Significant HbA1c Lowering in Patients Achieving a Hepatitis C Virus Cure

Discussion

The immediate reduction in HbA_1c following HCV treatment observed in this study of -0.67% is clinically significant and contrasts with the expected rise in HbA_1c seen with normal disease progression. The results from this study are comparable to HbA_1c reductions seen with certain oral, antihyperglycemic medications, such as DPP-4 inhibitors, meglitinides, and SGLT-2 inhibitors that have an average HbA_1c lowering of 0.5% to 1%. This effect was increasingly magnified in patients with a higher baseline HbA_1c.

The sustained effect on HbA_1c may have not been seen in the overall cohort achieving SVR12 due to the fairly well-controlled mean baseline HbA_1c for this older patient cohort. In addition to improvements in HbA_1c, one-third of patients achieving SVR12 required de-escalation of concomitant antihyperglycemic medications. The de-escalation of antihyperglycemics may have made the sustained HbA_1c impact underappreciated in the overall cohort. There were also limited sustained HbA_1c data to evaluate at the time the review was completed.

Despite the clinically significant magnitude of HbA_1c change, this study suggests that this effect is not predictable for all patients with DM achieving SVR12 from HCV treatment. Nineteen percent (28/147) of these patients neither had a decrease in their HbA_1c nor a de-escalation of their antihyperglycemic treatment. Patients whose T2DM onset preceded or was independent of the diabetogenic effects of HCV may be more likely to have insulin resistance unaffected by hepatitis C viral clearance. Notably, the small number of treatment relapses in this study limits this group’s ability to serve as a comparator. However, one may expect a treatment relapse to have an initial decrease in insulin resistance while the hepatitis C viral load decreases below the level of detectability, yet the effects not be sustained once the HCV relapses.

Of the 35 patients who had their HbA_1c decrease to < 6% following HCV treatment, concerningly 29 (83%) had either no change or even had an escalation in their antihyperglycemic regimen. This lack of de-escalation occurred despite 45% (13/29) of these patients continuing insulin posttreatment. These patients may be at a particularly high risk for hypoglycemia. Given the mean age of patients was 62 years, extremely tight glycemic control typically is not the goal for this older patient population with numerous comorbidities and high potential for hypoglycemia unawareness.

This raises concerns that patients with T2DM undergoing HCV treatment experience a new heightened risk of hypoglycemia, particularly if neither patients or providers managing DM are aware of the high potential for decreased antihyperglycemic needs upon achieving hepatitis C virologic response. It is important that these providers are aware of the mean decreased insulin resistance achieved from hepatitis C viral clearance. Providers managing DM should advise frequent serum blood glucose monitoring with close follow-up to allow for medication adjustments to prevent hypoglycemic episodes occurring during and after HCV treatment.

Limitations

The limitations of this study included small sample sizes in subgroups, and the retrospective design prohibited the ability to quantify and describe hypoglycemic events that may have occurred as a result of HCV treatment. In addition, the documentation of medication changes in CPRS may not have fully accounted for adjustments or self-discontinuations of DM medications. An alternative definition for change in antihyperglycemic medications may have accounted for the variable HbA_1c-lowering between oral antihyperglycemic medications.