Partial non-adherence to antidiabetic therapy undermines diabetes management and correlates with treatment complexity: A cross-sectional study using blood plasma analysis

. 2026 Jan ; 28 (1) : 186-196. [epub] 20251010

Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid41069299

Grantová podpora
IN 00023001 Ministerstvo Zdravotnictví Ceské Republiky : Institute for Clinical and Experimental Medicine-IKEM
IN00023001 Ministerstvo Zdravotnictví Ceské Republiky : Institute for Clinical and Experimental Medicine-IKEM
LX22NPO5104 NextGenerationEU (EXCELES)
SVV 260 785 Univerzita Karlova v Praze
NU20-01-00186 Ministerstvo Zdravotnictví Ceské Republiky
IN 00023001 Institute for Clinical and Experimental Medicine
LX22NPO5104 NextGenerationEU (EXCELES, ID Project No)
NU20-01-00186 Czech Ministry of Health
LX22NPO5104 Programme EXCELES
European Union-Next Generation EU
IN 00023001 Institute for Clinical and Experimental Medicine-IKEM
SVV 260 785 Charles University

AIMS: To evaluate medication adherence in patients with type 2 diabetes (T2D) using plasma drug measurements and assess the clinical impact of partial non-adherence on glycemic control and complications. MATERIALS AND METHODS: This cross-sectional study included 641 T2D outpatients attending routine follow-up visits. After overnight fasting, blood samples were collected and analysed by LC-MS to quantify plasma concentrations of 13 oral antidiabetic drugs. Adherence was defined as the detection of a prescribed drug above the limit of quantification. Self-reported lifestyle factors, dosing regimens, and clinical outcomes were assessed in relation to drug presence. RESULTS: Metformin adherence was very high, with the drug undetected in only 1.9% of patients. In contrast, adherence rates were lower for sulfonylureas (94%), DPP-4 inhibitors (90%), pioglitazone (82%), and SGLT2 inhibitors (73%). Non-adherence was predominantly partial: only one of the analysed antidiabetics taken by patients was not detected in 93% of non-adherent patients. Adherence declined with increasing numbers of prescribed agents and daily doses, suggesting treatment complexity as a key factor. No other tested lifestyle or drug management parameters were significantly associated with adherence. Glycemic control was worse in non-adherent patients: 63% did not reach target glucose and HbA1c levels, compared to 37% of fully adherent patients. Non-adherence was also associated with a higher prevalence of diabetic kidney disease. CONCLUSIONS: Partial non-adherence is common in T2D and strongly associated with treatment complexity and poor glycemic outcomes. These findings emphasize the need for individualized strategies to support adherence and improve long-term diabetes care. Our study further indicates that plasma analysis using LC-MS methods may serve as a robust tool for adherence assessment.

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Dall TM, Yang W, Halder P, et al. The economic burden of elevated blood glucose levels in 2012: diagnosed and undiagnosed diabetes, gestational diabetes mellitus, and prediabetes. Diabetes Care. 2014;37(12):3172‐3179. PubMed

Blonde L, Dipp S, Cadena D. Correction to: combination glucose‐lowering therapy plans in T2DM: case‐based considerations. Adv Ther. 2018;35(7):966. PubMed PMC

Blonde L, Dipp S, Cadena D. Combination glucose‐lowering therapy plans in T2DM: case‐based considerations. Adv Ther. 2018;35(7):939‐965. PubMed PMC

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;10:1299‐1307. PubMed PMC

Vrijens B, de Geest S, Hughes DA, et al. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol. 2012;73(5):691‐705. PubMed PMC

Boonpattharatthiti K, Songkla PN, Chantara J, et al. Prevalence of adherence to oral antidiabetic drugs in patients with type 2 diabetes: a systematic review and meta‐analysis. J Diabetes Investig. 2024;15(11):1614‐1625. PubMed PMC

Shaikh SAA, Kumari J, Bahmanshiri Y. Assessing the adherence to antidiabetic medications among patients diagnosed with type 2 diabetes mellitus in Ajman, UAE. Cureus. 2023;15(11):e49325. PubMed PMC

Hutchins V, Zhang B, Fleurence RL, Krishnarajah G, Graham J. A systematic review of adherence, treatment satisfaction and costs, in fixed‐dose combination regimens in type 2 diabetes. Curr Med Res Opin. 2011;27(6):1157‐1168. PubMed

Hendrychova T, Vytrisalova M, Alwarafi A, et al. Fat‐ and fiber‐related diet behavior among type 2 diabetes patients from distinct regions. Patient Prefer Adherence. 2015;9:319‐325. PubMed PMC

Hendrychova T, Vytrisalova M, Vlcek J, Smahelova A, Kubena AA. An analysis of fat‐related and fiber‐related behavior in men and women with type 2 diabetes mellitus: key findings for clinical practice. Patient Prefer Adherence. 2013;7:877‐884. PubMed PMC

Konstantinou P, Kasinopoulos O, Karashiali C, et al. A scoping review of methods used to assess medication adherence in patients with chronic conditions. Ann Behav Med. 2022;56(12):1201‐1217. PubMed

Nau DP. Recommendations for improving adherence to type 2 diabetes mellitus therapy: focus on optimizing oral and non‐insulin therapies. Am J Manag Care. 2012;18(3 Suppl):S49‐S54. PubMed

el Alili M, Vrijens B, Demonceau J, Evers SM, Hiligsmann M. A scoping review of studies comparing the medication event monitoring system (MEMS) with alternative methods for measuring medication adherence. Br J Clin Pharmacol. 2016;82(1):268‐279. PubMed PMC

Rakusanova S, Cajka T. Current analytical methods to monitor type 2 diabetes medication in biological samples. Trends Anal Chem. 2023;158:116831.

Alquadeib BT, Aloudah NM, Almurshedi AS, et al. Development and validation of a simple and sensitive LC‐MS/MS method for quantification of metformin in dried blood spot its application as an indicator for medication adherence. Int J Gen Med. 2021;14:3225‐3233. PubMed PMC

Groenland EH, van Kleef M, Bots ML, Visseren FLJ, van der Elst KCM, Spiering W. Plasma trough concentrations of antihypertensive drugs for the assessment of treatment adherence: a meta‐analysis. Hypertension. 2021;77(1):85‐93. PubMed PMC

Denicolo S, Reinstadler V, Keller F, et al. Non‐adherence to cardiometabolic medication as assessed by LC‐MS/MS in urine and its association with kidney and cardiovascular outcomes in type 2 diabetes mellitus. Diabetologia. 2024;67(7):1283‐1294. PubMed PMC

Wang Y, Wang JW, Wang Y, et al. Monitoring antihypertensive medication adherence by liquid chromatography‐tandem mass spectrometry: method establishment and clinical application. J Cardiovasc Pharmacol. 2021;78(4):581‐596. PubMed

Mohamed D, Elshahed MS, Nasr T, Aboutaleb N, Zakaria O. Novel LC‐MS/MS method for analysis of metformin and canagliflozin in human plasma: application to a pharmacokinetic study. BMC Chem. 2019;13(1):82. PubMed PMC

Team RC . A Language and Environment for Statistical Computing. R Foundation for Statistical Computing Vienna, Austria. 2023.

Wickham HAM, Bryan J, Chang W, et al. Welcome to the {tidyverse}. J Open Source Softw. 2019;4(43):1686.

Le S, Josse J, Husson F. FactoMineR: an R package for multivariate analysis. J Stat Softw. 2008;25(1):1‐18.

Schulz M, Schmoldt A, Andresen‐Streichert H, Iwersen‐Bergmann S. Revisited: therapeutic and toxic blood concentrations of more than 1100 drugs and other xenobiotics. Crit Care. 2020;24(1):195. PubMed PMC

Thayer S, Arondekar B, Harley C, Darkow TE. Adherence to a fixed‐dose combination of rosiglitazone/glimepiride in subjects switching from monotherapy or dual therapy with a thiazolidinedione and/or a sulfonylurea. Ann Pharmacother. 2010;44(5):791‐799. PubMed

Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of diabetes (EASD). Diabetologia. 2022;65(12):1925‐1966. PubMed PMC

Janez A, Guja C, Mitrakou A, et al. Insulin therapy in adults with type 1 diabetes mellitus: a narrative review. Diabetes Ther. 2020;11(2):387‐409. PubMed PMC

Kim SH. Reframing prediabetes: a call for better risk stratification and intervention. J Intern Med. 2024;295(6):735‐747. PubMed

American Diabetes A . Standards of medical Care in Diabetes‐2022 abridged for primary care providers. Clin Diabetes. 2022;40(1):10‐38. PubMed PMC

Hameed MA, Dasgupta I. Medication adherence and treatment‐resistant hypertension: a review. Drugs Context. 2019;8:212560. PubMed PMC

Lam WY, Fresco P. Medication adherence measures: an overview. Biomed Res Int. 2015;2015:217047. PubMed PMC

Paschal AM, Hawley SR, St Romain T, Ablah E. Measures of adherence to epilepsy treatment: review of present practices and recommendations for future directions. Epilepsia. 2008;49(7):1115‐1122. PubMed

Hartman L, Lems WF, Boers M. Outcome measures for adherence data from a medication event monitoring system: a literature review. J Clin Pharm Ther. 2019;44(1):1‐5. PubMed PMC

Gadkari AS, McHorney CA. Unintentional non‐adherence to chronic prescription medications: how unintentional is it really? BMC Health Serv Res. 2012;12:98. PubMed PMC

Fahrni ML, Saman KM, Alkhoshaiban AS, Naimat F, Ramzan F, Isa KAM. Patient‐reported outcome measures to detect intentional, mixed, or unintentional non‐adherence to medication: a systematic review. BMJ Open. 2022;12(9):e057868. PubMed PMC

Gooptu A, Taitel M, Laiteerapong N, Press VG. Association between medication non‐adherence and increases in hypertension and type 2 diabetes medications. Healthcare (Basel). 2021;9(8):976. PubMed PMC

Farmer KC. Methods for measuring and monitoring medication regimen adherence in clinical trials and clinical practice. Clin Ther. 1999;21(6):1074‐1090. discussion 1073. PubMed

Berra E, Azizi M, Capron A, et al. Evaluation of adherence should become an integral part of assessment of patients with apparently treatment‐resistant hypertension. Hypertension. 2016;68(2):297‐306. PubMed

Vlacho B, Mata‐Cases M, Mundet‐Tuduri X, et al. Analysis of the adherence and safety of second oral glucose‐lowering therapy in routine practice from the Mediterranean area: a retrospective cohort study. Front Endocrinol (Lausanne). 2021;12:708372. PubMed PMC

Rea F, Ciardullo S, Savaré L, Perseghin G, Corrao G. Comparing medication persistence among patients with type 2 diabetes using sodium‐glucose cotransporter 2 inhibitors or glucagon‐like peptide‐1 receptor agonists in real‐world setting. Diabetes Res Clin Pract. 2021;180:109035. PubMed

Jermendy G, Kiss Z, Rokszin G, Abonyi‐Toth 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. PubMed PMC

Strain WD, Tsang C, Hurst M, et al. What next after metformin in type 2 diabetes? Selecting the right drug for the right patient. Diabetes Ther. 2020;11(6):1381‐1395. PubMed PMC

Li D, Wang T, Shen S, Fang Z, Dong Y, Tang H. Urinary tract and genital infections in patients with type 2 diabetes treated with sodium‐glucose co‐transporter 2 inhibitors: a meta‐analysis of randomized controlled trials. Diabetes Obes Metab. 2017;19(3):348‐355. PubMed

Buse JB, Wexler DJ, Tsapas A, et al. Correction to: 2019 update to: management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of diabetes (EASD). Diabetologia. 2020;63(8):1667. PubMed

Buse JB, Wexler DJ, Tsapas A, et al. 2019 update to: management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of diabetes (EASD). Diabetologia. 2020;63(2):221‐228. PubMed

Paes AH, Bakker A, Soe‐Agnie CJ. Impact of dosage frequency on patient compliance. Diabetes Care. 1997;20(10):1512‐1517. PubMed

Leong AY, Sanghera R, Jhajj J, Desai N, Jammu BS, Makowsky MJ. Is YouTube useful as a source of health information for adults with type 2 diabetes? A south Asian perspective. Can J Diabetes. 2018;42(4): 395–403. PubMed

Ali MK, McKeever Bullard K, Imperatore G, et al. Characteristics associated with poor glycemic control among adults with self‐reported diagnosed diabetes: National Health and nutrition examination survey, United States, 2007–2010. MMWR. 2012;61(2):32‐37. PubMed

Wong ND, Patao C, Wong K, Malik S, Franklin SS, Iloeje U. Trends in control of cardiovascular risk factors among US adults with type 2 diabetes from 1999 to 2010: comparison by prevalent cardiovascular disease status. Diab Vasc Dis Res. 2013;10(6):505‐513. PubMed PMC

Yorek M. Combination therapy is it in the future for successfully treating peripheral diabetic neuropathy? Front Endocrinol (Lausanne). 2024;15:1357859. PubMed PMC

Diaz E, Levine HB, Sullivan MC, et al. Use of the Medication Event Monitoring System to estimate medication compliance in patients with schizophrenia. J Psychiatry Neurosci. 2001;26(4):325‐329. PubMed PMC

Modi AC, Ingerski LM, Rausch JR, Glauser TA, Drotar D. White coat adherence over the first year of therapy in pediatric epilepsy. J Pediatr. 2012;161(4): 695–699. PubMed PMC

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