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The American Journal of Managed Care Special Issue: Pharmacy Benefits
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Costs Associated With Long-Acting Insulin Analogues in Patients With Diabetes
Berhanu Alemayehu, DrPH, MS; Jessica Speiser, MPH; Lisa Bloudek, PharmD, MS; and Evelyn Sarnes, PharmD, MPH
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Costs Associated With Long-Acting Insulin Analogues in Patients With Diabetes

Berhanu Alemayehu, DrPH, MS; Jessica Speiser, MPH; Lisa Bloudek, PharmD, MS; and Evelyn Sarnes, PharmD, MPH
Findings from a literature review indicate that overall costs of long-acting insulin analogues are not significantly different from those of intermediate-acting human insulin and oral antidiabetic agents.

The objective of this literature review was to evaluate the costs associated with the use of long-acting insulin analogues (LAIAs) compared with non-LAIA agents, including human insulin, oral antidiabetic drugs, and other injectable therapies, in the treatment of patients with type 1 diabetes (T1D) or type 2 diabetes (T2D).

Study Design: A systematic review of the medical literature (MEDLINE, EMBASE, Cochrane, EconLit) conducted from 2004 to 2016.

Methods: The review protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria for studies were: patients with T1D and/or T2D, LAIA intervention, and comparators, including oral antidiabetics (OADs) or neutral protamine Hagedorn (NPH). Outcomes of interest were adherence measures; economic outcomes, including total costs, cost savings, and willingness-to-pay; and cost-effectiveness or incremental cost-effectiveness analyses. Real-world costs of individual LAIAs were also evaluated and are often compared against those of other LAIAs in the economic analyses.

Results: We identified and included 117 relevant studies. Patients using LAIAs had higher drug costs than those using OADs and NPH but had neutral or reduced total and diabetes-related costs compared with patients using non-LAIAs. Use of LAIA pen-delivery systems may lead to improved adherence and reduction in costs. Patients receiving insulin glargine demonstrated higher adherence and persistence than patients on insulin detemir. Economic models suggest that LAIAs are more cost-effective than NPH for T1D; for T2D, insulin glargine is more costly than NPH but less so than insulin detemir.

Conclusions: Despite higher drug costs, the real-world overall medical costs of LAIAs are not significantly different from those of NPH in patients with diabetes. The findings may be helpful for formulary decision making for patients with diabetes in a cost-constrained environment.

Am J Manag Care. 2018;24(Spec Issue No. 8):SP265-SP272
Takeaway Points

Long-acting insulin analogues (LAIAs) are a potentially cost-effective treatment choice for patients with type 1 or type 2 diabetes compared with neutral protamine Hagedorn (NPH) and oral antidiabetic agents.
  • Despite higher drug acquisition costs, use of LAIAs is associated with neutral or reduced overall diabetes-related direct healthcare costs compared with alternative intermediate-acting human insulin, NPH.
  • Limited real-world evidence suggests that use of LAIA pen-delivery systems may improve patient adherence and reduce the frequency of hypoglycemic events.
  • Formulary decision makers may use these findings to help guide the management of patients with diabetes in a cost-constrained environment.
Diabetes is among the most common chronic medical conditions worldwide, with 422 million people affected.1 Early treatment options for the replacement of basal insulin in patients have included intermediate-acting insulins, such as neutral protamine Hagedorn (NPH). Although they are effective in the management of hyperglycemia, these agents require 2 or more daily injections, often in combination with other therapies, including mealtime insulin. Since their introduction in the early 2000s, long-acting insulin analogues (LAIAs) have become a mainstay in the long-term management of patients with type 1 diabetes (T1D) or type 2 diabetes (T2D). In contrast to intermediate-acting insulins, which generally reach the bloodstream approximately 1 to 2 hours after injection, peak 4 to 12 hours later, and are effective for about 12 to 18 hours, LAIAs reach the bloodstream up to 2 hours after injection and tend to lower glucose levels fairly evenly over a 24-hour period.2 This combination of delayed absorption and fewer peaks reduces the potential for hypoglycemic episodes3; the improved pharmacokinetic properties of the LAIAs also provide greater flexibility with regard to meals and exercise and allow for less frequent administration.3 As such, LAIAs may result in improved glycemic control and higher quality of life and treatment satisfaction, with fewer diabetic complications than with NPH, non-LAIA oral diabetic agents, and short-acting insulin.4-6 Currently, the LAIAs approved in the United States are insulin glargine (eg, Lantus, Toujeo, Abasaglar), insulin detemir (Levemir), and insulin degludec (Tresiba). LAIAs are available in multiple formulations, including prefilled pen devices and vials.

As the treatment of diabetes has become more intensive and complex, drug costs have become a substantial and increasing part of total healthcare costs. From a US payer perspective, a challenge with the increasing utilization of LAIAs within the diabetic population is the higher drug acquisition cost compared with other insulin products; analyses of retrospective data from different countries demonstrate consistently higher annual drug costs for LAIAs compared with oral antidiabetics (OADs) and with shorter-acting insulins, such as NPH.7,8 However, increased drug acquisition cost is only 1 aspect of the overall cost of care for patients treated with LAIAs. The total costs of LAIAs must also be considered when comparing them with alternative regimens; for example, the use of these may include the impact of LAIAs on overall diabetic treatment costs, direct medical costs, and consequent health outcomes, such as improvements in goal attainment, risk of chronic complications, and associated ambulatory visits and hospitalizations.

Currently available LAIAs have been studied extensively over the last 10 years, resulting in a substantial body of clinical and health economic research. However, the real-world costs of LAIAs have not been definitively examined; although a large number of studies have been undertaken, there is considerable variation in their findings. Information on the real-world costs of LAIAs, which are intertwined with clinical effectiveness, are important to healthcare providers and drug formulary decision makers in evaluating the appropriate treatment strategy for each patient with T1D and T2D.

Therefore, the present investigation evaluated the real-world costs of LAIAs in patients with diabetes through a systematic medical literature review of published interventional and observational studies. The key research questions the review sought to answer were: What economic end points have been included in randomized controlled trials with LAIAs? What economic evaluations and associated economic value have been published for LAIAs? What are the real-world health outcomes associated with LAIAs? What are the real-world adherence rates associated with LAIAs?


A systematic review of the literature evaluating the use of LAIAs in patients with T1D and T2D was conducted from January 2004 to November 2014, with a subsequent update completed in 2016 to include literature published between August 2014 and October 2016. Database sources included MEDLINE (via PubMed), EMBASE, the Cochrane Library, and EconLit. The research questions for this study were part of a broader systematic review. Publications were initially identified for this broader review using a search protocol following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. From these, the PICOS (Population, Intervention, Comparators, Outcomes, and Study design) criteria9 were used to identify studies that were relevant to the research questions in this review; a brief summary of the search strategy is shown in Table 1. Patient populations included adults with T2D and patients 6 years and older diagnosed with T1D treated with 1 or more of the following LAIAs: insulin glargine 100 units/mL (U100) (Lantus), insulin glargine 300 units/mL (U300) (Toujeo), biosimilar insulin glargine (Basaglar, Abasria/Abasaglar), insulin detemir (Levemir), and insulin degludec (Tresiba). Suitable comparators for inclusion in the review included a non-LAIA treatment for diabetes, such as an OAD or NPH, or a different LAIA as comparator. Outcomes of interest included economic outcomes, including total costs, event costs, costs avoided, cost savings, willingness-to-pay assessments, cost-effectiveness, or incremental cost-effectiveness (including cost per quality-adjusted life-year [QALY]), as well as adherence outcomes, such as medication possession ratio (MPR), persistence, or discontinuation rate. Study designs of interest were controlled clinical trials, observational studies, retrospective analyses, economic models, health technology assessments, and systematic review articles reporting adherence to or economic profiles of LAIAs.

Only English-language studies were included. Unpublished studies (including conference abstracts), nonsystematic reviews, editorials, commentaries, and letters were excluded. Nonhuman studies, theses, dissertations, and pharmacokinetic/pharmaco­dynamic studies were also excluded. Additional exclusion criteria are described in Table 1.

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