PP  Vol.5 No.4 , April 2014
Liraglutide vs Exenatide: Patient Adherence, Medication Persistence and Economic Evaluation in the Treatment of Type 2 Diabetes Mellitus
Abstract: Introduction: Liraglutide and Exenatide are used in adults who are affected by type-2 diabetes to control their blood glucose level. They are administered by the patients by subcutaneous injection, Liraglutide once a day while Exenatide twice a day. The aim of this study was to evaluate medication adherence and persistence of treatment with Liraglutide and Exenatide with a new strategy of calculation also giving economic evaluations on therapy costs for Received Daily Dose. Materials and Methods: In this retrospective study, we took into account 16 months from 1st September 2011 to 31st December 2012. Treatment adherence was quantified utilizing the ratio between RDD and Prescribed Daily Dose (PDD). Persistence is calculated into account the actual therapy days, comparing posology with supplied dose and the graph is drawn using Kaplan-Meir method. Results: The number of patients studied for Liraglutide was 114 and 220 and 58 and 60 for Exenatide respectively in 2011 and 2012. Adherence to therapy, calculated as the ratio between RDD and PDD, in 2011 was 0.93 for Exenatide and 0.87 for Liraglutide, while in 2012 it was 0.94 and 0.90 for Liraglutide and Exenatide, respectively. The cost per day of therapy (cost per RDD) for Liraglutide was €2.88 and €2.78 and for Exenatide was €2.37 and €2.48 in 2011 and 2012, respectively. Conclusion: The dosage regimen, therefore, plays an important role in improving the medication adherence.
Cite this paper: Santoleri, F. , Sorice, P. , Lasala, R. and Costantini, A. (2014) Liraglutide vs Exenatide: Patient Adherence, Medication Persistence and Economic Evaluation in the Treatment of Type 2 Diabetes Mellitus. Pharmacology & Pharmacy, 5, 332-339. doi: 10.4236/pp.2014.54040.

[1]   Maraschin, J. de F. (2012) Classification of Diabetes. Advances in Experimental Medicine and Biology, 771, 12-19.

[2]   Wild, S., Roglic, G., Green, A., Sicree, R., et al. (2004) Global Prevalence of Diabetes: Estimates for the Year 2000 and Projections for 2030. Diabetes Care, 27, 1047-1053.

[3]   D’Souza, A., Hussain, M., Howarth, F.C., et al. (2009) Pathogenesis and Pathophysiology of Accelerated Atherosclerosis in the Diabetic Heart. Molecular and Cellular Biochemistry, 331, 89-116.

[4]   Davies, M.J., Chubb, B.D., Smith, I.C., et al. (2012) Cost-Utility Analysis of Liraglutide Compared with Sulphonylurea or Sitagliptin, All as Add-On to Metformin Monotherapy in Type 2 Diabetes Mellitus. Diabetic Medicine, 29, 313-320.

[5]   Butler, A.E., Janson, J., Bonner-Weir, S., et al. (2003) Beta-Cell Deficit and Increased Beta-Cell Apoptosis in Humans with Type 2 Diabetes. Diabetes, 52, 102-110.

[6]   Karaca, M., Magnan, C. and Kargar, C. (2009) Functional Pancreatic Beta-Cell Mass: Involvement in Type 2 Diabetes and Therapeutic Intervention. Diabetes & Metabolism, 35, 77-84.

[7]   Creutzfeldt, W. and Ebert, R. (1985) New Developments in the Incretin Concept. Diabetologia, 28, 565-573.

[8]   Kim, M.H. and Lee, M.K. (2010) The Incretins and Pancreatic beta-Cells: Use of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide to Cure Type 2 Diabetes Mellitus. Korean Diabetes Journal, 34, 2-9.

[9]   Baggio, L.L. and Drucker, D.J. (2007) Biology of Incretins: GLP-1 and GIP. Gastroenterology, 132, 2131-2157.

[10]   Wideman, R.D. and Kieffer, T.J. (2004) Glucose-Dependent Insulinotropic Polypeptide as a Regulator of Beta Cell Function and Fate. Hormone and Metabolic Research, 36, 782-786.

[11]   Kieffer, T.J. and Habener, J.F. (1999) The Glucagon-Like Peptides. Endocrine Reviews, 20, 876-913.

[12]   European Medicines Agency (2010) Novo Nordisk Summary of Product Characteristics: VictozaTM.

[13]   European Medicines Agency (2010) Eli Lilly & Co Summary of Product Characteristics: ByettaTM.

[14]   Aston-Mourney, K., Hull, R.L., Zraika, S., et al. (2011) Exendin-4 Increases Islet Amyloid Deposition but Offsets the Resultant Beta-Cell Toxicity in Human Islet Amyloid Polypeptide Transgenic Mouse Islets. Diabetologia, 54, 1756-1765.

[15]   Fan, R., Kang, Z., He, L., et al. (2011) Exendin-4 Improves Blood Glucose Control in Both Young and Aging Normal Non-Diabetic Mice, Possible Contribution of Beta Cell Independent Effects. PLoS One, 6, e20443.

[16]   Degn, K.B., Juhl, C.B., Sturis, J., et al. (2004) One Week’s Treatment with the Long-Acting Glucagon-Like Peptide 1 Derivative Liraglutide (NN2211) Markedly Improves 24-h Glycemia and Alpha- and Beta-Cell Function and Reduces Endogenous Glucose Release in Patients with Type 2 Diabetes. Diabetes, 53, 1187-1194.

[17]   Iltz, J.L., Baker, D.E., Setter, S.M., et al. (2006) Exenatide: An Incretin Mimetic for the Treatment of Type 2 Diabetes Mellitus. Clinical Therapeutics, 28, 652-665.

[18]   Juhl, C.B., Hollingdal, M., Sturis, J., et al. (2002) Bedtime Administration of NN2211, a Long-Acting GLP-1 Derivative, Substantially Reduces Fasting and Postprandial Glycemia in Type 2 Diabetes. Diabetes, 51, 424-429.

[19]   Bregenholt, S., Møldrup, A., Blume, N., et al. (2005) The Long-Acting Glucagon-Like Peptide-1 Analogue, Liraglutide, Inhibits Beta-Cell Apoptosis in Vitro. Biochemical and Biophysical Research Communications, 330, 577-584.

[20]   Wajchenberg, B.L. (2007) Beta-Cell Failure in Diabetes and Preservation by Clinical Treatment. Endocrine Reviews, 28, 187-218.

[21]   Lotfy, M., Singh, J., Kalász, H., et al. (2011) Medicinal Chemistry and Applications of Incretins and DPP-4 Inhibitors in the Treatment of Type 2 Diabetes Mellitus. The Open Medicinal Chemistry Journal, 5, 82-92.

[22]   Fakhoury, W.K., Lereun, C. and Wright, D. (2010) A Meta-Analysis of Placebo-Controlled Clinical Trials Assessing the Efficacy and Safety of Incretin-Based Medications in Patients with Type 2 Diabetes. Pharmacology, 86, 44-57.

[23]   Brown, D.X. and Evans, M. (2012) Choosing between GLP-1 Receptor Agonists and DPP-4 Inhibitors: A Pharmacological Perspective. Journal of Nutrition and Metabolism, 2012, 381713.

[24]   Doggrell, S.A. (2013) Exenatide Extended-Release; Clinical Trials, Patient Preference, and Economic Considerations. Patient Preference and Adherence, 7, 35-45.

[25]   Karve, S., Cleves, M.A., Helm, M., et al. (2009) Prospective Validation of Eight Different Adherence Measures for Use with Administrative Claims Data among Patients with Schizophrenia. Value in Health, 12, 989-995.

[26]   Karve, S., Cleves, M.A., Helm, M., et al. (2008) An Empirical Basis for Standardizing Adherence Measures Derived from Administrative Claims Data among Diabetic Patients. Medical Care, 46, 1125-1133.

[27]   Colombo, G.L., Rossi, E., De Rosa, M., et al. (2012) Antidiabetic Therapy in Real Practice: Indicators for Adherence and Treatment Cost. Patient Preference and Adherence, 6, 653-661.

[28]   Dupclay, L., Eaddy, M., Jackson, J., et al. (2012) Real-World Impact of Reminder Packaging on Antihypertensive Treatment Adherence and Persistence. Patient Preference and Adherence, 6, 499-507.

[29]   Egede, L.E., Gebregziabher, M., Dismuke, C.E., et al. (2012) Medication Nonadherence in Diabetes: Longitudinal Effects on Costs and Potential Cost Savings from Improvement. Diabetes Care, 35, 2533-2539.

[30]   Vollmer, W.M., Feldstein, A., Smith, D.H., et al. (2011) Use of Health Information Technology to Improve Medication Adherence. American Journal of Managed Care, 17, SP79-S87.

[31]   Ratanawongsa, N., Karter, A.J., Parker, M.M., et al. (2013) Communication and Medication Refill Adherence: The Diabetes Study of Northern California. JAMA Internal Medicine, 173, 210-218.

[32]   Kocarnik, B.M., Liu, C.F., Wong, E.S., et al. (2012) Does the Presence of a Pharmacist in Primary Care Clinics Improve Diabetes Medication Adherence? BMC Health Services Research, 12, 391.

[33]   Cocohoba, J.M., Murphy, P., Pietrandoni, G., et al. (2003) Improved Antiretroviral Refill Adherence in HIV-Focused Community Pharmacies. Journal of American Pharmacists Association, 52, e67-e73.

[34]   Sharma, K.P. and Taylor, T.N. (2012) Pharmacy Effect on Adherence to Antidiabetic Medications. Medical Care, 50, 685-691.

[35]   Yeaw, J., Benner, J.S., Walt, J.G., et al. (2009) Comparing Adherence and Persistence across 6 Chronic Medication Classes. Journal of Managed Care Pharmacy, 15, 728-740.

[36]   van den Boogaard, J., Lyimo, R.A., Boeree, M.J., et al. (2011) Electronic Monitoring of Treatment Adherence and Validation of Alternative Adherence Measures in Tuberculosis Patients: A Pilot Study. Bulletin of the World Health Organization, 89, 632-639.

[37]   Gu, Q., Zeng, F., Patel, B.V., et al. (2010) Part D Coverage Gap and Adherence to Diabetes Medications. American Journal of Managed Care, 16, 911-918.

[38]   Egede, L.E., Gebregziabher, M., Hunt, K.J., et al. (2011) Regional, Geographic, and Ethnic Differences in Medication Adherence among Adults with Type 2 Diabetes. The Annals of Pharmacotherapy, 45, 169-178.

[39]   Friedman, D.S., Quigley, H.A., Gelb, L., et al. (2007) Using Pharmacy Claims Data to Study Adherence to Glaucoma Medications: Methodology and Findings of the Glaucoma Adherence and Persistency Study (GAPS). Investigative Ophthalmology & Visual Science, 48, 5052-5057.

[40]   Hess, L.M., Raebel, M.A., Conner, D.A., et al. (2006) Measurement of Adherence in Pharmacy Administrative Databases: A Proposal for Standard Definitions and Preferred Measures. Annals of Pharmacotherapy, 40, 1280-1288.

[41]   Santoleri, F., Sorice, P., Lasala, R., et al. (2013) Patient Adherence and Persistence with Imatinib, Nilotinib, Dasatinib in Clinical Practice. PLoS One, 8, e56813.

[42]   Sattler, E.L., Lee, J.S. and Perri 3rd, M. (2013) Medication (Re)fill Adherence Measures Derived from Pharmacy Claims Data in Older Americans: A Review of the Literature. Drugs & Aging, 30, 383-399.

[43]   Peterson, A.M., Nau, D.P., Cramer, J.A., et al. (2007) A Checklist for Medication Compliance and Persistence Studies Using Retrospective Database. Value in Health, 10, 3-12.

[44]   WHO (2013) Guidelines for ATC Classification and DDD Assignment 2012. Collaborating Centre for Drug Statistics Methodology, Oslo.