Post-initiation predictors of discontinuation of the sodium-glucose cotransporter-2 inhibitors: A comparative cohort study from the United Kingdom.
DPP-4 inhibitor
SGLT2 inhibitor
antidiabetic drug
cohort study
observational study
Journal
Diabetes, obesity & metabolism
ISSN: 1463-1326
Titre abrégé: Diabetes Obes Metab
Pays: England
ID NLM: 100883645
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
revised:
22
07
2023
received:
06
02
2023
accepted:
25
07
2023
medline:
13
11
2023
pubmed:
11
8
2023
entrez:
11
8
2023
Statut:
ppublish
Résumé
To assess post-initiation predictors of discontinuation of sodium-glucose cotransporter-2 (SGLT2) inhibitors compared to dipeptidyl-peptidase-4 (DPP-4) inhibitors in the United Kingdom. We conducted a comparative population-based retrospective cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) with linked data to hospital and death records. We included new metformin users who initiated either SGLT2 inhibitors or DPP-4 inhibitors between January 2013 and October 2019. The main outcome was treatment discontinuation, defined as the first 90-day gap after the estimated treatment end date. We used a series of extended Cox models to assess which time-dependent predictors were associated with treatment discontinuation. To test if the hazard ratio of discontinuation for each predictor was statistically different between SGLT2 and DPP-4 inhibitors, an exposure-predictor interaction term was added to each model. There were 2550 new users of SGLT2 inhibitors and 8195 new users of DPP-4 inhibitors. Approximately 69% of SGLT2 inhibitor and 74% of DPP-4 inhibitor users had discontinued treatment by the end of follow-up. Occurrence of fractures after treatment initiation was a significant predictor of discontinuation of SGLT2 inhibitors (hazard ratio [HR] 4.13, 95% confidence interval [CI] 2.12-8.06) but not DPP-4 inhibitors (HR 0.93, 95% CI 0.79-1.11). The rate of treatment discontinuation was significantly higher for those with low estimated glomerular filtration rate and minimal contact with the healthcare system. Efficacy endpoints, such as heart failure and glycated haemoglobin level, were not associated with treatment discontinuation. Our findings reflect some discrepancy between the available evidence and prescribing behaviour for SGLT2 inhibitors.
Substances chimiques
Dipeptidyl-Peptidase IV Inhibitors
0
Glucose
IY9XDZ35W2
Hypoglycemic Agents
0
Sodium
9NEZ333N27
Sodium-Glucose Transporter 2
0
Sodium-Glucose Transporter 2 Inhibitors
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3490-3500Subventions
Organisme : CIHR
ID : FRN 156064
Pays : Canada
Informations de copyright
© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
Références
EMC. SmPC. Invokana 100 mg and 300 mg film-coated tablets. Accessed on August 2022. https://www.medicines.org.uk/emc/product/8855/smpc.%20Accessed%20on%20Aug%202022
Joint Formulary Committee. British National Formulary 83. BMJ Publishing and the Royal Pharmaceutical Society; 2022.
Bailey CJ. Uric acid and the cardio-renal effects of SGLT2 inhibitors. Diabetes Obes Metab. 2019;21(6):1291-1298.
Majewski C, Bakris GL. Blood pressure reduction: an added benefit of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes. Diabetes Care. 2015;38(3):429-430.
Thomas MC, Cherney DZI. The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure. Diabetologia. 2018 Oct;61(10):2098-2107.
Bonora BM, Avogaro A, Fadini GP. Extraglycemic effects of SGLT2 inhibitors: a review of the evidence. Diabetes Metab Syndr Obes. 2020;21(13):161-174.
Ni L, Yuan C, Chen G, Zhang C, Wu X. SGLT2i: beyond the glucose-lowering effect. Cardiovasc Diabetol. 2020;19(1):98.
National Institute for Health and Care Excellence. Type 2 diabetes in adults: management [NG28]. 2015 Accessed August 2022. https://www.nice.org.uk/guidance/ng28
Pelletier R, Ng K, Alkabbani W, Labib Y, Mourad N, Gamble JM. Adverse events associated with sodium glucose co-transporter 2 inhibitors: an overview of quantitative systematic reviews. Ther Adv Drug Saf. 2021;12:2042098621989134.
Nadkarni GN, Ferrandino R, Chang A, et al. Acute kidney injury in patients on SGLT2 inhibitors: a propensity-matched analysis. Diabetes Care. 2017;40(11):1479-1485.
Alkabbani W, Zongo A, Minhas-Sandhu JK, et al. Renal effectiveness and safety of the sodium-glucose cotransporter-2 inhibitors: a population-based cohort study. BMJ Open Diabetes Res Care. 2021 Dec;9(2):e002496.
Fralick M, Kim SC, Schneeweiss S, Kim D, Redelmeier DA, Patorno E. Fracture risk after initiation of use of canagliflozin: a cohort study. Ann Intern Med. 2019;170(3):155-163.
Abrahami D, Douros A, Yin H, Yu OHY, Azoulay L. Sodium-glucose cotransporter 2 inhibitors and the risk of fractures among patients with type 2 diabetes. Diabetes Care. 2019;42(9):e150-e152.
Zhuo M, Hawley CE, Paik JM, et al. Association of sodium-glucose cotransporter-2 inhibitors with fracture risk in older adults with type 2 diabetes. JAMA Netw Open. 2021;4(10):e2130762.
Dave CV, Schneeweiss S, Kim D, Fralick M, Tong A, Patorno E. Sodium-glucose cotransporter-2 inhibitors and the risk for severe urinary tract infections: a population-based cohort study. Ann Intern Med. 2019;171(4):248-256.
Alkabbani W, Zongo A, Minhas-Sandhu JK, et al. Sodium-glucose cotransporter-2 inhibitors and urinary tract infections: a propensity score-matched population-based cohort study. Can J Diabetes. 2022;46(4):392-403.e13.
Dave CV, Schneeweiss S, Patorno E. Comparative risk of genital infections associated with sodium-glucose co-transporter-2 inhibitors. Diabetes Obes Metab. 2019;21(2):434-438.
Alkabbani W, Zongo A, Minhas-Sandhu JK, et al. Five comparative cohorts to assess the risk of genital tract infections associated with sodium-glucose cotransporter-2 inhibitors initiation in type 2 diabetes mellitus. Diabet Med. 2022;39(8):e14858.
Douros A, Lix LM, Fralick M, et al. Sodium-glucose cotransporter-2 inhibitors and the risk for diabetic ketoacidosis: a multicenter cohort study. Ann Intern Med. 2020;173(6):417-425.
Dawwas GK, Flory JH, Hennessy S, Leonard CE, Lewis JD. Comparative safety of sodium-glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitors and sulfonylureas on the risk of diabetic ketoacidosis. Diabetes Care. 2022;45(4):919-927.
Alkabbani W, Pelletier R, Gamble JM. Sodium/glucose cotransporter 2 inhibitors and the risk of diabetic ketoacidosis: an example of complementary evidence for rare adverse events. Am J Epidemiol. 2021;190(8):1572-1581.
Chang HY, Singh S, Mansour O, Baksh S, Alexander GC. Association between sodium-glucose cotransporter 2 inhibitors and lower extremity amputation among patients with type 2 diabetes. JAMA Intern Med. 2018;178(9):1190-1198.
Heyward J, Mansour O, Olson L, Singh S, Alexander GC. Association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and lower extremity amputation: a systematic review and meta-analysis. PLoS One. 2020;15(6):e0234065.
Yu OHY, Dell'Aniello S, Shah BR, et al. Sodium-glucose cotransporter 2 inhibitors and the risk of below-knee amputation: a multicenter observational study. Diabetes Care. 2020;43(10):2444-2452.
Ofori-Asenso R, Sahle BW, Chin KL, et al. Poor adherence and persistence to sodium glucose co-transporter 2 inhibitors in real-world settings: evidence from a systematic review and meta-analysis. Diabetes Metab Res Rev. 2021 Jan;37(1):e3350.
Ogundipe O, Mazidi M, Chin KL, et al. Real-world adherence, persistence, and in-class switching during use of dipeptidyl peptidase-4 inhibitors: a systematic review and meta-analysis involving 594,138 patients with type 2 diabetes. Acta Diabetol. 2021 Jan;58(1):39-46.
Lee DSU, Lee H. Adherence and persistence rates of major antidiabetic medications: a review. Diabetol Metab Syndr. 2022;14:12.
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):1175-1186.
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):1317-1328.
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 Jun;10(4):165-174.
Coleman CI, Pandya S, Wang L, et al. Treatment patterns, glycemic control and bodyweight with canagliflozin 300 mg versus GLP1RAs in type II diabetes patients. J Comp Eff Res. 2019;8(11):889-905.
Diels J, Neslusan C. Comparative persistency with newer agents used to treat type 2 diabetes (T2DM) in the United States: canagliflozin versus dipeptidyl peptidase-4 (Dpp-4) inhibitors and glucagon-like peptide-1 (Glp-1) agonists. Value Health. 2015;18(3):A68-A69.
Jermendy G, Kiss Z, 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 Oct;9(5):2133-2141.
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):229-242.
Htike ZZ, Lin MZ, Davies MJ, Lawrence IG. Real-life initial experience of using dapagliflozin in a university teaching hospital. Diabet Med. 2015;32(Suppl. 1):173.
Herrett E, Gallagher AM, Bhaskaran K, et al. Data resource profile: clinical practice research datalink (CPRD). Int J Epidemiol. 2015;44(3):827-836.
Herrett E, Thomas SL, Schoonen WM, Smeeth L, Hall AJ. Validation and validity of diagnoses in the general practice research database: a systematic review. Br J Clin Pharmacol. 2010;69:4-14.
Jick SS, Kaye JA, Vasilakis-Scaramozza C, et al. Validity of the general practice research database. Pharmacotherapy. 2003;23:686-689.
Khan NF, Harrison SE, Rose PW. Validity of diagnostic coding within the general practice research database: a systematic review. Br J Gen Pract. 2010;60:e128-e136.
Mathur R, Bhaskaran K, Chaturvedi N, et al. Completeness and usability of ethnicity data in UK-based primary care and hospital databases. J Public Health (Oxf). 2014;36(4):684-692.
Andrade SE, Kahler KH, Frech F, Chan KA. Methods for evaluation of medication adherence and persistence using automated databases. Pharmacoepidemiol Drug Saf. 2006;15(8):565-574. discussion 575-567.
Head A, Fleming K, Kypridemos C, Schofield P, Pearson-Stuttard J, O'Flaherty M. Inequalities in incident and prevalent multimorbidity in England, 2004-19: a population-based, descriptive study. Lancet Healthy Longev. 2021;2(8):e489-e497.
McLennan D, Noble S, Noble M, Plunkett E, Wright G, Gutacker N. The English Indices of Deprivation. Ministry of Housing, Communites & Local Government. Technical report 2019.
Kleinbaum DG, Klein M. Extension of the cox proportional hazards model for time-dependent variables. Survival Analysis. Springer; 2012:241-288.
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644-657.
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295-2306.
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347-357.
Cheng L, Li YY, Hu W, et al. Risk of bone fracture associated with sodium-glucose cotransporter-2 inhibitor treatment: a meta-analysis of randomized controlled trials. Diabetes Metab. 2019;45(5):436-445.
US Food and Drug Administration. FDA Drug Safety Communication: FDA revises label of diabetes drug canagliflozin (Invokana, Invokamet) to include updates on bone fracture risk and new information on decreased bone mineral density. 2016 Accessed January 19, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-revises-label-diabetes-drug-canagliflozin-invokana-invokamet
US Food and Drug Administration. FDA Drug Safety Communication: FDA strengthens kidney warnings for diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR). 2016 Accessed 19 January 19, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-kidney-warnings-diabetes-medicines-canagliflozin
McGovern AP, Hogg M, Shields BM, et al. Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation. BMJ Open Diabetes Res Care. 2020;8(1):e001238.
Morris ZS, Wooding S, Grant J. The answer is 17 years, what is the question: understanding time lags in translational research. J R Soc Med. 2011;104(12):510-520.
Donnan JR, Johnston K, Chibrikov E, et al. Capturing adult patient preferences toward benefits and risks of second-line antihyperglycemic medications used in type 2 diabetes: a discrete choice experiment. Can J Diabetes. 2020;44(1):6-13.
Painter JT, Moore G, Morris B. Addressing Medication Non-Adherence Through Implementation of an Appointment-Based Model Synchronization Network. National Community Pharmacist Assosiation; 2015.
Malik ME, Falkentoft AC, Jensen J, et al. Discontinuation and reinitiation of SGLT-2 inhibitors and GLP-1R agonists in patients with type 2 diabetes: a nationwide study from 2013 to 2021. Lancet Reg Health Eur. 2023;17(29):100617.