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Evidence-Based Diabetes Management September 2019

Impact of Switching Analogue Insulin to Human Insulin in Diabetes

Kyunghwa Park, PharmD; Angela Eng Jeong, PharmD; Eric Guenther-Gleason, PharmD, MS; and Sachin H. Jain, MD, MBA
Converting from analogue insulin to human insulin is associated with a clinical insignificant increase in glycated hemoglobin of 0.16% but with improved insulin adherence.
ABSTRACT                                    
Objectives: Costly analogues limit affordability in patients, leading to medication nonadherence and worsening diabetes complications. Evaluating the insulin conversion from analogues to human insulin may determine if this cost savings contributed less toward the initial coverage limit while assessing its impact on glycated hemoglobin (A1C) and medication adherence.

Study Design: Retrospective and descriptive analysis of patients with type 2 diabetes.

Methods: Patients who filled ≥1 insulin prescription between January 1, 2013, and December 31, 2018, were included. No exclusions applied. The primary outcomes assessed percent of human insulin prescribed, cost of both insulins, insulin costs per user, and average last A1C per year. The secondary outcome assessed medication adherence. Outcomes were obtained from pharmacy claims and lab data and compared as pre-insulin conversion (2013-2014), insulin conversion (2015-2016), and postinsulin conversion (2017-2018) periods.

Results: The percentage of human insulin decreased from 11% in 2013 to 10% in 2014 (pre-intervention), increased from 24% in 2015 to 68% in 2016 (intervention), and further increased to 69% in 2017 before dropping to 68% in 2018 (post intervention). Insulin costs per user were $2658.07 in 2013, $3332.65 in 2014, $3119.34 in 2015, $2264.78 in 2016, $2446.78 in 2017, and $2842.10 in 2018. The average last A1C increased by 0.16% from 2013 to 2018. The medication possession ratio ranged from 79% to 86% from 2013 to 2018.

Conclusions: The insulin conversion was associated with a clinically insignificant 0.16% increase in the average last A1C from 2013 to 2018 but improved adherence. Insulin cost did not contribute as much toward the initial coverage limit after 2016.

 
Take-Away Points
The high cost of analogue insulin affects healthcare spending and negatively impacts patients by limiting affordability, worsening medication adherence, and leading to microvascular and macrovascular complications. Human insulin is a more cost-effective alternative to expensive analogues, yet analogues are often used for a basal-prandial strategy by many providers. Through this claims analysis that evaluated the insulin conversion from analogues to human insulin since 2015, we found that:
  • Cost-savings helped prevent or delay reaching the coverage gap, or “donut hole”
  • There was a clinically insignificant increase in the average last glycated hemoglobin of the year by 0.16%
  • Medication possession ratio continued to increase from 83% to 86%
Introduction
Approximately 629 million people are projected to have diabetes by 2045, which constitutes a 48% increase from 2017 to 2045.1 Insulin is considered the most effective medication to achieve glucose control and avoid further complications in patients with diabetes.2 However, 1 in 2 people needing insulin lack access globally. High prices and lack of availability are thought to be key contributors to poor insulin access.1

Studies comparing the clinical efficacy of analogue insulin to human insulin are scarce. The American Diabetes Association Standards of Medical Care in Diabetes-2019 currently does not provide guidance for analogues versus human insulin. The guideline states that once-daily basal insulin injection therapy is associated with minimal adverse effects while multiple daily injections may be too complex for older patients.3 The only differentiation made between the 2 insulins by the ADA is the high cost of analogues and the low cost of human insulin. In addition, Fullerton et al’s systematic review comparing short-acting analogue insulin versus regular human insulin in adults with type 2 diabetes (T2D) demonstrated no clear benefit of short-acting analogue insulin over regular human insulin.4

CareMore Health, a care delivery system, examined its insulin spending in 2014. The organization found that its Medicare Advantage patients were using analogues that had a high daily injection burden (ie, basal-prandial insulin strategies) and were reaching the Medicare Part D coverage gap.5

In February 2015, CareMore started a protocol-driven intervention to switch from higher-cost analogues to lower-cost human insulin in patients with T2D led by clinical pharmacists at various Comprehensive Care Clinics. Patients who were on both basal and prandial insulin receiving at least 50 units/day, without any history of hypoglycemia and adherent to insulin, were eligible for the conversion. Clinical pharmacists determined the total daily dose (TDD), discontinued the basal and prandial insulins and other secretagogues, and converted to premixed insulin by 20% less than the calculated TDD. Patients were given two-thirds of TDD at breakfast and one-third of TDD at dinner then titrated to target predinner glucose and fasting glucose, respectively. The implementation of the insulin conversion program was further supported by other healthcare providers with experience in chronic disease management.5

By encouraging patients to use human insulin, this pilot program led to preference for regimens containing fewer daily injections and a delay in reaching the Medicare Part D coverage gap. The insulin switch was found to be associated with a small increase in population-level A1C of 0.14%, and the intervention was not associated with changes in rates of serious hypoglycemia or hyperglycemia.5 Our study further aims to assess the impact of insulin conversion through descriptive analysis in order to determine if this cost savings contributed less toward the initial coverage limit. Overall, this study is an update from the original findings demonstrated by Luo et al,5 in which the average last A1C for the year and medication adherence were also evaluated from 2013 to 2018.

Methods
Any patients who filled ≥1 insulin prescription between January 1, 2013, and December 31, 2018, were eligible for this study. No exclusions were applied. The primary objectives were to assess the percent of human insulin (calculated from the normalized prescriptions of both insulins), the cost of insulin therapy, insulin costs per user, and the average last A1C per year. The secondary objective was to assess if there was improvement in insulin adherence. Adherence was calculated using medication possession ratio (MPR) based on days supply of basal or mixed insulin. All data were obtained from pharmacy claims and lab data from 2013 to 2018. The overall trends in primary and secondary outcomes were compared in 3 study periods: pre-insulin conversion (2013-2014), insulin conversion (2015-2016), and postinsulin conversion (2017-2018).

The implementation of the insulin switch program at CareMore was part of the QI project and therefore, no internal review board approval was necessary.

Results
Pre-Insulin Conversion Period (2013-2014)
The total normalized prescriptions filled for both insulins increased from 96,968 in 2013 to 101,298 in 2014, which consisted of only 11% and 10% of human insulin prescriptions being filled, respectively (Figure). The combined cost of both insulins was $25,336,724 in 2013 and $33,936,348 in 2014; the insulin costs per user were $2658.07 and $3332.65, respectively. The average last A1C was 8.06% in 2013 and 8.02% in 2014 while the MPRs were 80% and 81%, respectively (Table).

Insulin Conversion Implementation Period (2015-2016)
The total normalized prescriptions filled for both insulins decreased from 98,779 in 2015 to 85,755 in 2016. Human insulin prescriptions rose from 24% to 68% in this same timeframe (Figure 1). The combined cost of both insulins was $32,880,942 in 2015 and $21,893,628 in 2016, and the insulin costs per user were $3119 and $2265, respectively. The average last A1C was 8.17% in 2015 and 8.31% in 2016, while the MPRs were 79% and 83% (Table 1).

Postinsulin Conversion Period (2017-2018)
The total normalized prescriptions filled for both insulins increased from 90,376 in 2017 to 92,352 in 2018. During this period, 69% and 68% of insulin prescriptions were for human insulin in 2017 and 2018, respectively (Figure 1). The combined cost of both insulins was $24,164,374 in 2017 and $29,313,460 in 2018 while the insulin costs per user were $2446.78 and $2842.10 . The average last A1C was 8.23% in 2017 and 8.22% in 2018, while the MPRs were 85% and 86% (Table 1).

Discussion
Pre-Insulin Conversion Period (2013-2014)
There was an increase in the number of normalized prescriptions filled, but only 11% and 10% were for human insulin in 2013 and 2014, respectively. In 2013, the insulin cost per user was $2658.07 while the initial coverage limit was $2970. However, the costs of some analogue insulins increased in 2014, and the total insulin cost per user increased to $3332.65 while the initial coverage limit was only $2850. This cost suggests that the majority of insulin users would have reached the Medicare Part D coverage gap from insulin use alone. This was the issue that created a need for the pilot program. At this time, a higher percentage of analogues were prescribed and a majority of the clinicians were still practicing the basal-prandial strategy.

Insulin Conversion Implementation Period (2015-2016)
There was a sharp drop in analogue use. From 2015 to 2016, human insulin prescriptions jumped from 24% to 68%. This abrupt increase was expected due to the insulin conversion project. In addition, the total cost of insulin decreased substantially, from $32,880,942 in 2015 to $21,893,628 in 2016 due to the more cost-effective human insulin being prescribed. The insulin cost per user also decreased from $3119.34 in 2015 to $2264.78 in 2016. Because the initial coverage limit in 2015 was $2960, patients were already falling into the Medicare Part D coverage gap, from insulin prescriptions alone. However, the initial coverage limit in 2016 was $3310, and insulin users were more likely to avoid reaching the coverage gap due to the increased use of more cost-effective insulin. In addition, in January 2016, select plans moved the analogue products containing glargine, detemir, or aspart from tier 6 ($0 copay) to tier 3 ($37.50 copay for most patients, with additional out-of-pocket payments if patients were in the Medicare Part D coverage gap), while human insulin products remained on a tier with a $0 copay.5 This formulary change may have also influenced the providers to prescribe less of the costly analogues.

Postinsulin Conversion Period (2017-2018)
During the postconversion period, there was an increase in total normalized prescriptions, while human insulin prescriptions remained relatively stable at 68% to 69%. This suggests that the implementation of the insulin conversion had been sustained since 2015. Similarly, the insulin cost per user remained low at $2446.78 and $2842.10 in 2017 and 2018, respectively. As the initial coverage limit also increased to $3700 in 2017 and $3750 in 2018, more insulin users were able to delay reaching the Medicare Part D coverage gap. The rise in cost during this timeframe may be attributed to 2 formulary changes made for 2018. ReliOn insulin, a lower-cost human insulin, was removed from the formulary. Furthermore, human insulin pens were introduced to the formulary and are more costly than the vials.

Impact on A1C
The average last A1C levels ranged from 8.02% during the pre-intervention period in 2014 to 8.31% during the intervention period in 2016. The average last A1C levels during the postintervention period also remained relatively stable, at 8.22% to 8.23%. This suggests that there was only a 0.16% increase in the average last A1C over the previous 5 years, which is similar to Luo et al’s finding of population-A1C level increase by 0.14% from the insulin switch.5 Since change in A1C by 0.5% has been suggested to be clinically meaningful, this study’s results also suggest that the insulin conversion is associated with a clinically insignificant increase in A1C level.

Adherence to Insulin Therapy
There was an overall increase in MPR from 79% to 86% from 2013 to 2018. The continuously rising MPR—79% in 2015 to 83% in 2016 to 85% in 2017 to 86% in 2018—suggests that the improvement in insulin adherence may be attributed to the conversion intervention after 2015.

Limitations
Limitations to this study include no data on the rate of hypoglycemia and hyperglycemia to suggest whether the insulin switch increased the prevalence of serious hypoglycemic and hyperglycemic events since 2016. This study also does not evaluate average daily injections or overall patient satisfaction as a result of the potential reduction in number of daily injections from switching from analogue to human insulin.

Conclusions
This study’s results further demonstrated the impact of cost savings, the average last A1C for each year, and medication adherence after the conversion from analogue insulin to human insulin between 2013 and 2018. Clinical pharmacists’ efforts in researching, developing, and implementing this pilot project in 2015 helped to reduce the cost barrier to insulin and delayed reaching the Medicare Part D coverage gap each year from 2016 to 2018.

Acknowledgements
The authors would like to thank Jim Rose, PharmD, Ani Davis, PharmD, and Balu Gadhe, MD (along with Sachin H. Jain, MD, MBA) as part of the initial team to launch the insulin conversion program in 2015. The authors would also like to thank the current clinicians (clinical pharmacists, nurse practitioners, physician assistants, and physicians) at CareMore Health for sustaining the insulin implementation since 2015.
 
Author Information
Kyunghwa Park, PharmD; Angela Eng Jeong, PharmD; and Eric Guenther-Gleason, PharmD, MS; are all employed by CareMore Health, Cerritos, California.
Funding. None
 
References
  1. Ewen M, Joosse JH, Beran D, Laing R. Insulin prices, availability and affordability in 13 low-income and middle-income countries. BMJ Glob Health. 2019;4(3):e001410. doi: 10.1136/bmjgh-2019-001410. eCollection2019.
  2. Perez-Nieves M, Jian D, Eby E. Incidence, prevalence, and trend analysis of the use of insulin delivery systems in the United States (2005 to 2011). Curr Med Res Opin. 2015;31(5):891-899. doi: 10.1185/03007995.2015.1020366.
  3. American Diabetes Association. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes – 2019. Diabetes Care. 2019;42(suppl 1): S90-S102. doi: 10.2337/dc19-S009.
  4. Fullerton B, Siebenhofer A, Jeitler K, et al. Short-acting insulin analogues versus regular human insulin for adult, non-pregnant persons with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2018;12:CD013228. doi: 10.1002/14651858.CD013228.
  5. Luo J, Khan NF, Manetti T, et al. Implementation of a health plan program for switching from analogue to human insulin and glycemic control among Medicare beneficiaries with type 2 diabetes. JAMA. 2019;321(4):374-384. doi: 10.1001/jama.2018.21364.


 
 
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