Use of Statin Therapy Associated with Progression of Diabetes

Ishak A. Mansi, MD

Although statin therapy has been associated with increased insulin resistance, there are still questions on the clinical importance of increased resistance to actual care of patients with diabetes.

As a result, a recent study assessed the progression of diabetes after the initiation of statins in a national cohort of patients covered by the US Department of Veteran Affairs (VA).

Led by Ishak A. Mansi, MD, VA North Texas Health System, the team of investigators observed statin use was associated with the progression of diabetes, including a greater likelihood of insulin treatment initiation, significant hyperglycemia, acute glycemic complications, and an increased number of glucose-lowering prescriptions.

Methods

Using a retrospective, matched-cohort study that used new-user and active-comparator designs, investigators assessed statin initiative and diabetes progression in the patient population from fiscal year (FY) 2003 - FY 2015.

Patients who were considered to meet criteria were ≥30 years old at index date and regular users of the VA health system. This included ≥1 VA encounter, blood pressure and weight, VA pharmacy dispensing, and data on blood glucose, creatinine, and LDL cholesterol.

The study identified the statin user group as patients who initiated statin therapy within the study period, while the active comparator group was composed of patients who initiated an H2-blocker or proton pump inhibitor.

Further, the diabetes progression composite outcome was defined as the following: new insulin initiation or increase in number of glucose-lowering medication classes; new persistent hyperglycemia complications, including ≥5 measurements of blood glucose of 200 mg/dL, or a new diagnosis of diabetes with ketoacidosis or uncontrolled diabetes.

The team created a propensity score to match statin users and active comparators at a 1:1 ratio.Then, investigators compared the propensity score matched cohort using conditional logistic regression in calculation of odds ratios (OR) and 95% CI.

What did they find?

A total of 705,774 eligible VA patients were identified, composed of 595,579 statin users and 110,195 nonusers, leading to 83,022 matches of statin users and active comparators. The matched cohort had a mean age of 60.1 years with 78,712 men (94.9%),

Further, investigators noted 1715 (2.1%) patients were American Indian/Pacific Islander/Alaska Native, 570 (0.8%) were Asian, 17,890 (21.5%) were Black, and 56,633 (68.2 %) were White individuals.

Data show statin users had filled prescriptions for a mean of 5.3 years at a total of 12,118,523 prescriptions. In those considered nonusers, 52.176 patients (47.4%) used a statin during the study period and 58,019 (52.7%) never used a statin.

Investigators observed statin users had significantly higher odds of diabetes progression, in comparison to non-users (OR 1.37; 95% CI, 1.35 - 1.40, P <.001).

They noted each component of the composite outcome had a higher rate among statin users compared with nonusers, including glucose-lowering medication classes (OR, 1.41; 95% CI, 1.38 - 1.43), new insulin starts (OR, 1.16; 95% CI, 1.12 - 1.19), presence of persistent hyperglycemia (OR, 1.13; 95% CI, 1.10 - 1.16), and new diagnosis of ketoacidosis or uncontrolled diabetes (OR, 1.24; 95% CI, 1.19 - 1.30).

A secondary analysis observed the odds of diabetes progression were higher in statin users compared to nonusers and higher than the overall cohort (OR, 1.56 versus 1.40). Further, intensive cholesterol lowering had association with the highest odds of diabetes progression among statin users.

What are the takeaways?

Investigators noted that although the higher risk of diabetes progression after statin use may seem less consequential in comparison to cardiovascular benefit, it is worth considering the risk-benefit ratio of statin use.

“However, diabetes progression has long-term effects on quality of life and treatment burden, which warrant consideration when discussing the overall risk-benefit profile, especially when used for primary prevention,” investigators wrote.

The study, “Association of Statin Therapy Initiation With Diabetes Progression,” was published in JAMA Internal Medicine.