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.

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.

Cost-effectiveness of vildagliptin for people with type 2 diabetes mellitus in Brazil; findings and implications.

INTRODUCTION: Vildagliptin is an inhibitor of the enzyme dipeptidyl peptidase 4, indicated for the treatment of type 2 diabetes mellitus, combined or not with metformin. This study aims to evaluate the cost-effectiveness of vildagliptin in the Brazilian context. Areas covered: Using MEDLINE, Cochrane Library, Lilacs and CRD, six studies were selected for the economic models. This study utilised cost data in the Brazilian health system to provide the context. Expert commentary: Type 2 diabetes mellitus is an epidemic disease and represents a challenge for all health care systems. Although guidelines clearly define first-line treatment, there are several other promising treatments. Vildagliptin is one of them, resulting in a mean lifetime increase of 0.31 years compared to metformin alone and 1.19 more life years compared to other metformin combinations. Considering observational data, life years with dual vildagliptin-containing treatments were 0.37 more compared to other dual treatments. However, its high cost versus generic metformin and its unclear safety profile weakens its subsequent cost-effectiveness. Consequently, the incorporation of vildagliptin or its combination with metformin is currently not recommended for the Brazilian Health Care System. This may change as more data becomes available.

[Combination therapy of metformin vs dipeptidulpeptidase inhibitors and sulfonylureas in type 2 diabetes: clinical and economic impact]. / Combinación de metformina frente a inhibidores de la dipeptidilpeptidasa y sulfonilureas en el tratamiento de la diabetes tipo 2: impacto clínico y económico.

OBJECTIVES: Determine the clinical repurcussions of adherence, metabolic control, hypoglycemia and cardiovascular events (CVE) and economics (resources and costs) in the combination therapy of metformin vs DPP-4 (dipeptidyl peptidase-4) inhibitors and sulfonylureas in patients with type 2 diabetes. Materials and methods. Observational-multicenter and retrospective design. We evaluated patients ≥ 30 years of age in treatment with metformin and who started a second oral antidiabetic treatment during 2008-2009. 2 study groups were established: a) metformin + DPP-4 inhibitors, and b) metformin + sulfonylurea. MAIN MEASURES: comorbidity, metabolic control (HbA1c <7%), compliance and complications (hypoglycemia, CVE). Follow up was conducted over two years. The cost model differentiated between direct healthcare costs (primary/ specialty care), and indirect costs (labor productivity). STATISTICAL ANALYSIS: logistic regression and ANCOVA models. Results. 1,405 patients were recruited (average age 67.1 years old; 56.2% male). 37.0% started a second treatment with DPP-4 inhibitors, and 63.0% with sulfonylureas. After two years of follow up, patients treated with DPP-4 inhibitors showed greater treatment adherence (70.3% vs. 60.6%; p <0.001); better metabolic control (64.3% vs. 60.6%; p<0.001), and a lower proportion of hypoglycemia (13.9% vs. 40.4%; p <0.001, respectively). The average/unit of adjusted total costs was € 2,341 vs. € 2,512; p = 0.038. CVE and renal failure rates were 3.7% vs. 6.4%; p = 0.027. Vildagliptin was the most used drug among DPP-4 inhibitors. Conclusions. Sulfonylureas were the most used drug for diabetes treatment. Patients treated with DPP-4 inhibitors had higher adherence and control of diabetes, with lower rates of hypoglycemia and CVE, resulting in lower healthcare costs.

Evaluación económica del tratamiento de diabetes tipo 2 con saxagliptina en Colombia / Economic evaluation of type 2 diabetes treatment with saxagliptin in Colombia

Objetivo: Determinar la relación costo efectividad incremental del agregado de saxagliptina o sulfonilureas en Colombia a personas con DMT2 que no logran alcanzar metas glucémicas con metformina, durante un período máximo de 20 años. Metodología: Se realizó un estudio de costo efectividad, utilizando un modelo de simulación de eventos discretos con incremento de tiempo fijo (Diabetes Cardiff Model). Las características de la cohorte de pacientes y el perfil de eficacia para cada tratamiento se obtuvieron de la literatura. El costo de los medicamentos se obtuvo de SISMED y Farmaprecios. Los costos de los eventos macro y microvasculares se basaron en el POS, Manual Tarifario SOAT y consulta con experto local. La tasa de descuento en costos y beneficios fue 3,5 por ciento. Resultados: En el grupo tratado con saxagliptina registramos menos eventos fatales y no fatales y menos episodios de hipoglucemia. En ambas estrategias los mayores costos correspondieron a los medicamentos, seguidos por los asociados al tratamiento del infarto de miocardio. El costo incremental de la terapia con saxagliptina fue de US$ 555.552 a 20 años. El tratamiento con saxagliptina redundó en un mayor número de Años de Vida Ajustados por Calidad (AVAC) y Años de Vida Ganados (AVG), respecto al obtenido con sulfonilureas. El costo por AVAC fue de US$ 2.190. Los resultados de costo efectividad fueron robustos al análisis de sensibilidad. Conclusión: El agregado de saxagliptina a pacientes que no logran un control glucémico adecuado con metformina, es muy costo efectiva comparada con el agregado de sulfonilureas.

Objective: To determine in Colombia, the cost effectiveness ratio of the saxagliptin or sulphonylureas addition to patients with T2DM who fail to achieve glycemic goals with metformin, for a maximum period of 20 years. Methods: We performed a cost effectiveness analysis, using a discrete event simulation model with fixed time step (Cardiff Diabetes Model). The characteristics of the cohort of patients and efficacy profile for each treatment were obtained from the literature. The cost of medication was obtained from SISMED and Farmaprecios. The costs of macro and microvascular events were based on POS tariffs, SOAT Manual and consultation with local expert. The discount rate on costs and benefits was 3.5 percent. Results: The group treated with saxagliptin had fewer fatal and nonfatal events and fewer episodes of hypoglycemia than the one with sulfonylureas. In both strategies the higher cost corresponds to the drugs, followed by those associated with the treatment of myocardial infarction. The incremental cost of saxagliptin therapy was US$ 555.552 to 20 years. Saxagliptin treatment resulted in a greater number of quality-adjusted life year (QALYs) and life-years gained (LYG) than that obtained with sulfonylureas. The cost per QALY was US$ 2,190. Cost-effectiveness results were robust to sensitivity analysis. Conclusion: Addition of saxagliptin to patients who do not achieve adequate glycemic control with metformin, is highly cost-effective compared with the addition of sulphonylureas.