Treatment deintensification uncommon in type 2 diabetes

Many adults with type 2 diabetes may continue to receive intensive glucose control when the risks outweigh the benefits, according to a recent study.

Researchers conducted a population-based retrospective cohort study using a nationwide U.S. database to look at the frequency of treatment deintensification in adults with type 2 diabetes and determine whether it varied by glycemic control and health status. Patients were followed until death, until termination of medical insurance, or until Dec. 31, 2010. Maximum follow-up was six years. Patients were classified as being relatively healthy (two or fewer chronic conditions), having multiple comorbidities (three or more chronic conditions), or being frail (clinical notations of malnutrition, abnormal weight loss, difficulty walking, falls, decubitus ulcer, end-stage renal disease requiring dialysis, heart failure requiring hospitalization in the past year, chronic obstructive pulmonary disease requiring hospitalization in the past year, or metastatic cancer). The last recorded HbA1c for each patient was used as the index HbA1c.

Treatment deintensification was defined as discontinuation or dosage decrease of at least one glycemic medication in the 120 days after the index HbA1c measurement with no addition of or increase in dose of another glycemic medication. For patients taking insulin, deintensification was defined as a switch from short- and long-acting insulin to long-acting insulin alone or no insulin. The researchers also compared deintensification rates for patients who had an index HbA1c below 6.0% before and after February 2008, when the American Diabetes Association issued a practice advisory about increased mortality in the intensive glucose control arm of the ACCORD trial. Deintensification rates were also compared for patients who were taking at least three glycemic drugs and patients who were taking one or two. Study results were published online on April 17 by Circulation: Cardiovascular Quality and Outcomes.

A total of 99,694 patients who had type 2 diabetes and were being treated with glycemic agents were included in the study. Their mean age was 54 years. Overall, at one year of follow-up, 12,921 (13.0%) had an HbA1c below 6%, 19,670 (19.7%) had an HbA1c of 6.0% to 6.4%, 35,012 (35.1%) had an HbA1c of 6.5% to 7.5%, and 32,091 (32.2%) had an HbA1c above 7.5%. Most patients were taking one or two glucose-lowering medications (50.2% vs. 32.7%, respectively), while 17.1% were taking more than three drugs. Although most patients were considered relatively healthy (77.3%), 10.6% had multiple comorbid conditions and 12.0% were considered frail. Glycemic therapy was deintensified in 18.3% of patients after the index HbA1c, (20.6% of those with HbA1c <6%, 17.3% of those with HbA1c of 6.0 to 6.4%, 17.7% of those with HbA1c of 6.5% to7.5% and 18.6% of those with HbA1c >7.5%). Deintensification occurred more often in frail patients (21.2%) and patients with multiple comorbid conditions (19.4%) than those who were relatively healthy (17.7%) (P<0.0001 for both comparisons). No gradient in deintensification was seen across glucose levels, even after exclusion of patients being treated with metformin alone. In patients with an index HbA1c below 6.0%, 22.5% had treatment deintensification before February 2008 and 19.5% had treatment deintensification afterward (P<0.001).

The researchers noted that the data used for the study may not have captured all comorbid conditions, that clinicians may have had valid reasons for treating to a particular HbA1c level regardless of comorbid conditions, and that rates of deintensification may have been underestimated due to lack of information on insulin doses and specific dosing instructions given to patients taking oral medications, among other limitations. However, they concluded that in this cohort, deintensification of glycemic therapy did not differ widely across HbA1c values and fewer than 25% of adults whose HbA1c levels were below 6.5% had their glycemic medications reduced, even if they were frail or had multiple comorbid conditions. In addition, rates of deintensification did not change markedly after February 2008. “Increased attention to the potential hazards of overtreatment will improve physician awareness of this issue, but deintensification of long-term therapy is the next frontier for improving care quality,” the researchers wrote.

The authors of an accompanying editorial noted that the results of the current study confirm previous research finding that deintensification of diabetes treatment is uncommon in all patients regardless of health status, comorbid conditions, or glycemic control and highlight the fact that potential overtreatment of diabetes is a widespread issue. They wrote that it was surprising that deintensification rates were only slightly higher in frail patients, since this group is unlikely to benefit from intensive glycemic control and is at high risk for hypoglycemia.

The editorialists pointed out that while the American Diabetes Association recommends a personalized approach to diabetes management that considers numerous patient factors, this framework “is in opposition to disease-specific performance measures that reward achieving specific HbA1c values.” Evidence, however, now shows that diabetes treatment is associated with measureable harms and is rarely deintensified despite risks for adverse events, the editorialists said. “Creative approaches are needed to generate evidence for personalized diabetes management that acknowledges the heterogeneity of the population of patients with diabetes mellitus, as well as the dynamic, time-varying balance of net clinical benefits and harms associated with treatment,” they wrote.