Predictors of Long-term Discontinuance with Noninsulin Antihyperglycemic Agents

Qaashif Panjwani, Mercer University College of Pharmacy

The cost-burden of diabetes to the U.S. healthcare system as of 2012 is $245 billion. The general breakdown of direct medical expenditures includes the following: hospital inpatient care (43%), prescription medications to treat complications (18%), antidiabetic agents and diabetes supplies (12%), physician office visits (9%), and nursing-residential facility stays (8%). 1

There are many microvascular and macrovascular complications of diabetes, which include the following: cardiovascular disease, neuropathy, nephropathy, retinopathy, and others. Patients with poor adherence are more likely to experience complications.2 A cohort study of type 2 diabetic patients showed that poor adherence led to statistically significant increases in A1c, blood pressure, and low-density lipoprotein (LDL). These patients had poorer outcomes with a 58% increased risk for all-cause hospitalization and 81% increased risk for all-cause mortality.

Proximal Predictors of Long-Term Discontinuance with Noninsulin Antihyperglycemic Agents4
Design Retrospective, two-group cohort, modeling study; N= 71,619
Objective To assess the relative importance of static and proximal dynamic factors in explaining long-term noninsulin antihyperglycemic agents (NAA) discontinuance in diabetic patients

 

Study Groups Continuing NAA users (n = 65,183); long-term NAA discontinuers (n = 6,436)
Methods All the patients included in the study were from a cohort of patients that were continuously enrolled in Medicare Part A, B, and D fee-for-service prescription drug plans from Jan. 2006 to Dec. 2008 with a diagnosis of type 2 diabetes. The long-term NAA discontinuers group was identified by examining claims for two or more fills of one or more different NAAs in 2007 followed by an absence of claims for the next 12 months. The last month with NAA days supply was noted as index month. The 11 months previous to the index month were utilized to assess why the medications were discontinued.

Beneficiaries who died within five months of their index month were excluded from the study.

The static factors included: age, gender, race, original reason for Medicare enrollment, low-income subsidy (LIS) status, dual eligibility, and annual counts of chronic conditions in the CMS risk adjuster all measured in 2006 for the baseline. The four categories for dynamic factors include: drug use, diabetes tests and preventative measures, services indicating treatment for diabetes complications and comorbidities (RxHCC), and Medicare use and spending.

Duration Jan. 1, 2006 – Dec. 31 2008
Primary Outcome Measure To determine the main cause of NAA discontinuation based on static and dynamic factors
Baseline Characteristics
Characteristics NAA Discontinuers NAA Continuing Users P value
Average age (years) 71.3 70.5 < 0.001
Sex (%) 0.388
Male 33.6 34.2
Female 66.4 65.8
Race (%) < 0.001
White 69.8 73.7
Black 19.2 14.9
Other 11.0 14.0
Original reason for enrollment < 0.001
65 ≥ (%) 59.5 64.6
End stage renal disease or Social Security disability insurance 40.5 35.4
LIS (%) < 0.001
Yes 72.0 66.2
No 28.1 33.8
Dual Eligibility (%) < 0.001
Yes 68.2 62.6
No 31.8 37.4
RxHCC (%) 8.6 7.3 < 0.001
 

 

 

Results

Table 1: NAA Discontinuation with Static Variable Only

Static variable

 

Adjusted probability p-value
Age 0.0003 0.031
Gender (Ref. female)
Male 0.0044 0.058
Race (Ref. white)
Black 0.0264 < 0.001
Other 0.0001 0.974
Old age as reason for enrollment -0.0148 0.001
LIS 0.0093

 

0.035
Dual eligible -0.0007

 

0.870
RxHCC 0.0085

 

< 0.001

 

Dynamic Variables NAA Discontinuers (n = 6,436) NAA Continuing Users (n = 65,183)
Month Previous to Index Month Index Month Month Previous to Index Month Index Month
-4 -3 -2 -1 0 -4 -3 -2 -1 0
Drug use variables
    NAA usage gap, % 15.89 15.78 17.22 4.36 6.39 6.39 5.97 3.95
    Different NAAs filled, n 0.7 0.8 0.6 0.8 1 1 1 1.1
    Discontinuation of ACEIs/ARBs, % 0.61 0.65 1.04 1.54 4.93 0.27 0.31 0.33 0.33 0.43
    Discontinuation of statins, % 0.36 0.62 0.73 1.09 4.81 0.28 0.26 0.29 0.31 0.35
Diabetes tests and other preventive measures, %
    A1c test 17.95 18.38 17.17 21.16 19.52 18.48 18.28 18.69 19.05 18.72
    Fasting blood glucose test 3.7 3.89 4.36 4.76 4.81 3.73 3.72 3.73 3.93 3.73
Diabetes complications and comorbidities (%)
    Uncontrolled diabetes 9.76 10.13 11.1 13.22 11.8 8.38 8.39 8.52 8.73 9.02
    Short-term diabetes complications 0.47 0.36 0.5 0.58 0.45 0.27 0.29 0.27 0.29 0.29
    Hypoglycemia 0.7 0.76 0.93 1.4 1.15 0.18 0.21 0.2 0.2 0.2
    ESRD 3.27 3.44 3.55 3.7 3.89 1.04 1.05 1.07 1.1 1.11
Medicare utilization and spending
    Hospital discharge, % 9.4 8.83 10.91 13.37 10.17 3.53 3.62 3.55 3.62 3.72
    SNF discharge, % 2.01 2.26 2.26 3.39 2.16 0.5 0.52 0.55 0.48 0.5
    Unique physicians seen, n 2.1 2.1 2.3 2.5 2.2 1.2 1.2 1.2 1.2 1.2
    Part D spending, $ 403.35 420.29 395.33 434.64 383.69 357.41 357.82 364.02 369.03 372.7

 

Study Author Conclusions In this study, multiple dynamic and static variables have been analyzed to determine preceding discontinuance with NAA therapy. Realizing dynamic factors play an important role in adherence, new avenues for investigating and intervening can be focused on dynamic variables.

 

 

 

One of the main concerns in treating diabetic patients is adherence to their medication regimens. As seen from the study summarized, static variables were not significant at predicting discontinuation of NAA in comparison to the dynamic variables. Medicare enrollees are constantly going through transitions of care between inpatient hospital stays and skilled nursing facilities; therefore, it is concerning to learn that plays a significant impact on discontinuation of NAAs.

As the direct and indirect cost of diabetes continues to increase, it will be important to analyze what factors can be controlled in order to reduce this economic burden. Understanding key determinants that lead to discontinuation of NAA can help lead to targeted interventions such as motivational interviewing at discharge. Along with motivational interviewing, general counseling about NAAs are crucial for patients to understand and believe in the medication as that will help with adherence to their regimens. By increasing medication adherence to NAA, hopefully the cost-burden of complications due to prolonged uncontrolled diabetes can decrease over time.

 

References:

  1. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013;36(4):1033-46.
  2. Available at: http://www.mayoclinic.org/diseases-conditions/diabetes/basics/complications/con-20033091. Accessed September 15, 2016.
  3. García-pérez LE, Alvarez M, Dilla T, Gil-guillén V, Orozco-beltrán D. Adherence to therapies in patients with type 2 diabetes. Diabetes Ther. 2013;4(2):175-94.
  4. Stuart BC, Shen X, Quinn CC, et al. Proximal Predictors of Long-Term Discontinuance with Noninsulin Antihyperglycemic Agents. J Manag Care Spec Pharm. 2016;22(9):1019-27.
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