title: Adherence, Persistence, and Health Care Costs for Patients Receiving Dipeptidyl Peptidase-4 Inhibitors.
abstract: BACKGROUND
  The dipeptidyl peptidase-4 (DPP-4) inhibitors are among the newer, yet more established, classes of diabetes medications.
  
  
  OBJECTIVE
  To compare adherence, persistence, and health care costs among patients taking DPP-4 inhibitors.
  
  
  METHODS
  Claims were extracted from Humana Medicare Advantage Prescription Drug (MAPD) or commercial plans for patients aged > 18 years with ≥ 1 prescription filled for a DPP-4 inhibitor between July 1, 2011, and March 31, 2013. The first prescription claim for a DPP-4 inhibitor established the index date and index medication; 12-month pre-index and post-index data were analyzed. The Diabetes Complications Severity Index (DCSI) was used to assess a level of baseline diabetes-related comorbidities. Adherence (proportion of days covered [PDC] ≥ 80%) and persistence (< 31-day gap) measures were compared before and after, adjusting for DCSI, pre-index insulin, age, and gender. Post-index costs (in 2013 U.S. dollars) were compared using general linear modeling (GLM) to adjust for pre-index costs, DCSI, pre-index insulin, age, and gender.
  
  
  RESULTS
  Based on study criteria, 22,860 patients with MAPD coverage (17,292 sitagliptin, 4,282 saxagliptin, and 1,286 linagliptin) and 3,229 patients with commercial coverage (2,368 sitagliptin, 643 saxagliptin, and 218 linagliptin) were included. For MAPD patients, the mean age was 70-72 years, and females represented 50%-52% of patients. For commercial patients, mean age was 55-56 years, and females represented 44% of patients. Clinical indicators for patients on linagliptin showed a higher comorbidity level than sitagliptin or saxagliptin cohorts (MAPD DCSI 3.0 vs 2.4 and 2.2, P < 0.001; commercial DCSI 1.2 vs. 0.9 and 0.9, P < 0.001); a higher use of pre-index insulin (MAPD 22% vs. 15% and 14%, P < 0.001; commercial 18% vs. 11% and 10%, P = 0.003); and higher mean pre-index costs (MAPD $14,448 vs. $11,818 and $10,399, P < 0.001; commercial $13,868 vs. $9,357 and $8,223, P = 0.016). For the MAPD cohort, the unadjusted PDC was lower for linagliptin patients (67%) compared with saxagliptin (72%) or sitagliptin (72%) patients (P < 0.001). Significant differences were still seen when adjusted for covariates. Linagliptin patients were more likely to be nonpersistent (73%) than those on saxagliptin (65%) or sitagliptin (67%; P < 0.01 for adjusted and unadjusted comparisons). For the commercial population, there were no significant differences in mean PDC between the 3 groups (linagliptin 70%, saxagliptin 72%, and sitagliptin 74%; P = 0.096). Dichotomized comparisons of nonpersistence were significantly different (linagliptin 65%, saxagliptin 62%, and sitagliptin 57%; P = 0.010), although upon adjustment using a Cox proportional hazard model, no significant differences were found. When controlling for other factors, post-index adjusted health care costs were similar between the medication cohorts (MAPD: sitagliptin = $13,913, saxagliptin = $13,651, and linagliptin = $13,859; commercial: sitagliptin = $11,677, saxagliptin = $12,059, and linagliptin = $11,163; all P > 0.25).
  
  
  CONCLUSIONS
  For MAPD and commercial populations, baseline patient demographics were similar between the 3 DPP-4 inhibitor groups, but the linagliptin group may have had more complex patients (higher pre-index costs, higher DCSI, and more use of insulin). For the MAPD population, patients on linagliptin were less adherent and persistent than patients taking sitagliptin or saxagliptin for all unadjusted and adjusted comparisons. For the commercial population, which was notably smaller, these differences were in the same direction, but not all were statistically significant. When controlling for baseline factors, 12-month post-index direct medical health care costs were similar between index DPP-4 inhibitors.
  
  
  BACKGROUND
  No external funding was provided for this research. The project was done as part of internal work by Humana employees. Rascati received no compensation. None of the authors have any financial disclosures or conflicts of interests to report. Worley and Everhart are employees of Comprehensive Health Insights, a subsidiary of Humana, and Meah is an employee of Humana. Discussion of the adherence and persistence data was presented as a poster at the Academy of Managed Care Pharmacy Nexus Conference, October 2015. Cost data were presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research 18th Annual European Congress, November 2015. Study concept and design were contributed by Rascati, Worley, and Meah, along with Everhart. Rascati took the lead in data collection, assisted by Meah, and data interpretation was performed by all the authors. The manuscript was written primarily by Rascati, along with Worley, Everhart, and Meah, and revised by Rascati, Everhart, and Worley, with assistance from Meah.
authors.affiliation: 1 The University of Texas College of Pharmacy at Austin.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Rascati
authors.affiliation: 2 Comprehensive Health Insights, Humana, Louisville, Kentucky.
authors.forename: Karen
authors.initials: K
authors.lastname: Worley
authors.affiliation: 3 Humana, Louisville, Kentucky.
authors.forename: Yunus
authors.initials: Y
authors.lastname: Meah
authors.affiliation: 2 Comprehensive Health Insights, Humana, Louisville, Kentucky.
authors.forename: Damian
authors.initials: D
authors.lastname: Everhart
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000191:economics; D004151:Dipeptides / Q000191:economics / Q000627:therapeutic use; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000191:economics* / Q000627:therapeutic use*; D005260:Female; D017048:Health Care Costs / Q000706:statistics & numerical data*; D006801:Humans; D007004:Hypoglycemic Agents / Q000191:economics* / Q000627:therapeutic use*; D007328:Insulin / Q000191:economics / Q000627:therapeutic use; D000069476:Linagliptin / Q000191:economics / Q000627:therapeutic use; D008297:Male; D008329:Managed Care Programs / Q000191:economics*; D008875:Middle Aged; D000068900:Sitagliptin Phosphate / Q000191:economics / Q000627:therapeutic use; D016903:Drug Monitoring
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D000069476:Linagliptin; C502994:saxagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate