Statins Tied to Diabetes Progression

Jim Kling

October 07, 2021

Statin use is associated with increased likelihood of diabetes progression, according to a new matched cohort analysis of data from the Department of Veteran Affairs.

Patients with diabetes who were on statins were more likely to begin taking insulin, become hyperglycemic, and to develop acute glycemic complications, and they were also more likely to be prescribed medications from more glucose-lowering drug classes.

Although previous observational and randomized, controlled trials suggested a link between statin use and diabetes progression, they typically relied on measures like insulin resistance, hemoglobin A1c, or fasting blood glucose levels. The new work, however, outlines changes in glycemic control.

The differences between fasting glucose levels and A1c levels were generally smaller than the differences in insulin sensitivity. But A1c and fasting glucose may underestimate a potential effect of statins, since physicians may escalate antidiabetes therapy in response to changes.

Insulin sensitivity is also rarely measured in real-world settings. "This study translated findings reported on academic studies of increased insulin resistance associated with statin use in research papers into everyday language of patient care. That is, patients on statins may need to escalate their antidiabetes therapy and there may have higher occurrences of uncontrolled diabetes events," lead author Ishak Mansi, MD, said in an interview.

The study was published online in JAMA Internal Medicine.

Mansi, who is staff internist at the VA North Texas Health System and a professor of medicine and data and population science at the University of Texas, both in Dallas, cautioned about overinterpretation of the findings. "This is an observational study; therefore, it can establish association, but not causation."

No Reason to Turn Down Statins

Mansi noted that it's important to distinguish between those being prescribed statins as a primary preventive measurement against cardiovascular disease, and those starting statins with preexisting cardiovascular disease for secondary prevention. Statins are a key therapeutic class for secondary prevention. "Their benefits are tremendous, and we should emphasize that no patient should stop taking their statins based on our study — rather, they should talk to their doctors," said Mansi.

The study is one of few to look at statin use and diabetes progression in patients who already have diabetes, and the first with a propensity-matched design, according to Om Ganda, MD, who was asked for comment. The results should not deter physicians from prescribing and patients from accepting statins. "Statins should not be withheld in people with high risk of cardiovascular disease, even for primary prevention, as the risk of progression of glucose levels is relatively much smaller and manageable, rather than risking cardiovascular events by stopping or not initiating when indicated by current guidelines," said Ganda, who is the medical director of the Lipid Clinic at the Joslin Diabetes Center and an associate professor of medicine at Harvard Medical School, both in Boston.

It's possible that statins could increase risk of diabetes progression through promoting insulin resistance, and they may also reduce beta-cell function, which could in turn reduce insulin secretion, according to Ganda.

The study group included 83,022 pairs of statin users and matched controls, of whom 95% were men; 68.2% were White; 22% were Black; 2.1% were Native American, Pacific Islander, or Alaska Native; and 0.8% were Asian. The mean age was 60 years.

Some 56% of statin users experienced diabetes progression, compared with 48% of control patients (odds ratio, 1.37; P < .001). Progression was defined as intensification of diabetes therapy through new use of insulin or increase in the number of medication classes, new onset chronic hyperglycemia, or acute complications from hyperglycemia.

The association was seen in the component measures, including an increased number of glucose-lowering medication classes (OR, 1.41; < .001), the frequency of new insulin use (OR, 1.16; < .001), persistent glycemia (OR, 1.13; < .001), and a new diagnosis of ketoacidosis or uncontrolled diabetes (OR, 1.24; < .001).

There was also a dose–response relationship between the intensity of LDL cholesterol-lowering medication and diabetes progression.

More Research Needed

The findings don't necessarily have a strong clinical impact, but the researchers hope it pushes toward greater personalization of statin treatment. The benefits of statins have been well studied, but their potential harms have not received the same attention. Mansi hopes to learn more about which populations stand to gain the most for primary cardiovascular disease prevention, such as older versus younger populations, healthier or sicker patients, and those with well-controlled versus uncontrolled diabetes. "Answering these questions [would] impact hundreds of millions of patients and cannot be postponed," said Mansi. He also called for dedicated funding for research into the adverse events of frequently used medications.

Mansi and Ganda have no relevant financial disclosures.

JAMA Intern Med. Published online October 4, 2021. Abstract

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