T2D/CKD Patients Have Higher Hypoglycemia Risk on Insulin

Salt Lake City—Recent research raises concerns about the widespread use of insulin therapy in T2D patients with advanced CKD.

The report in BMC Nephrology pointed out that "contrary to widely held assumption that advanced CKD is associated with decreased need for insulin, we found that insulin use was greater in T2D patients with more advanced CKD. Furthermore, this study also found that both insulin use and CKD are independent factors for risk of hypoglycemia, with patients with advanced CKD who use insulin being at the highest risk for a hypoglycemic event."

Researchers and colleagues from the University of Utah Health Sciences in Salt Lake City, Utah, called for randomized, controlled trials to determine the safety of insulin compared to newer glycemic agents in patients with T2D and advanced CKD.

The study emphasized that compared with patients with preserved kidney function and not on insulin, insulin users who had an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m² faced a nearly 5.3-fold higher risk of dangerous hypoglycemia.

Researchers reached their conclusions by analyzing records of a national cohort of 855,133 veterans with T2D seen at Department of Veterans Affairs clinics between January 1, 2008, and December 31, 2010, with at least two serum creatinine measurements. Data on insulin use were pulled from pharmacy records, and ICD-9/10 codes came from emergency room visits or hospitalizations that occurred until December 31, 2016.

The participants' mean age was 66 ± 11 years and 97% were men; their mean baseline eGFR was 73 ± 22 mL/min/1.73 m².

With 653,200 patients without insulin use at baseline, researchers determined that the eGFR <30 group had higher hazard (HR 1.80, 95% CI 1.74-1.88) of subsequent insulin use compared with the eGFR >90 group. Using a model with propensity-score matching for baseline insulin use in 305,570 patients, they determined that both insulin use (HR 2.34, 95% CI 2.24-2.44) and advanced CKD (HR 2.28, 95% CI 2.07-2.51 for comparison of eGFR <30 to eGFR >90 mL/min/1.73 m² groups) were linked with an increased risk of subsequent serious hypoglycemic events.

"In T2D, more advanced CKD was associated with greater insulin use. Both insulin use and advanced CKD were risk factors for serious hypoglycemic events," the authors concluded. "The safety of insulin compared to newer glycemic agents in more advanced CKD needs further study."

Background information in the article advised that more than 30 million adults in the United States have diabetes mellitus, which is the leading cause of CKD. In fact, nearly one in three diabetes patients develop kidney disease.

The authors added, "Despite the public health importance of kidney disease in persons with type 2 diabetes (T2D), there is a paucity of data on optimal treatment for glycemic control in this population. Fundamental questions such as the role of insulin in glycemic control in CKD still need to be addressed."

The researchers pointed out that—while it is often assumed that insulin requirements go down with advanced CKD because insulin is cleared by the kidney—cross-sectional studies indicate higher insulin use in patients with more advanced CKD. "Therefore, it remains unclear whether the need for insulin is decreased or increased in advanced CKD," they added. "A serious adverse effect of insulin therapy is hypoglycemia that results in emergency room visit or hospitalization. While insulin therapy is a known risk factor for hypoglycemic episodes, whether advanced CKD by itself is associated with increased risk of hypoglycemia has been controversial."

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