Non-adherence and non-persistence to diabetes medications are associated with worse clinical outcomes. In this study, we aimed to characterise the 1-year switching, adherence, and persistence patterns among people with diabetes aged 18 years and older prescribed sodium-glucose co-transporter 2 inhibitors (SGLT2is) in Australia.
Using data from Australia’s national Pharmaceutical Benefits Scheme (PBS), we identified 11,981 adults (mean age 60.9 years; 40.5% female) newly initiated on SGLT2is (5993 dapagliflozin; 5988 empagliflozin) from September 2015 to August 2017. Adherence was assessed via the proportion of days covered (PDC), persistence was defined as the continuous use of SGLT2i without a gap of ≥ 90 days, and switching was defined as the first change from dapagliflozin to empagliflozin or vice versa. Generalised linear models (GLMs) were used to compare the adherence (PDC = continuous), logistic regression models were used to compare the likelihoods of being adherent (PDC ≥ 0.80), and Cox proportional hazard models were used to compare the likelihoods of persistence and switching between people prescribed empagliflozin and dapagliflozin.
Overall, 65.8% (7879/11,981) of people dispensed SGLT2is were adherent (PDC ≥ 0.80) and 72.1% (8644/11,981) were persistent at 12 months. The mean PDC was 0.79 ± 0.27. The use of empagliflozin was associated with higher adherence (PDC = continuous) [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.03–1.05], being adherent (OR 1.39, 95% CI 1.29–1.51), and persisting for 12 months [hazard ratio (HR) 1.14, 95% CI 1.06–1.22] compared with dapagliflozin. Only 4.3% (509/11,981) of people switched between the SGLT2i. Compared with dapagliflozin, people initiated on empagliflozin were less likely to switch [HR 0.46, 95% CI 0.38–0.55].
A considerable proportion of Australians prescribed SGLT2is were non-adherent or non-persistent. However, empagliflozin was associated with better adherence and persistence rates and a lower likelihood of switching compared with dapagliflozin.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Zimmet PZ. Diabetes and its drivers: the largest epidemic in human history? Clin Diabetes Endocrinol. 2017;3:1.
Diabetes facts & figures. https://www.idf.org/aboutdiabetes/what-is-diabetes/facts-figures.html. Accessed 5 May 2019
Burden of diabetes in Australia: its time for more action. http://www.novonordisk.com.au/content/dam/australia/affiliate/www-novonordisk-au/Home/Documents/180712_Burden%20of%20Diabetes_Its%20Time%20for%20More%20Action%20Report_Digital_%20FINAL….pdf. Accessed 10 May 2019
Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: distinct or continuum? Indian J Endocrinol Metab. 2016;20(4):546–51.
Fowler M. Microvascular and macrovascular complications of diabetes. Clin Diabetes. 2008;26(2):77–82.
Federal election 2013: a national diabetes strategy and action plan. https://static.diabetesaustralia.com.au/s/fileassets/diabetes-australia/e549bdb8-0f80-46f8-b827-35cb4f1b6cd2.pdf. Accessed 10 May 2019
Lee CM, Colagiuri R, Magliano DJ, Cameron AJ, Shaw J, Zimmet P, Colagiuri S. The cost of diabetes in adults in Australia. Diabetes Res Clin Pract. 2013;99(3):385–90.
Sherwani SI, Khan HA, Ekhzaimy A, Masood A, Sakharkar MK. Significance of HbA1c test in diagnosis and prognosis of diabetic patients. Biomark Insights. 2016;11:95–104.
Lachin JM, Orchard TJ, Nathan DM, Group DER. Update on cardiovascular outcomes at 30 years of the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care. 2014;37(1):39–43.
Whaley-Connell A, Sowers JR. Implications for glucose measures in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes. 2014;63(1):45–7.
Marathe PH, Gao HX, Close KL. American Diabetes Association standards of medical care in diabetes 2017. J Diabetes. 2017;9(4):320–4.
American Diabetes A. Standards of medical care in diabetes—2019 abridged for primary care providers. Clin Diabetes. 2019;37(1):11–34.
Raval AD, Vyas A. National trends in diabetes medication use in the United States: 2008 to 2015. J Pharm Pract. 2018. https://doi.org/10.1177/0897190018815048
Mann DM, Woodward M, Ye F, Krousel-Wood M, Muntner P. Trends in medication use among US adults with diabetes mellitus: glycemic control at the expense of controlling cardiovascular risk factors. Arch Intern Med. 2009;169(18):1718–20.
Sharma M, Nazareth I, Petersen I. Trends in incidence, prevalence and prescribing in type 2 diabetes mellitus between 2000 and 2013 in primary care: a retrospective cohort study. BMJ Open. 2016;6(1):e010210.
Krass I, Schieback P, Dhippayom T. Adherence to diabetes medication: a systematic review. Diabet Med. 2015;32(6):725–37.
McGovern A, Tippu Z, Hinton W, Munro N, Whyte M, de Lusignan S. Comparison of medication adherence and persistence in type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab. 2018;20(4):1040–3.
Cramer JA. A systematic review of adherence with medications for diabetes. Diabetes Care. 2004;27(5):1218–24.
Lee WC, Balu S, Cobden D, Joshi AV, Pashos CL. Prevalence and economic consequences of medication adherence in diabetes: a systematic literature review. Manag Care Interface. 2006;19(7):31–41.
Egede LE, Gebregziabher M, Dismuke CE, Lynch CP, Axon RN, Zhao Y, Mauldin PD. Medication nonadherence in diabetes: longitudinal effects on costs and potential cost savings from improvement. Diabetes Care. 2012;35(12):2533–9.
Cutler RL, Fernandez-Llimos F, Frommer M, Benrimoj C, Garcia-Cardenas V. Economic impact of medication non-adherence by disease groups: a systematic review. BMJ Open. 2018;8(1):e016982.
Chin KL, Ofori-Asenso R, Hopper I, von Lueder TG, Reid CM, Zoungas S, Wang BH, Liew D. Potential mechanisms underlying the cardiovascular benefits of sodium glucose cotransporter 2 inhibitors: a systematic review of data from preclinical studies. Cardiovasc Res. 2019;115(2):266–76.
Peene B, Benhalima K. Sodium glucose transporter protein 2 inhibitors: focusing on the kidney to treat type 2 diabetes. Ther Adv Endocrinol Metab. 2014;5(5):124–36.
Pioli MR, Ritter AMV, Modolo R. Unsweetening the heart: possible pleiotropic effects of SGLT2 inhibitors on cardio and cerebrovascular alterations in resistant hypertensive subjects. Am J Hypertens. 2018;31(3):274–80.
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.
Kosiborod M, Cavender MA, Fu AZ, Wilding JP, Khunti K, Holl RW, Norhammar A, Birkeland KI, Jorgensen ME, Thuresson M, et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors). Circulation. 2017;136(3):249–59.
Kosiborod M, Lam CSP, Kohsaka S, Kim DJ, Karasik A, Shaw J, Tangri N, Goh SY, Thuresson M, Chen H, et al. Cardiovascular events associated with SGLT-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL 2 study. J Am Coll Cardiol. 2018;71(23):2628–39.
Invoka (Canagliflozin) removal from the pharmaceutical benefits scheme on 1 August 2015. https://www.endocrinesociety.org.au/documents/INVOKANADHCPLFeb16removalPBS.pdf. Accessed 12 May 2019
A new blood glucose management algorithm for type 2 diabetes A position statement of the Australian Diabetes Society. https://diabetessociety.com.au/documents/ADSPOSITIONSTATEMENTv2.12016Uploadedtowebsite.pdf. Accessed 15 May 2019
Medicines for the treatment of diabetes. http://www.pbs.gov.au/industry/listing/participants/public-release-docs/2017-02/diabetes-dusc-prd-2017-02.pdf. Accessed 5 May 2019
Mellish L, Karanges EA, Litchfield MJ, Schaffer AL, Blanch B, Daniels BJ, Segrave A, Pearson SA. The Australian pharmaceutical benefits scheme data collection: a practical guide for researchers. BMC Res Notes. 2015;8:634.
Ofori-Asenso R, Ilomaki J, Tacey M, Zomer E, Curtis AJ, Bell JS, Zoungas S, Liew D. Patterns of statin use and long-term adherence and persistence among older adults with diabetes. J Diabetes. 2018;10(9):699–707.
Ofori-Asenso R, Ilomaki J, Tacey M, Si S, Curtis AJ, Zomer E, Bell JS, Zoungas S, Liew D. Predictors of first-year nonadherence and discontinuation of statins among older adults: a retrospective cohort study. Br J Clin Pharmacol. 2019;85(1):227–35.
Ofori-Asenso R, Ilomaki J, Zomer E, Curtis AJ, Zoungas S, Liew D. A 10-year trend in statin use among older adults in Australia: an analysis using national pharmacy claims data. Cardiovasc Drugs Ther. 2018;32(3):265–72.
Ofori-Asenso R, Ilomaki J, Tacey M, Zomer E, Curtis AJ, Si S, Zullo AR, Korhonen MJ, Bell JS, Zoungas S, et al. Switching, discontinuation, and reinitiation of statins among older adults. J Am Coll Cardiol. 2018;72(21):2675–7.
McGovern A, Hinton W, Calderara S, Munro N, Whyte M, de Lusignan S. A class comparison of medication persistence in people with type 2 diabetes: a retrospective observational study. Diabetes Ther. 2018;9(1):229–42.
Rascati KL, Worley K, Meah Y, Everhart D. Adherence, persistence, and health care costs for patients receiving dipeptidyl peptidase-4 inhibitors. J Manag Care Spec Pharm. 2017;23(3):299–306.
Karve S, Cleves MA, Helm M, Hudson TJ, West DS, Martin BC. Prospective validation of eight different adherence measures for use with administrative claims data among patients with schizophrenia. Value Health. 2009;12(6):989–95.
Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA, Wong PK. Medication compliance and persistence: terminology and definitions. Value Health. 2008;11(1):44–7.
Karve S, Cleves MA, Helm M, Hudson TJ, West DS, Martin BC. Good and poor adherence: optimal cut-point for adherence measures using administrative claims data. Curr Med Res Opin. 2009;25(9):2303–10.
Lam WY, Fresco P. Medication adherence measures: an overview. Biomed Res Int. 2015;2015:217047.
Farr AM, Sheehan JJ, Curkendall SM, Smith DM, Johnston SS, Kalsekar I. Retrospective analysis of long-term adherence to and persistence with DPP-4 inhibitors in US adults with type 2 diabetes mellitus. Adv Ther. 2014;31(12):1287–305.
Ofori-Asenso R, Ilomaki J, Tacey M, Zomer E, Curtis AJ, Bell JS, Zoungas S, Liew D. Predictors of statin use among older adults: a nationwide cross-sectional study. J Clin Lipidol. 2019;13(1):156–62 (e151).
Vaduganathan M, Sathiyakumar V, Singh A, McCarthy CP, Qamar A, Januzzi JL Jr, Scirica BM, Butler J, Cannon CP, Bhatt DL. Prescriber patterns of SGLT2i after expansions of U S Food and Drug Administration labeling. J Am Coll Cardiol. 2018;72(25):3370–2.
Shyangdan DS, Uthman OA, Waugh N. SGLT-2 receptor inhibitors for treating patients with type 2 diabetes mellitus: a systematic review and network meta-analysis. BMJ Open. 2016;6(2):e009417.
Tahara A, Takasu T, Yokono M, Imamura M, Kurosaki E. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors in pharmacokinetics, pharmacodynamics, and pharmacologic effects. J Pharmacol Sci. 2016;130(3):159–69.
Garcia-Perez LE, Alvarez M, Dilla T, Gil-Guillen V, Orozco-Beltran D. Adherence to therapies in patients with type 2 diabetes. Diabetes Ther. 2013;4(2):175–94.
Polonsky WH, Henry RR. Poor medication adherence in type 2 diabetes: recognizing the scope of the problem and its key contributors. Patient Prefer Adherence. 2016;10:1299–307.
Ho PM, Rumsfeld JS, Masoudi FA, McClure DL, Plomondon ME, Steiner JF, Magid DJ. Effect of medication nonadherence on hospitalization and mortality among patients with diabetes mellitus. Arch Intern Med. 2006;166(17):1836–41.
Currie CJ, Peyrot M, Morgan CL, Poole CD, Jenkins-Jones S, Rubin RR, Burton CM, Evans M. The impact of treatment noncompliance on mortality in people with type 2 diabetes. Diabetes Care. 2012;35(6):1279–84.
Cai J, Divino V, Burudpakdee C. Adherence and persistence in patients with type 2 diabetes mellitus newly initiating canagliflozin, dapagliflozin, dpp-4s, or glp-1s in the United States. Curr Med Res Opin. 2017;33(7):1317–28.
Cai J, Wang Y, Baser O, Xie L, Chow W. Comparative persistence and adherence with newer anti-hyperglycemic agents to treat patients with type 2 diabetes in the United States. J Med Econ. 2016;19(12):1175–86.
Bell KF, Cappell K, Liang M, Kong AM. Comparing medication adherence and persistence among patients with type 2 diabetes using sodium-glucose cotransporter 2 inhibitors or sulfonylureas. Am Health Drug Benefits. 2017;10(4):165–74.
Nishimura R, Kato H, Kisanuki K, Oh A, Hiroi S, Onishi Y, Guelfucci F, Shimasaki Y. Treatment patterns, persistence and adherence rates in patients with type 2 diabetes mellitus in Japan: a claims-based cohort study. BMJ Open. 2019;9(3):e025806.
Jermendy G, Rokszin G, Abonyi-Tóth Z, Wittmann I, Kempler P. Persistence to treatment with novel antidiabetic drugs (Dipeptidyl Peptidase-4 Inhibitors, Sodium-Glucose Co-Transporter-2 Inhibitors, and Glucagon-Like Peptide-1 Receptor Agonists) in people with type 2 diabetes: a nationwide cohort study. Diabetes Ther. 2018;9(5):2133–2141.
Sharkey N, Maxwell P. Will Sglt2 inhibitors prove to be a ‘multiple’ gamechanger? Ulster Med J. 2019;88(1):8–9.
Kumana CR, Tan KCB, Cheung BMY. Absolute benefits of empagliflozin in type 2 diabetes: a game changer? Postgrad Med J. 2017;93(1101):373–5.
Vervloet M, van Dijk L, de Bakker DH, Souverein PC, Santen-Reestman J, van Vlijmen B, van Aarle MC, van der Hoek LS, Bouvy ML. Short- and long-term effects of real-time medication monitoring with short message service (SMS) reminders for missed doses on the refill adherence of people with Type 2 diabetes: evidence from a randomized controlled trial. Diabet Med. 2014;31(7):821–8.
Choudhry NK, Fischer MA, Avorn J, Liberman JN, Schneeweiss S, Pakes J, Brennan TA, Shrank WH. The implications of therapeutic complexity on adherence to cardiovascular medications. Arch Intern Med. 2011;171(9):814–22.
Lindenmeyer A, Hearnshaw H, Vermeire E, Van Royen P, Wens J, Biot Y. Interventions to improve adherence to medication in people with type 2 diabetes mellitus: a review of the literature on the role of pharmacists. J Clin Pharm Ther. 2006;31(5):409–19.
Schoenthaler A, Cuffee Y. A systematic review of interventions to improve adherence to diabetes medications within the patient-practitioner interaction. J Clin Outcomes Manag. 2013;20(11):494–506.
Sapkota S, Brien JA, Greenfield J, Aslani P. A systematic review of interventions addressing adherence to anti-diabetic medications in patients with type 2 diabetes—impact on adherence. PLoS One. 2015;10(2):e0118296.
Williams JL, Walker RJ, Smalls BL, Campbell JA, Egede LE. Effective interventions to improve medication adherence in type 2 diabetes: a systematic review. Diabetes Manag. 2014;4(1):29–48.
Si S, Ofori-Asenso R, Briffa T, Sanfilippo FM, Ilomaki J, Qin X, Tacey M, Reid CM, Liew D. Long-term persistence and adherence to blood pressure lowering agents among older Australians. Pharmacoepidemiol Drug Saf. 2019;28(6):788–95.
Si S, Ofori-Asenso R, Briffa T, Ilomaki J, Sanfilippo F, Reid CM, Liew D. Dispensing patterns of blood pressure lowering agents in older Australians from 2006 to 2016. J Cardiovasc Pharmacol Ther. 2019;24(3):242–50.
Li X, Cole SR, Westreich D, Brookhart MA. Primary non-adherence and the new-user design. Pharmacoepidemiol Drug Saf. 2018;27(4):361–4.
Ray WA. Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol. 2003;158(9):915–20.
Scheen AJ. An update on the safety of SGLT2 inhibitors. Expert Opin Drug Saf. 2019;18(4):295–311.
The authors are grateful to the Australian Government Department of Human Services for providing the Pharmaceutical Benefits Scheme (PBS) data set that was used in this study.
No funding or sponsorship was received for this study or publication of this article.
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Danny Liew reports past participation in advisory boards and/or receiving honoraria from Abbvie, Astellas, AstraZeneca, Bristol-Myers Squibb, Novartis, Pfizer, Sanofi, and Shire for work unrelated to this study. Dianna J. Magliano reports past participation in advisory boards and/or receiving honoraria from AstraZeneca and Bayer for work unrelated to this study. Richard Ofori-Asenso is now also affilitated with Copenhagen Centre for Regulatory Science (CORS), Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Samanta Lalic, Mohsen Mazidi, Zanfina Ademi, J. Simon Bell and Jenni Ilomaki have nothing to disclose.
Compliance with Ethics Guidelines
This article does not contain any new studies with human or animal subjects performed by any of the authors; as such, informed consent of individuals was not required. The study was approved by the Monash University Human research Ethics Committee and the analysis plan was noted by the Australian Government Department of Human Services.
The data used for the analysis can be obtained by direct application to the Australian Government department of Health.
Enhanced Digital Features
To view enhanced digital features for this article go to https://doi.org/10.6084/m9.figshare.9712703.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Ofori-Asenso, R., Liew, D., Lalic, S. et al. Adherence, Persistence, and Switching Among People Prescribed Sodium Glucose Co-transporter 2 Inhibitors: A Nationwide Retrospective Cohort Study. Adv Ther 36, 3265–3278 (2019). https://doi.org/10.1007/s12325-019-01077-3
- SGLT2 inhibitors