adverse event terms to the Medical Dictionary for Regulatory Activities and identified glucose-lowering medications using a Martindale-based drug dictionary.

Results

Of the included trials, 19 compared statin vs. placebo treatment [123,940 individuals, 21% (n=25,701) diabetics; four-year follow-up (median)], and four randomized trials compared high-intensity vs. low to moderate-intensity statin treatment (30,724 individuals, 5,340 (17%) diabetic patients; five-year follow-up (median)]. Compared to placebo treatment, allotment to low to moderate-intensity statins increased diabetic incidence by 10% [2,420 cases among 39,179 statin recipients (1.3% each year) versus 2,214 cases among 39,266 placebo recipients [1.2% annually; RR, 1.1]. Consuming high-intensity statins increased diabetes risk by 36% (1,221 of 9,935 individuals allotted to the statin therapy group (4.8% each year) versus 905 of 9,859 individuals allotted to the placebo group (3.5% each year)].

For every trial, the researchers determined the risk of incident diabetes among placebo recipients by the number of individuals with one or more follow-up glycated hemoglobin measures; this percentage was significantly higher in high-intensity statin trials than in low- to moderate-intensity statin studies. As a result, the HbA1c readings were the key predictor of the degree of absolute excess in trial types instead of the proportionate enhancement in stain therapy-related diabetes risk.

Among patients without diabetes at baseline, mean blood glucose rose by 0.040 mmol/L following statin treatment. The mean HbA1c levels rose by 0.060% and 0.080% after using statins of low- to moderate-intensity and high-intensity, respectively. Among individuals with baseline glycemia measurements, the team noted 62% of incident diabetes cases among those in the topmost quartile of baseline distributions. The relative impact of statin treatment on the incidence of diabetes was consistent across diverse populations and throughout time. Individuals with diabetes at baseline had rate ratios for worsening glycemia of 1.1 and 1.2 for low- to moderate-intensity and high-intensity statins, respectively, compared to placebo.

The study found that statins induce a modest rise in new diabetes diagnoses, particularly among individuals with baseline glycemic indicators near the diagnostic cut-offs. However, the cardiovascular risk reduction observed with statin medication surpasses any potential adverse effects. The absolute advantages of statin medication outweigh any additional hazards connected with the slight rise in glycemia they cause. The study findings should help shape clinical guidelines for managing people on statin treatment. The evidence of positive effects on major vascular events gives comfort about the overall advantages of statin medication for individuals who are at risk of acquiring or have already developed diabetes.