Are clinicians intensifying treatment before it is too late?
According to American Diabetes Association (ADA) guidelines, patients with type 2 diabetes (T2D) should receive treatment intensification if there is no improvement in glycated hemoglobin levels (HbA1c) after 3 months of initial pharmacotherapy with metformin. Several small observational studies that explored the concept of treatment intensification among patients with T2D and poor glycemic control have shown inconsistent results.1,2 The present study by A.Z. Fu, et al, is a retrospective cohort of adult patients in the U.S. with uncontrolled T2D designed to evaluate time to treatment intensification after receiving 3 months of initial first line therapy.
A large United States insurance claims database (Truven Health MarketScan), Medicare claims database, and laboratory databases were used to identify prescriptions filled and HbA1c values for eligible patients over a 12-month period between January 2009 and December 2013. The patients included were over the age of 18 with a T2D diagnosis and treatment failure defined as HbA1c of 8% or greater after receiving 3 months of metformin monotherapy or combination therapy including metformin. Continuous enrollment in the database for a minimum of 12 months prior to the start of the study and 12 months after for follow up was required. Patients with a diagnosis of type 1 diabetes or polycystic ovary syndrome, and prescriptions for any injectable diabetes medication before the start of the study were excluded. Mean age of the study population was 57 and the mean index HbA1c was 9.1%. Notable baseline characteristics were 63.2% of patients were from the southern region of the US and 74% of patients in the cohort had no other reported comorbidities (Charlson index score of less than 0). The primary outcome of this study was to evaluate time to treatment intensification as defined by patients filling a prescription of additional diabetic medications over a 12-month period. Therapy choices in treatment intensification were also explored.
After screening and exclusion, 11,525 patients were included in the final cohort. Treatment intensification was categorized into three groups: early (within 6 months of treatment failure), late (6-12 months), and never intensified over the 12-month period. Only 37% of patients had early intensification, 11% late, and 52% were never intensified. Cox multivariable analysis of time to treatment intensification showed that patients with an HbA1c>10% were significantly associated with early intensification when compared to lower HbA1c levels between 8 and 9% [HR 1.18, 95% (CI 1.11-1.27) for HbA1c >9 to <10% and HR 1.41, 95% (CI 1.32-1.50) for HbA1c > 10%]. Early intensification was also associated with the number of baseline outpatient visits (HR 1.005 per additional visit, 95% CI 1.002-1.009). Addition of sulphonylurea agents were the first choice in both early and late intensification groups (41.1% and 31.2% respectively). Insulin was added in 22.4% of the early intensification group and 30.2% in the late intensification group.
Limitations of this study include potential bias due to lack of stratification of patient’s race and socio-economic status. The data source utilized only captures prescriptions filled, not medications prescribed, therefore providers may have intended to intensify treatment and the patient may have never filled their prescription. Hypoglycemic risk was also not calculated in the cohort. Results may not be generalizable to all diabetes patients due to the relatively young and healthy cohort. Strengths of this study include the utilization of the largest administrative claims database available in the U.S., the lack of stringent exclusion criteria, and a long follow-up period of one year.
Although nonrandomized retrospective cohort study is limited by lack of stratification by race and socioeconomic status, and unable to account for prescriptions written by providers but never filled by the patient, the results demonstrate a clear lack of treatment intensification in a large cohort population drawn from the largest administrative claims database available in the U.S. More exploration is needed to study the barriers to treatment intensification, and identify effective solutions to reduce these barriers.
- Over a 12-month period, glucose-lowering therapy was not intensified in 52% of patients with inadequate glycemic control.
- Treatment intensification is often delayed until the HbA1c is at a higher level of 9-10%.
- Patient follow-up and adherence to outpatient visits are crucial to maintaining appropriate HbA1c targets.
Fu AZ, Sheehan JJ. Treatment intensification for patients with type 2 diabetes and poor glycaemic control. Diabetes Obes Metab. 2016 Sep;18(9):892-8.
McCoy RG, Zhang Y, Herrin J et al. Changing trends in type 2 diabetes mellitus treatment intensification, 2002-2010. Am J Manag Care 2015; 21: e288–e296. 5.
Lin J, Zhou S, Wei W, Pan C, Lingohr-Smith M, Levin P. Does clinical inertia vary by personalized a1c goal? A study of predictors and prevalence of clinical inertia in a us managed care setting. Endocr Pract 2016; 22: 151–161.
Researched and prepared by Julie Kelly, URI College of Pharmacy Pharm.D. Candidate, Class of 2017. Reviewed by Michelle Caetano, Pharm.D., BCPS, BCACP, CDOE, CVDOE.