Pharmacoeconomic evaluation of dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus: a systematic literature review.

INTRODUCTION: Dipeptidyl peptidase-4 inhibitors (DPP-4i) are widely used oral antidiabetic agents that exert antihyperglycemic effects in type 2 diabetes mellitus (T2DM) without increased risk of weight gain or hypoglycemic events. The objective of this paper was to systematically review the latest evidence that was associated with the pharmacoeconomic evaluation of DPP-4i for the treatment of patients with T2DM. AREAS COVERED: We conducted a systematic literature search of eligible articles published since inception up to March 2021 in Web of Science, MEDLINE (via PubMed), and ECONLIT. Fifty-four eligible articles were included in our review, in which DPP-4i were compared to metformin (4 studies), sulphonylurea (SU) (16 studies), alpha-glucosidase inhibitors (AGI) (3 studies), thiazolidinediones (TZD) (4 studies), other DPP-4i (3 studies), sodium-glucose co-transporter-2 inhibitors (SGLT-2i) (10 studies), glucagon-like peptide 1 receptor agonist (GLP-1RA) (18 studies), insulin (5 studies), and other antidiabetic therapies (5 studies). EXPERT OPINION: This study provided the updated evidence of systematic pharmacoeconomic evaluation associated with DPP-4i for the treatment of patients with T2DM. The evidence from the literature suggested that DPP-4i may be more cost-effective compared to SU and insulin as second-line therapy after metformin but not a cost-effective alternative compared to SGLPT-2i and GLP-1RA.

Cost-Effectiveness of Dipeptidylpeptidase-4 Inhibitors Added to Metformin in Patients With Type 2 Diabetes in China.

Purpose: Dipeptidylpeptidase-4 (DPP-4) inhibitors, including linagliptin, alogliptin, saxagliptin, sitagliptin, and vildagliptin, are used for the treatment of type 2 diabetes mellitus (T2DM) patients in China. This study assessed the economic outcomes of different DPP-4 inhibitors in patients with T2DM inadequately controlled with metformin in the Chinese context. Materials and Methods: In this study, the validated Chinese Outcomes Model for T2DM (COMT) was conducted to project economic outcomes from the perspective of Chinese healthcare service providers. Efficacy and safety, medical expenditure, and utility data were derived from the literature, which were assigned to model variables. The primary outputs of the model included the lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analysis was conducted to assess the potential uncertainties of parameters. Results: Of the five competing strategies, alogliptin 25 mg strategy yielded the most significant health outcome, which associated with improvements in discounted QALY of 0.007, 0.014, 0.011, and 0.022 versus linagliptin 5 mg, saxagliptin 5 mg, sitagliptin 100 mg and vildagliptin50 mg, respectively. The sitagliptin 100 mg strategy was the cheapest option. The ICER of alogliptin 25 mg against sitagliptin 100 mg strategy was $6,952 per additional QALY gained, and the rest of the strategies were dominated or extended dominated. The most influential parameters were the cost of DPP-4 inhibitors and their treatment efficacy. Conclusions: These results suggested that alogliptin was a preferred treatment option compared with other DPP-4 inhibitors for Chinese patients whose T2DM are inadequately controlled on metformin monotherapy.

Cost and clinical impact of a nonmedical DPP-4 inhibitor switch in patients with diabetes.

BACKGROUND: Nonmedical formulary switches (NMFS) routinely occur in managed health care plans and involve changing preferred medications for reasons outside of clinical considerations. The cost implications of NMFS are infrequently published and the clinical outcomes rarely assessed. OBJECTIVE: To assess the real-world clinical and cost implications of an NMFS involving sitagliptin and linagliptin. METHODS: An NMFS was made to the Geisinger Health Plan (GHP) commercial, health care reform, and Medicaid formularies on February 1, 2018, involving a change in preferred medication from sitagliptin to linagliptin. Claims data from GHP and clinical information from electronic health records of the Geisinger Health System were used to evaluate the cost and clinical impact of this change. Patients aged 18 years or older who were continuously enrolled in a GHP commercial, health care reform, or Medicaid plan throughout the entire study period and had at least 1 fill for sitagliptin during the preswitch phase were included in the study. We investigated the differences in various clinical and economic outcomes from pre- to postswitch among those who switched and remained adherent to the new preferred therapy throughout the 12-month postperiod ("linagliptin switch" group) and patients who did not ("other switch" group). Clinical outcomes included all-cause hospitalization, diabetes-related hospitalization, and glycosylated hemoglobin (HbA1c), while economic measures included changes in per member per month (PMPM) spending. The negative binomial regression model was used to estimate utilization counts. A generalized linear model with a log link and gamma distribution was used to analyze cost data. RESULTS: 1,203 patients met the inclusion criteria. Of these, 501 (41.6%) individuals switched to and remained at least 80% adherent to linagliptin in the postperiod, while 702 (58.4%) did not. No difference between groups was found when comparing the pre- to postswitch change in all-cause hospitalization (incidence rate ratio (IRR) = 1.46, 95% CI = 0.66-3.23, P = 0.3436) or diabetes-related hospitalization (IRR = 1.39, 95% CI = 0.62-3.10, P = 0.4203). Additionally, no difference was found between groups regarding the change in HbA1c 12-month postswitch compared with baseline (difference between groups = -0.10%, 95% CI = -0.39%-0.19%, P = 0.4962). Total PMPM spending was 43% higher in the other switch group compared with the linagliptin switch group (IRR = 1.43, 95% CI = 1.25-1.63, P < 0.0001). This trend was driven by 92% higher medical PMPM spending in the other switch group compared with the linagliptin switch group (IRR = 1.92, 95% CI = 1.58-2.33, P < 0.0001) but was offset by 12% lower pharmacy PMPM spending in the other switch group (IRR = 0.88, 95% CI = 0.82-0.95, P = 0.0009). CONCLUSIONS: An NMFS from sitagliptin to linagliptin resulted in overall health plan savings with no significant changes in health outcomes. DISCLOSURES: Funding for this study was provided by Geisinger Health System, which had no role in the study outside of a final review of the submitted manuscript. Johns and Gionfriddo are Geisinger employees. The authors report no financial conflicts of interest.

Health care utilization and costs associated with switching from DPP-4i to GLP-1RA or SGLT2i: an observational cohort study.

BACKGROUND: Because of improved clinical outcomes, recent American Diabetes Association guidelines recommend the use of newer antidiabetic agents-glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i)-by those with cardiovascular disease. It is unclear, however, how switching to these newer agents affects health care utilization and costs. OBJECTIVE: To compare health care utilization and costs between users of dipeptidyl peptidase-4 inhibitors (DPP-4i) who switch to GLP-1RA or SGLT2i and nonswitchers. METHODS: We used claims data from a large pharmacy benefit manager. Patients included were commercially insured adults with type 2 diabetes and a prescription claim for DPP-4i in 2016 or 2017. Using propensity score methods, we matched patients who switched to SGLT2i or GLP-1RA with those who remained on DPP-4i. Among matched samples, we conducted multivariable negative binomial regression to examine differences in the incidence of inpatient and emergency room (ER) visits and generalized linear regression to examine differences in health care costs. RESULTS: Among 47,953 patients who used DPP-4i in 2016 and 2017, 507 switched to SGLT2i and 808 switched to GLP-1RA. Propensity score matching of 1:6 resulted in 3,042 nonswitchers/507 switchers for the SGLT2i cohort and 4,848 nonswitchers/808 switchers for the GLP-1RA cohort. Switchers to SGLT2i experienced a 39% reduction (incidence rate ratio [IRR] = 0.61, 95% CI = 0.38-0.96), and GLP-1RA switchers experienced a 29% reduction (IRR = 0.71, 95% CI = 0.52-0.97) in inpatient hospitalizations. ER visit rates did not differ significantly between switchers and nonswitchers. Switchers to SGLT2i did not have statistically significant differences in medical or pharmacy costs compared with DPP-4i users, while switchers to GLP-1RA had significantly higher total pharmacy costs (adjusted difference of $2,453.10, 95% CI = $1,837.20-$3,069.00). CONCLUSIONS: Switching from DPP-4i to GLP-1RA or SGLT2i was associated with fewer hospitalizations; however, higher pharmacy costs may outweigh savings from reduced hospitalizations, especially for GLP-1RAs. As newer diabetes guidelines steer specific populations to these drug classes, it is important to optimize drug pricing to realize their true value. DISCLOSURES: No outside funding supported this study. Neilson, Good, Swart, and Huang are employees of UPMC Center for Value-Based Pharmacy Initiatives and High-Value Care. Parekh reports employment at UPMC until July 2019. Munshi and Henderson are employed by Express Scripts. Newman has no disclosures to report.

Penetration rates of new pharmaceutical products in Europe: A comparative study of several classes recently launched in type-2 diabetes.

BACKGROUND: Different countries have their own systems for evaluating new medicines, and they make decisions as to when and how each new medicine is adopted. PURPOSE: To compare the rate of uptake of new diabetes medicines (dipeptidyl peptidase-4 inhibitors [DPP-4Is], glucagon-like peptide-1 receptor agonists [GLP1-RAs], and sodium-glucose co-transporter-2 inhibitors [SGLT2Is]) in the five most populated European countries. METHODS: The monthly volume of sales of antidiabetic drugs was extracted for each country from the IQVIA™ MIDAS® database for the period 2007 to 2016 and the defined daily doses (DDDs) were calculated. For each new drug, market shares were expressed as a percentage of the total market of non-insulin antidiabetic agents. RESULTS: Sharp differences were observed between the countries. Overall, the highest and fastest rates of uptake were seen for Germany and Spain, compared to lower rates for the UK and Italy. This was especially marked for DPP-4Is, where the market share reached over 30% of non-insulin antidiabetic drugs in Germany and Spain, compared to around 10% in the UK and Italy. In France, there was an initial rapid uptake, which stabilized at around 20% after three years. Rates of uptake were lower for the other drugs, with the GLP1-RAs reaching a market share of 2.5-4.5% in Germany, Spain and France, compared to less than 2.5% in the UK and Italy. The SGLT2Is reached a market share of 5-8% in Spain and Germany, compared to less than 4% in the UK and Italy, and they were not launched at all in France in March 2020. CONCLUSION: The differences in the uptake of new antidiabetic drugs may reflect different methods for assessing and introducing new medicines, as well as cultural factors. The uptake of the new medicines would appear to be more cautious in the UK and Italy, perhaps due to concerns about cost-effectiveness, whereas in Germany and Spain, and possibly also France, a new medicine's potential benefits may be prioritized.

The cost-effectiveness of dapagliflozin compared to DPP-4 inhibitors in the treatment of type 2 diabetes mellitus in the Netherlands.

AIM: When glycaemic control for people with type 2 diabetes is not achieved with metformin and sulfonylurea alone, adding another oral anti-diabetes drug, such as a sodium-glucose co-transporter 2 (SGLT2) or dipeptidyl peptidase-4 (DPP-4) inhibitor, is an alternative to starting insulin. The aim of this study is to determine the cost-effectiveness of dapagliflozin (an SGLT2 inhibitor) compared with DPP-4 inhibitors when added to metformin and sulfonylurea in people with type 2 diabetes in the Netherlands. METHODS: A cost-utility analysis is performed using the Cardiff diabetes model, a fixed-time increment stochastic simulation model informed by 'United Kingdom Prospective Diabetes Study 68' risk equations. The base-case analysis uses a 40-year time horizon, a Dutch societal perspective and differential discounting (4% for costs, 1.5% for effects). Inputs are obtained from the literature and Dutch price lists. Univariate and probabilistic sensitivity analysis are performed. RESULTS: Dapagliflozin is dominant compared with DPP-4 inhibitors, resulting in a €990 cost saving and a 0.28 quality-adjusted life year gain over 40 years. Cost savings are associated mainly with treatment costs and a reduced incidence of micro- and macrovascular complications, among others nephropathy, myocardial infarction and stroke. Results are robust to changes in input parameters. CONCLUSIONS: Dapagliflozin is a cost-saving alternative to DPP-4 inhibitors when added to metformin and sulfonylurea. The incidence of micro- and macrovascular complications is lower for people treated with dapagliflozin. Uncertainty around this outcome is low.

Decreased Antihyperglycemic Drug Use Driven by High Out-of-Pocket Costs Despite Medicare Coverage Gap Closure.

OBJECTIVE: Using the 2016 Medicare Part D coverage gap as an example, we explored effects of increased out-of-pocket costs on adherence to branded dipeptidyl peptidase 4 inhibitors (DPP-4i) in patients without financial subsidies relative to subsidized patients who do not experience increased spending during the gap. We also explored seasonality of reinitiation, because discontinuers may be more likely to reinitiate in January when benefits reset. RESEARCH DESIGN AND METHODS: We identified DPP-4i or sulfonylurea initiators, aged ≥66 years, from a 20% sample of 2015-2016 Medicare claims. Difference-in-differences Poisson regression was used to compare adherence before and after entering the coverage gap between nonsubsidized and subsidized patients. Among discontinuers, monthly hazard ratios (HRs) for reinitiation relative to January 2016 were derived with Cox models. As a second control, we repeated analyses using sulfonylureas, generic low-cost alternatives. RESULTS: In 2016, 8,096 subsidized and 6,173 nonsubsidized DPP-4i initiators entered the coverage gap. For nonsubsidized patients, copayment in the coverage gap was 45% ($227 per DPP-4i prescription), and adherence decreased from 68.4% to 49.0% after gap entry. Accounting for adherence differences in subsidized patients, nonsubsidized patients demonstrated reduced adherence to DPP-4i (difference-in-difference: -16.9%; 95% CI -18.7%, -15.1%) but not sulfonylureas (-1.6%; 95% CI -3.4%, 0.2%). Reinitiation was lowest in the months before January (HR 0.4-0.5) among nonsubsidized DPP-4i patients, demonstrating a strong seasonal pattern. CONCLUSIONS: Increased out-of-pocket costs negatively affect adherence and reinitiation of branded antihyperglycemic drugs among patients without financial subsidies. Despite closure of the coverage gap, affordability remains a concern given increasing list prices for many drugs on Medicare and the growing use of deductibles and coinsurance by commercial health plans.

Comparison of heart failure risk and medical costs between patients with type 2 diabetes mellitus treated with dapagliflozin and dipeptidyl peptidase-4 inhibitors: a nationwide population-based cohort study.

BACKGROUND: Dapagliflozin is one of the novel glucose-lowering agents, which has recently been reported to reduce the risk of hospitalization for heart failure (hHF). The present study aimed to compare the differences between the risk of hHF after using dapagliflozin and dipeptidyl peptidase-4 inhibitors (DPP-4i) as second-line drugs for the treatment of type 2 diabetes mellitus using the latest nationwide population data in Korea. Additionally, we aimed to examine the impact of clinical outcomes on direct medical costs in the two groups. METHODS: The present population-based, retrospective cohort study was conducted using the nationwide claims data between September 01, 2014 and June 30, 2018. New users of dapagliflozin and DPP-4i were identified from the database and the differences in patients' characteristics between the two groups were analyzed using propensity score-weighted analysis. Cox proportional hazards regression analysis was used to estimate the risk of hHF. A simple model was used for the estimation of direct medical costs for 3 years. RESULTS: In total, 23,147 patients in the dapagliflozin group and 237,187 patients in the DPP-4i group were selected for the analysis. The incidence rates of hHF were 3.86 and 6.79 per 1000 person-years in the dapagliflozin and DPP-4i groups, respectively. In the entire study population, the hazard ratio for hHF in the dapagliflozin group compared to the DPP-4i group was 0.58 (95% confidence interval 0.46-0.74), with 0.55 (95% confidence interval 0.41-0.74) among patients with underlying cardiovascular disease and 0.66 (95% confidence interval 0.46-0.95) among patients without underlying cardiovascular disease. The direct medical costs were $57,787 lower in the dapagliflozin group than in the DPP-4i group for 3 years. CONCLUSIONS: This study showed that dapagliflozin lowers the risk for hHF and subsequently reduces direct medical costs compared to DPP-4i. The protective effect against hHF was more evident among patients with underlying cardiovascular disease.

Economic benefit of prescribing an adjusted renal dose of dipeptidyl peptidase IV inhibitors in type 2 diabetes patients with chronic kidney disease.

Highlights Based on nationwide insurance data in Korea, the use of dipeptidyl peptidase IV inhibitors (DPP-IVi) not requiring renal dose adjustment (NRDA DPP-IVi) is widespread in the type 2 diabetes chronic kidney disease (T2D CKD) population. Instead of prescribing NRDA DPP-IVi, the use of DPP-IVi requiring renal dose adjustment with appropriate renal dose adjustments in T2D CKD patients can achieve a considerable annual cost saving of up to 7.8%.

Budget impact analysis for dapagliflozin in type 2 diabetes in Egypt.

Introduction: Type 2 diabetes mellitus (T2DM) is a major health problem in Egypt with a high impact on morbidity, mortality, and healthcare resources. This study evaluated the budget impact and the long-term consequences of dapagliflozin versus other conventional medications, as monotherapy, from both the societal and health insurance perspectives in Egypt.Methods: A static budget impact model was developed to estimate the financial consequences of adopting dapagliflozin on the healthcare payer budget. We measured the direct medical costs of dapagliflozin (new scenario) as monotherapy, compared to metformin, insulin, sulphonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinedione, and repaglinide (old scenarios) over a time horizon of 3 years. Myocardial infarction (MI), ischemic stroke, hospitalization for heart failure (HHF), and initiation of renal replacement therapy (RRT) rates were captured from DECLARE TIMI 58 trial. One-way sensitivity analyses were conducted.Results: The budget impact model estimated 2,053,908 patients eligible for treatment with dapagliflozin from a societal perspective and 1,207,698 patients from the health insurance (HI) perspective. The new scenario allows for an initial savings of EGP121 million in the first year, which increased to EGP243 and EGP365 million in the second and third years, respectively. The total cumulative savings from a societal perspective were estimated at EGP731 million. Dapagliflozin allows for savings of EGP71, EGP143, and EGP215 million in the first, second and third years respectively, from the HI perspective, with total cumulative savings of EGP430 million over the 3 years.Conclusion: Treating T2DM patients using dapagliflozin instead of conventional medications, maximizes patients' benefits and decreases total costs due to drug cost offsets from fewer cardiovascular and renal events. The adoption of dapagliflozin is a budget-saving treatment option, resulting in substantial population-level health gains due to reduced event rate and cost savings from the perspective of the national healthcare system.

Cost-effectiveness of diabetes treatment sequences to inform step therapy policies.

OBJECTIVES: Cost-effectiveness estimates are useful to a health plan when they are specific to a utilization management policy question. To help inform a step therapy policy decision, this study assessed the 3-year cost-effectiveness of adding a sodium-glucose cotransporter 2 (SGLT2) inhibitor versus switching to a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in patients with type 2 diabetes who are on metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor from both private and public payer perspectives in the United States. STUDY DESIGN: Cost-effectiveness analysis. METHODS: A decision-analytic model was built incorporating goal glycated hemoglobin (A1C) achievement as the effectiveness measure, as well as adverse effect and discontinuation rates from clinical trial data. One-way, scenario, and probabilistic sensitivity analyses were performed. RESULTS: In a cohort of 1000 patients, adding an SGLT2 inhibitor led to $3.9 million more in spending and 93 more patients reaching goal A1C compared with switching from a DPP-4 inhibitor to a GLP-1 RA. This resulted in an incremental cost-effectiveness ratio (ICER) of $42,125 per patient to achieve goal A1C from the private payer perspective. Using a public payer perspective led to an ICER of $103,829. These results were most sensitive to changes in drug costs and the proportion of patients achieving A1C goal or discontinuing. CONCLUSIONS: Assuming a $50,000 willingness-to-pay threshold, adding an SGLT2 inhibitor was cost-effective compared with switching from a DPP-4 inhibitor to a GLP-1 RA from a private payer perspective but not from a public payer perspective. This study highlights how differences in payer reimbursement rates for medications can lead to contrasting results.

Cost Utility of Sodium-Glucose Cotransporter 2 Inhibitors in the Treatment of Metformin Monotherapy Failed Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) and associated ailments are leading economic burdens to society. Sodium glucose cotransporter-2 (SGLT2) inhibitors are recent antidiabetic medications with beneficial clinical efficacy. This meta-analysis was conducted to quantitatively pool the incremental net benefit of SGLT2 inhibitors in T2DM patients who failed metformin monotherapy. METHODS: Relevant economic evaluation studies of T2DM patients were identified from PubMed, Scopus, ProQuest, the Cochrane Library, and the Tufts Cost-Effective Analysis Registry until June 2018. Studies were eligible if they studied T2DM patients who failed metformin monotherapy and assessed the cost-effectiveness/utility between SGLT2 inhibitors and other treatments. Details of the study characteristics, economic model inputs, costs, and outcomes were extracted. Risk of bias was assessed using the biases in economic studies (ECOBIAS) checklist. The incremental net benefit was calculated with monetary units adjusting for purchasing power parity for 2017 US dollars. This was then pooled across studies stratified by the country's level of income using a random-effect model if heterogeneity was present and with a fixed-effect model otherwise. Heterogeneity was assessed using the Q test and I2 statistic. RESULTS: A total of 13 studies with 22 comparisons, mainly from high-income countries, were eligible. Six and 4 studies compared SGLT2 with dipeptidyl peptidase-4 inhibitors (DPP4i) and sulfonylureas, respectively. The pooled incremental net benefits (95% confidence interval) for these corresponding comparisons were $164.95 (-$534.71 to $864.61; I2 = 0%) and $3675.09 ($1656.46-$5693.71; I2 = 85.4%), respectively. These results indicate that SGLT2s were cost-effective in comparison with sulfonylureas but not DPP4i. CONCLUSION: SGLT2s were cost-effective as compared with sulfonylureas but not DPP4i. Most of the evidence was from high-income countries with few comparative drug groups, and the results might not be representative of the actual global scenario. Further studies from middle and lower economies and other comparators are still required.

Cost and Utilization Outcomes After Exclusion of Dipeptidyl Peptidase-4 Inhibitors and Other Diabetes Drug Category Changes in a Self-Funded, State Employee Managed Care Plan.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have repeatedly shown no reduction in the clinical outcomes of cardiovascular death, myocardial infarction, stroke, or all-cause mortality. Because the treatment of diabetes is generally one of the top drug categories by cost to health plans and self-funded employers, it is necessary to evaluate coverage of DPP-4 inhibitors, considering their lack of cardiovascular benefit relative to other treatment options. OBJECTIVE: To describe the cost and utilization outcomes of drugs used to treat diabetes after exclusion of DPP-4 inhibitors in a self-funded managed care plan. METHODS: This study was a retrospective, descriptive analysis of the cost and utilization outcomes after exclusion of DPP-4 inhibitors. Pharmacy claims data and plan membership were analyzed 6 months before DPP-4 inhibitor exclusion (preperiod: December 1, 2016-May 31, 2017) and 6 months after DPP-4 inhibitor coverage ended for all users (postperiod: September 1, 2017-February 28, 2018). The allowed amount, which is not influenced by overlapping plan copay changes, and utilization per member per month (PMPM) were used to estimate the effect of the DPP-4 inhibitor benefit exclusion on plan costs for the antidiabetic class. RESULTS: From preperiod to postperiod, all DPP-4 inhibitor products decreased in utilization by 3.02 claims per 1,000 members per month (PTMPM). Glucagon-like peptide-1 receptor agonists, insulins, sodium-glucose cotransporter-2 inhibitors, and thiazolidinedione claims increased by 0.72, 0.43, 0.30, and 0.48 claims PTMPM, respectively, but there was an absolute decrease of 1.35 claims for antidiabetic medications per 1,000 plan members. However, the days supplied PMPM increased from 2.55 to 2.61 (2.3%) days. Allowed amount PMPM increased by $0.27 from $12.19 in the preperiod to $12.31 in the postperiod (2.2%). However, it is estimated that drug cost inflation accounted for over half of the PMPM increase in allowed costs. CONCLUSIONS: The observed increase in the allowed amount PMPM was attributable in similar amounts by an increase in utilization of medications with higher cost per day supplied and higher drug prices. Future research will evaluate patient-level effects of this benefit change in terms of antidiabetic medication utilization and outcomes. DISCLOSURES: No outside funding supported this study. Davis, Bemberg, and Johnson currently work for or previously worked for the UAMS Evidence-Based Prescription Drug Program, which advises the Employee Benefits Division (EBD) on pharmacy benefit management. The EBD did not provide any additional funding for this study. McAdam-Marx reports grants from AstraZeneca and Sanofi Aventis outside the submitted work. The other authors have no other relevant information to disclose.

Cost-effectiveness of DPP-4 inhibitor and SGLT2 inhibitor combination therapy for type 2 diabetes.

OBJECTIVES: Maintaining glycemic control limits costly health risks in patients with type 2 diabetes (T2D), but accomplishing this may require individualized strategies. Generic medications (eg, sulfonylureas [SU], insulin) are common in T2D management due to their efficacy and costs; however, relatively new drug classes (eg, dipeptidyl peptidase 4 [DPP-4] inhibitors, sodium-glucose cotransporter 2 [SGLT2] inhibitors) have demonstrated clinical benefits in combination therapy. The objective of this study was to evaluate the long-term cost-effectiveness of a strategy involving branded combination therapy with DPP-4 inhibitors and SGLT2 inhibitors (pathway 1) compared with a generic alternative with SU and insulin (pathway 2) on a background of metformin. STUDY DESIGN: Cost-effectiveness analysis using the validated IQVIA CORE Diabetes Model from the US payer perspective. METHODS: Cost-effectiveness analysis. Lifetime clinical and economic outcomes (discounted 3%/year) were modeled for a T2D cohort failing to achieve glycemic goal on metformin monotherapy. Patient baseline data and treatment effects reflect results of clinical trials. Direct medical cost inputs are from multiple published sources. Scenario analyses on key intervention effects and assumptions tested robustness of results. RESULTS: Pathway 1 had higher direct medical costs compared with pathway 2, yet also increased total quality-adjusted life-years (QALYs) by 0.24. Increased costs were partially offset by a reduction in diabetes-related complications and delayed insulin initiation. The incremental cost-effectiveness ratio (ICER) for pathway 1 is favorable at $64,784/QALY. Scenario analyses showed limited impact; nearly all ICERs were less than $100,000/QALY. CONCLUSIONS: In the United States, sequential addition of SGLT2 inhibitors to DPP-4 inhibitors may be considered cost-effective compared with traditional treatment with generic medications for patients who fail to achieve glycemic goal on metformin.

Cost Effectiveness of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists, and Dipeptidyl Peptidase-4 (DPP-4) Inhibitors: A Systematic Review.

OBJECTIVE: This study aimed to systematically review cost-effectiveness studies of newer antidiabetic medications. METHODS: The PubMed/MEDLINE, EMBASE, CINAHL Plus, Cochrane Library-NHS Economic Evaluation Database (Wiley), Cochrane Library-Health Technology Assessment Database (Wiley), Cochrane Library-Database of Abstracts of Reviews of Effects (Wiley), and the Cost-Effectiveness Analysis Registry databases (from 1 January 2000 to 1 June 2018) were searched. The search strategies included the Medical Subject Heading (MeSH) term 'economics', and the MeSH entry terms 'cost', 'cost effectiveness', 'value', and 'cost utility', as well as all names for GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors. Inclusion criteria included (1) cost-effectiveness studies of the newer antidiabetic medications, including sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors; and (2) full-text publications in English. Two reviewers independently screened the titles, abstracts, and full-text articles to select studies for data extraction. Discrepancies were resolved by discussion and consensus. The quality of reporting cost-effectiveness analyses was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guideline. RESULTS: Among 85 studies selected, 82 clearly stated the types of diabetes model used (e.g. CORE model), and 70 studied used validated diabetes models. Seventy-four (87%) studies were funded by pharmaceutical companies, and 72 (85%) studies were conducted from a payer's perspective. Seventy-six (89%) studies presented were of good quality (20-24 CHEERS items), and nine were of moderate quality (14-19 items). Thirty studies compared newer antidiabetic medications with insulin, 3 studies compared newer antidiabetic medications with thiazolidinediones (TZDs), 15 studies compared newer antidiabetic medications with sulfonylureas, 40 studies compared new antidiabetic medications with alternative newer antidiabetic medication, and 9 studies compared other antidiabetic agents that were not included above. Newer antidiabetic medications were reported to be cost-effective in 26 of 30 (87%) studies compared with insulin, and 13 of 15 (87%) studies compared with sulfonylureas. CONCLUSIONS: Most economic evaluations of antidiabetic medications have good reporting quality and use validated diabetes models. The newer antidiabetic medications in most of the reviewed studies were found to be cost effective, compared with insulin, TZDs, and sulfonylureas.

Penetration of new antidiabetic medications in East Asian countries and the United States: A cross-national comparative study.

BACKGROUND: The number of patients with diabetes is increasing particularly in Asia-Pacific region. Many of them are treated with antidiabetics. As the basis of the studies on the benefit and harm of antidiabetic drugs in the region, the information on patterns of market penetration of new classes of antidiabetic medications is important in providing context for subsequent research and analyzing and interpreting results. METHODS: We compared penetration patterns of dipeptidyl peptidase-4 (DPP-4) inhibitors in Taiwan, Hong Kong, Japan, and the United States. We used the Taiwan National Health Insurance Research Database, a random sample of the Hong Kong Clinical Data Analysis and Reporting System, the Japan Medical Data Center database, and a 5% random sample of the US Medicare database converted to the Observational Medical Outcomes Partnership's Common Data Model to identify new users of oral antidiabetic medications. We standardized prevalence and incidence rates of medication use by age and sex to those in the 2010 Taiwanese population. We compared age, sex, comorbid conditions, and concurrent medications between new users of DPP-4 inhibitors and biguanides. RESULTS: Use of DPP-4 inhibitors 1 year after market entry was highest in Japan and lowest in Hong Kong. New users had more heart failure, hyperlipidemia, and renal failure than biguanide users in Taiwan, Hong Kong, and the United States while the proportions were similar in Japan. In a country with low penetration of DPP-4 inhibitors (eg, Hong Kong), users had diabetes with multiple comorbid conditions compared with biguanidine users. In a country with high penetration (eg, Japan), the proportion of users with comorbid conditions was similar to that of biguanide users. CONCLUSIONS: We observed a marked difference of the penetration patterns of newly marketed antidiabetics in different countries in Asia. Those results will provide the basic information useful in the future studies.

Switching from sitagliptin to liraglutide to manage patients with type 2 diabetes in the UK: A long-term cost-effectiveness analysis.

AIMS: The recent LIRA-SWITCH trial showed that switching from sitagliptin 100 mg to liraglutide 1.8 mg led to statistically significant and clinically relevant improvements in glycated haemoglobin (HbA1C) and body mass index (BMI). Based on these findings, the aim of the present study was to assess the long-term cost-effectiveness of switching from sitagliptin to liraglutide in patients with type 2 diabetes in the UK. MATERIALS AND METHODS: The IQVIA CORE Diabetes Model Version 8.5+ was used to project costs and clinical outcomes over patients' lifetimes. Baseline cohort characteristics and treatment effects were derived from the LIRA-SWITCH trial. Future costs and clinical benefits were discounted at 3.5% annually. Costs were accounted in pounds sterling (GBP) and expressed in 2016 values. One-way and probabilistic sensitivity analyses were performed. RESULTS: Model projections showed improved quality-adjusted life expectancy for patients with poorly controlled HbA1c upon switching from sitagliptin to liraglutide, compared with continuing sitagliptin treatment (9.18 vs 9.02 quality-adjusted life years [QALYs]). Treatment switching was associated with increased overall costs (GBP 24737 vs GBP 22362). Higher pharmacy costs were partially offset by reduced diabetes-related complication costs in patients who switched to liraglutide. Switching to liraglutide was associated with an incremental cost-effectiveness ratio of GBP 15423 per QALY gained vs continuing with sitagliptin treatment. CONCLUSIONS: Switching from sitagliptin 100 mg to liraglutide 1.8 mg in patients with poor glycaemic control was projected to improve clinical outcomes and is likely to be considered cost-effective in the UK setting and, therefore, a good use of limited NHS resources.

Cost-effectiveness analysis of metformin+dipeptidyl peptidase-4 inhibitors compared to metformin+sulfonylureas for treatment of type 2 diabetes.

BACKGROUND: Patients with type 2 diabetes (T2D) typically use several drug treatments during their lifetime. There is a debate about the best second-line therapy after metformin monotherapy failure due to the increasing number of available antidiabetic drugs and the lack of comparative clinical trials of secondary treatment regimens. While prior research compared the cost-effectiveness of two alternative drugs, the literature assessing T2D treatment pathways is scarce. The purpose of this study was to evaluate the long-term cost-effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4i) compared to sulfonylureas (SU) as second-line therapy in combination with metformin in patients with T2D. METHODS: A Markov model was developed with four health states, 1 year cycle, and a 25-year time horizon. Clinical and cost data were collected from previous studies and other readily available secondary data sources. The incremental cost-effectiveness ratio (ICER) was estimated from the US third party payer perspective. Both, costs and outcomes, were discounted at a 3% annual discount rate. One way and probabilistic sensitivity analyses were performed to evaluate the impact of uncertainty on the base-case results. RESULTS: The discounted incremental cost of metformin+DPP-4i compared to metformin+SU was $11,849 and the incremental life-years gained were 0.61, resulting in an ICER of $19,420 per life-year gained for patients in the metformin+DPP-4i treatment pathway. The ICER estimated in the probabilistic sensitivity analysis was $19,980 per life-year gained. Sensitivity analyses showed that the results of the study were not sensitive to changes in the parameters used in base-case. CONCLUSIONS: The metformin+DPP-4i treatment pathway was cost-effective compared to metformin+SU as a long-term second-line therapy in the treatment of T2D from the US health care payer perspective. Study findings have the potential to provide clinicians and third party payers valuable evidence for the prescription and utilization of cost-effective second-line therapy after metformin monotherapy failure in the treatment of T2D.

Impact of formulary restrictions on medication use and costs.

OBJECTIVES: To evaluate the effects of formulary restrictions on utilization and costs of oral hypoglycemic agents (OHAs), statins, and renin-angiotensin system (RAS) antagonists among low-income subsidy (LIS) recipients in Medicare Part D plans. STUDY DESIGN: We analyzed a 5% sample of 2012 Medicare data from the Chronic Conditions Data Warehouse together with a customized dataset capturing beneficiaries' histories of plan assignment. METHODS: We constructed 3 nonexclusive study cohorts comprising of users of OHAs, statins, and RAS antagonists. Eligible study subjects were LIS recipients randomized to benchmark plans. Formulary restrictions of interest were noncoverage, prior authorization, and step therapy. Study outcomes included generic dispensing rate (GDR), mean cost per prescription fill, and medication adherence based on proportion of days covered (PDC). Random intercept regression models were performed to estimate the effects of formulary restrictions on the study outcomes by drug class. RESULTS: After covariate adjustment, beneficiaries who were subject to formulary restrictions on brand name pioglitazone and single-source brand name dipeptidyl peptidase-4 inhibitors (saxagliptin, sitagliptin, and sitagliptin-metformin) had a GDR 3 percentage points higher and a cost per prescription fill $10.8 less, but similar PDC compared with those who faced no restrictions. Restricting access to brand name atorvastatin and single-source brand name statins (rosuvastatin and ezetimibe-simvastatin) was associated with a GDR 14.9 percentage points higher and a cost per prescription fill $29.6 less, but with no impact on PDC. Restricting use of single-source brand name RAS antagonists (olmesartan, valsartan, and valsartan-hydrochlorothiazide) was associated with a GDR 15.0 percentage points higher, a cost per prescription fill $27.2 less, and a PDC 1.3 percentage points lower. CONCLUSIONS: Placing formulary restrictions on brand name drugs shifts utilization toward generic drugs, lowers the overall cost per prescription fill, and has minimal impact on overall adherence for OHAs, statins, and RAS antagonists among LIS recipients.