Harms of Glucose-Lowering Therapy Sometimes Outweigh Benefits

Especially in older patients, the burdens of intensive glucose-lowering treatment for type 2 diabetes—particularly with insulin—may exceed the benefits, suggests a study in JAMA Internal Medicine.

A Markov stimulation model was used to examine the impact of treatments to reduce hemoglobin A1c (HbA1c) on diabetes complication rates and quality-adjusted life-years (QALYs), based on published data. The results suggested that treatment benefits varied substantially with patient age. Assuming a low treatment burden, treatments to lower HbA1c by 1 percentage point had a net benefit of 0.77 to 0.91 QALYs for patients receiving diagnoses of type 2 diabetes at age 45, compared with just 0.08 to 0.10 QALYs for those receiving diagnoses at age 75. At a higher treatment burden (3.7 lost days per year), the harms of HbA1c-lowering therapy exceeded the benefits for 75-year-old patients.

Metformin, with relatively small treatment disutility, was beneficial across age groups: net benefit 1.2 QALYs in a 45-year-old patient and 0.148 QALYs in a 75-year-old patient. The absolute reduction in ESRD risk was nearly 10 times greater in a 45-year-old patient than in a 75-year-old patient: 0.065 versus 0.007.

In contrast, starting insulin in response to later increases in HbA1c had a negative impact on QALYs in all age groups. The absolute reduction in ESRD achieved by starting insulin at age 55 was just 0.013.

The trend in type 2 diabetes treatment has been toward intensive glycemic control with lower HbA1c targets. However, the benefits of treatment may take years to accrue, whereas the burdens and adverse effects begin much earlier.

The new study suggests that treatments to improve glycemic control are beneficial particularly for younger patients with type 2 diabetes. However, intensified treatment—especially adding insulin to metformin therapy—may be of little or no net benefit for older patients. “Thus, shared decision making, in which patient preferences are specifically elicited and considered, appears to be the best approach to making most decisions about glycemic management in patients with type 2 diabetes,” the researchers write [Vijan S, et al. Effect of patients’ risks and preferences on health gains with plasma glucose level lowering in type 2 diabetes mellitus. JAMA Intern Med June 30, 2014. doi:10.1001/jamainternmed.2014.2894].