Statins slightly increase diabetes risk, but cardiovascular benefits remain, study finds

In a recent study published in Lancet Diabetes and Endocrinologyresearchers conducted a meta-analysis of long-term, large-scale, randomized, double-blind controlled trials to determine the effect of statin medication on worsening of blood sugar and diabetes diagnosis.

Atherosclerotic cardiovascular disease is a serious global health problem, in which diabetes plays a key role. Statins have limited side effects and may increase the incidence of diabetes compared to placebo or standard treatment. However, the lack of evidence from these meta-analyses makes it inadequate to assess the impact of statin treatment on the likelihood of developing new-onset diabetes. There is a lack of understanding of high-risk patients when additional risks occur after initiation of medication, and how statin therapy affects glycemic control in patients with established diabetes. .

study: Effect of statin therapy on diagnosis of new-onset diabetes and glycemic exacerbations in large randomized, blinded statin trials: a meta-analysis of individual participant data.. Image credit: Roger Ashford / Shutterstock

About research

In this meta-analysis, researchers investigated the effects of statin treatment on glycemic control and risk of developing diabetes.

The research team searched the Cochrane Central Register of Controlled Trials and the Medline database for double-blind, randomized controlled trials published between January 1990 and April 2022, specifically for incident diagnosis of diabetes and glycemia. The effect of statin drugs on exacerbations was evaluated. The study included trials of statin treatment over 2.0 years in over 1,000 people included in the Cholesterol Treatment Trial List (CTT) collaboration.

Researchers looked at all diabetes-related adverse events, treatments, and blood sugar levels reported from included trials. They evaluated the impact of statin treatment on the development of diabetes and worsening glycemic control. They were diagnosed with diabetes by diabetes-related adverse events, use of novel hypoglycemic drugs, fasting blood glucose levels ≥7.0 mmol/L, random blood glucose levels ≥11.10 mmol/L, and glycated hemoglobin (HbA1c) values ​​≥6. The incidence was determined. Five%/. The researchers found that glycemic control complications and ketosis, increased use of hypoglycemic drugs, insulin initiation, or an increase in HbA1c levels of 0.5% or more worsened glycemic control in patients with diabetes.

The research team used inverse variance weighting (IVW) to assess the impact of assignment to statin therapy on mean glucose and HbA1c levels after assignment to treatment groups. They estimated annual excess rates of incident diabetes using rate ratios (RRs) for all statin regimens, stratified by baseline glycemic quartile and incident diabetes risk score. They conducted subgroup analyzes by baseline characteristics, year of treatment, and different statin intensities or regimens. They mapped adverse event terms to a medical dictionary for regulatory activities and used a Martindale-based drug dictionary to identify hypoglycemic drugs.

result

Of the included trials, 19 compared statin treatment with placebo treatment. [123,940 individuals, 21% (n=25,701) diabetics; four-year follow-up (median)]and four randomized trials compared high-intensity statin treatment with low-to-moderate-intensity statin treatment (30,724 people, 5,340 (17%) patients with diabetes; median follow-up of 5 years). Assignment to low-to-moderate-intensity statin treatment compared to placebo treatment showed that moderate-intensity statins increased the incidence of diabetes 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]. Taking high-intensity statins increased diabetes risk by 36% (1,221 of 9,935 people assigned to the statin treatment group (4.8% annually) vs. 905 of 9,859 people assigned to the placebo group (3.5% annually). )].

Researchers determined the risk of developing diabetes among those receiving the placebo by the number of individuals who followed up with one or more glycated hemoglobin measurements in each trial. This rate was significantly higher in high-intensity statin trials than in low-to-moderate-intensity statin studies. As a result, HbA1c measurements, rather than the proportional increase in diabetes risk associated with staining therapy, were a significant predictor of the degree of absolute excess in trial type.

In patients without diabetes at baseline, mean blood glucose levels increased by 0.040 mmol/L after statin treatment. After using low-to-moderate-intensity and high-intensity statins, mean HbA1c levels increased by 0.060% and 0.080%, respectively. The research team noted that among individuals with baseline blood glucose measurements, 62% of diabetes cases were in the top quartile of the baseline distribution. The relative impact of statin treatment on diabetes incidence was consistent across different populations and over time. Those with diabetes at baseline had glycemic exacerbation rate ratios of 1.1 and 1.2 for low-to-moderate-intensity and high-intensity statins, respectively, compared to placebo.

This study found that statins caused a modest increase in new diabetes diagnoses, especially among individuals with baseline glycemic index near the diagnostic cutoff. However, the cardiovascular risk reduction observed with statin treatment outweighs any potential side effects. The absolute benefits of statin drugs outweigh the additional risks associated with the small increases in blood sugar that they cause. The findings should help shape clinical guidelines for managing people on statin therapy. Evidence of a positive effect on major vascular events provides reassurance about the overall benefits of statin drugs for people at risk of developing diabetes or who have already developed diabetes.