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Targeting inflammation may provide new treatment options for diabetes


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Aruna Pradhan MD, MPH, MSc
Aruna Pradhan, MD, MPH, MSc

During Sunday’s Joint ADA/American Society of Nephrology Symposium, Aruna Pradhan, MD, MPH, MSc, reviewed research looking at inflammation as a driver for diabetes, and whether treatment with anti-inflammatory agents might reduce the risk of diabetes and atherothrombosis.

“Many of the drugs that are commonly used (for diabetes) have some evidence of impacts on anti-inflammatory pathways. As a cardiologist, what I think about is when I give someone an agent to prevent cardiovascular disease, are there secondary benefits on glycemia?” said Dr. Pradhan, Assistant Professor of Medicine at Harvard Medical School

Dr. Pradhan reviewed a study showing that the interleukin-1 beta pathway is important for glycemic control. In the double-blind, 13-week trial, researchers found a reduction in glycated hemoglobin at 13 weeks, along with a reduction that was consistent and sustained 13 weeks throughout treatment.

“Targeting this pathway works in terms of reducing glucose levels, at least in the short term,” Dr. Pradhan said.

In another trial, Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), the research team looked a variety of diabetes outcomes in a prespecified secondary analysis. They considered canakinumab’s efficacy on major adverse cardiovascular events in diabetic and non-diabetic subjects, baseline high sensitivity c-reactive protein (hsCRP) and interleukin-6 (IL-6) in new-onset diabetes, effects of canakinumab on A1C, and effects of canakinumab on new-onset diabetes in patients with pre-diabetes at trial entry.

“The first analysis demonstrated that everyone, irrespective of a diabetes classification at baseline, derived a benefit that was similar to the overall study population, or 15 to 20 percent benefit,” Dr. Pradhan said.

The study results also indicated higher hsCRP and IL-6 levels were associated with the greatest incidence of diabetes. The most provocative results, Dr. Pradhan said, involved A1C reduction.

“There is dose-dependent decrease in A1C and percentage change in A1C, but really that maximized at about six to nine months. And then during the remainder of the trial there really was no difference,” Dr. Pradhan said. “Throughout this period, you can appreciate that the higher doses had a greater suppression of A1C, so provocative but not sustained over time.”

The data on effect on new-onset diabetes also seemed to indicate an early effect that is not sustained, she added, noting that perhaps an escape of this anti-inflammatory effect is possible.

Dr. Pradhan also highlighted three cardiovascular outcome studies—Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial (REDUCE-IT), Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia (STRENGTH), Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabeTes (PROMINENT)—that focused on using triglyceride-lowering agents in mild to moderate hypertriglyceridemia. PROMINENT, she said, is looking at pemafibrate in type 2 diabetes only, with results expected in 2022.

“We hope to have results to show that this potent peroxisome proliferator-activated receptor alpha agonist reduces glycemic events, as well as the major endpoint of cardiovascular events,” Dr. Pradhan said.