Adherence to Antidiabetic Medication and Cardiovascular Outcomes in Cancer Patients: A Nationwide Population-Based Cohort Study
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Ethical Statement
2.2. Study Design and Study Participants
2.3. Assessing Adherence to Antidiabetic Medication
2.4. Determining Study Outcome
2.5. Statistical Analyses
3. Results
3.1. Baseline Characteristics
3.2. Primary Outcomes: Association of Antidiabetic Medication Adherence and All-Cause and CV Mortality
3.3. Secondary Outcomes: Association of Antidiabetic Drug Adherence with a CVD Occurrence
3.4. Ancillary Analysis: Healthcare Expenditure Based on Antidiabetic Medication Adherence
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [PubMed]
- Miller, K.D.; Nogueira, L.; Devasia, T.; Mariotto, A.B.; Yabroff, K.R.; Jemal, A.; Kramer, J.; Siegel, R.L. Cancer treatment and survivorship statistics, 2022. CA Cancer J. Clin. 2022, 72, 409–436. [Google Scholar] [CrossRef]
- Raisi-Estabragh, Z.; Manisty, C.H.; Cheng, R.K.; Lopez Fernandez, T.; Mamas, M.A. Burden and prognostic impact of cardiovascular disease in patients with cancer. Heart 2023, 109, 1819–1826. [Google Scholar] [CrossRef] [PubMed]
- Ahn, Y.; Jung, M.H. Cardiovascular health is the essential but overlooked aspect in the management of cancer survivors. Eur. J. Prev. Cardiol. 2022, 29, 2322–2323. [Google Scholar] [PubMed]
- Strongman, H.; Gadd, S.; Matthews, A.; Mansfield, K.E.; Stanway, S.; Lyon, A.R.; Dos-Santos-Silva, I.; Smeeth, L.; Bhaskaran, K. Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: A population-based cohort study using multiple linked UK electronic health records databases. Lancet 2019, 394, 1041–1054. [Google Scholar]
- Youn, J.C.; Chung, W.B.; Ezekowitz, J.A.; Hong, J.H.; Nam, H.; Kyoung, D.S.; Kim, I.C.; Lyon, A.R.; Kang, S.M.; Jung, H.O.; et al. Cardiovascular disease burden in adult patients with cancer: An 11-year nationwide population-based cohort study. Int. J. Cardiol. 2020, 317, 167–173. [Google Scholar] [CrossRef]
- Johnson, C.B.; Davis, M.K.; Law, A.; Sulpher, J. Shared Risk Factors for Cardiovascular Disease and Cancer: Implications for Preventive Health and Clinical Care in Oncology Patients. Can. J. Cardiol. 2016, 32, 900–907. [Google Scholar]
- Chung, W.B.; Youn, J.C.; Youn, H.J. Cardiovascular Complications of Novel Anti-Cancer Immunotherapy: Old Problems from New Agents? Korean Circ. J. 2020, 50, 743–753. [Google Scholar]
- Kim, D.Y.; Park, M.S.; Youn, J.C.; Lee, S.; Choi, J.H.; Jung, M.H.; Kim, L.S.; Kim, S.H.; Han, S.; Ryu, K.H. Development and Validation of a Risk Score Model for Predicting the Cardiovascular Outcomes After Breast Cancer Therapy: The CHEMO-RADIAT Score. J. Am. Heart Assoc. 2021, 10, e021931. [Google Scholar]
- Jung, M.H.; Yi, S.W.; An, S.J.; Yi, J.J.; Ihm, S.H.; Han, S.; Ryu, K.H.; Jung, H.O.; Youn, H.J. Associations between the triglyceride-glucose index and cardiovascular disease in over 150,000 cancer survivors: A population-based cohort study. Cardiovasc. Diabetol. 2022, 21, 52. [Google Scholar]
- Weaver, K.E.; Foraker, R.E.; Alfano, C.M.; Rowland, J.H.; Arora, N.K.; Bellizzi, K.M.; Hamilton, A.S.; Oakley-Girvan, I.; Keel, G.; Aziz, N.M. Cardiovascular risk factors among long-term survivors of breast, prostate, colorectal, and gynecologic cancers: A gap in survivorship care? J. Cancer Surviv. 2013, 7, 253–261. [Google Scholar] [PubMed]
- Davis, M.K.; Rajala, J.L.; Tyldesley, S.; Pickles, T.; Virani, S.A. The Prevalence of Cardiac Risk Factors in Men with Localized Prostate Cancer Undergoing Androgen Deprivation Therapy in British Columbia, Canada. J. Oncol. 2015, 2015, 820403. [Google Scholar] [PubMed]
- Shahid, R.K.; Ahmed, S.; Le, D.; Yadav, S. Diabetes and Cancer: Risk, Challenges, Management and Outcomes. Cancers 2021, 13, 5375. [Google Scholar] [CrossRef]
- van de Poll-Franse, L.V.; Houterman, S.; Janssen-Heijnen, M.L.; Dercksen, M.W.; Coebergh, J.W.; Haak, H.R. Less aggressive treatment and worse overall survival in cancer patients with diabetes: A large population based analysis. Int. J. Cancer 2007, 120, 1986–1992. [Google Scholar]
- Zanders, M.M.; Haak, H.R.; van Herk-Sukel, M.P.; van de Poll-Franse, L.V.; Johnson, J.A. Impact of cancer on adherence to glucose-lowering drug treatment in individuals with diabetes. Diabetologia 2015, 58, 951–960. [Google Scholar] [PubMed]
- Tan, X.; Feng, X.; Chang, J.; Higa, G.; Wang, L.; Leslie, D. Oral antidiabetic drug use and associated health outcomes in cancer patients. J. Clin. Pharm. Ther. 2016, 41, 524–531. [Google Scholar]
- Choe, S.; Lee, J.; Park, J.W.; Jeong, S.Y.; Cho, Y.M.; Park, B.J.; Shin, A. Prognosis of Patients with Colorectal Cancer with Diabetes According to Medication Adherence: A Population-Based Cohort Study. Cancer Epidemiol. Biomark. Prev. 2020, 29, 1120–1127. [Google Scholar]
- Lee, J.; Lee, J.S.; Park, S.H.; Shin, S.A.; Kim, K. Cohort Profile: The National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. Int. J. Epidemiol. 2017, 46, e15. [Google Scholar]
- Jung, M.H.; Lee, S.Y.; Youn, J.C.; Chung, W.B.; Ihm, S.H.; Kang, D.; Kyoung, D.S.; Jung, H.O.; Chang, K.; Youn, H.J.; et al. Antihypertensive Medication Adherence and Cardiovascular Outcomes in Patients with Cancer: A Nationwide Population-Based Cohort Study. J. Am. Heart Assoc. 2023, 12, e029362. [Google Scholar]
- Hess, L.M.; Raebel, M.A.; Conner, D.A.; Malone, D.C. Measurement of adherence in pharmacy administrative databases: A proposal for standard definitions and preferred measures. Ann. Pharmacother. 2006, 40, 1280–1288. [Google Scholar]
- Yang, Y.S.; Kim, H.L.; Kim, S.H.; Moon, M.K. Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement. J. Lipid Atheroscler. 2023, 12, 12–22. [Google Scholar] [PubMed]
- Jin, E.S.; Shim, J.S.; Kim, S.E.; Bae, J.H.; Kang, S.; Won, J.C.; Shin, M.J.; Jin, H.Y.; Moon, J.; Lee, H.; et al. Dyslipidemia Fact Sheet in South Korea, 2022. J. Lipid Atheroscler. 2023, 12, 237–251. [Google Scholar]
- Lee, H.Y. Heart Failure and Diabetes Mellitus: Dangerous Liaisons. Int. J. Heart Fail. 2022, 4, 163–174. [Google Scholar] [PubMed]
- Lee, K.S.; Noh, J.; Park, S.M.; Choi, K.M.; Kang, S.M.; Won, K.C.; Cho, H.J.; Moon, M.K. Evaluation and Management of Patients with Diabetes and Heart Failure: A Korean Diabetes Association and Korean Society of Heart Failure Consensus Statement. Int. J. Heart Fail. 2023, 47, 10–26. [Google Scholar]
- Youn, J.C.; Kim, D.; Cho, J.Y.; Cho, D.H.; Park, S.M.; Jung, M.H.; Hyun, J.; Cho, H.J.; Park, S.M.; Choi, J.O.; et al. Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Treatment. Int. J. Heart Fail. 2023, 5, 66–81. [Google Scholar] [PubMed]
- Park, S.M.; Lee, S.Y.; Jung, M.H.; Youn, J.C.; Kim, D.; Cho, J.Y.; Cho, D.H.; Hyun, J.; Cho, H.J.; Park, S.M.; et al. Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Management of the Underlying Etiologies and Comorbidities of Heart Failure. Int. J. Heart Fail. 2023, 5, 127–145. [Google Scholar]
- Khunti, K.; Seidu, S.; Kunutsor, S.; Davies, M. Association Between Adherence to Pharmacotherapy and Outcomes in Type 2 Diabetes: A Meta-analysis. Diabetes Care 2017, 40, 1588–1596. [Google Scholar]
- Kim, Y.Y.; Lee, J.S.; Kang, H.J.; Park, S.M. Effect of medication adherence on long-term all-cause-mortality and hospitalization for cardiovascular disease in 65,067 newly diagnosed type 2 diabetes patients. Sci. Rep. 2018, 8, 12190. [Google Scholar]
- Hong, J.S.; Kang, H.C. Relationship between oral antihyperglycemic medication adherence and hospitalization, mortality, and healthcare costs in adult ambulatory care patients with type 2 diabetes in South Korea. Med. Care 2011, 49, 378–384. [Google Scholar]
- Calip, G.S.; Hubbard, R.A.; Stergachis, A.; Malone, K.E.; Gralow, J.R.; Boudreau, D.M. Adherence to oral diabetes medications and glycemic control during and following breast cancer treatment. Pharmacoepidemiol. Drug Saf. 2015, 24, 75–85. [Google Scholar]
- Calip, G.S.; Elmore, J.G.; Boudreau, D.M. Characteristics associated with nonadherence to medications for hypertension, diabetes, and dyslipidemia among breast cancer survivors. Breast Cancer Res. Treat. 2017, 161, 161–172. [Google Scholar] [PubMed]
- Shin, J.Y.; Shim, H.Y.; Jun, J.K. Comparison of diabetes management status between cancer survivors and the general population: Results from a Korean population-based survey. PLoS ONE 2014, 9, e110412. [Google Scholar]
- Jung, M.H.; Yi, S.W.; An, S.J.; Yi, J.J.; Ihm, S.H.; Lee, S.Y.; Youn, J.C.; Chung, W.B.; Jung, H.O.; Youn, H.J. Associations Between Fasting Glucose and Cardiovascular Disease Mortality in Cancer Survivors: A Population-based Cohort Study. Cardiometab Syndr. J. 2024, 4, 9–19. [Google Scholar]
- Jung, M.H.; Ihm, S.H. Improving the Quality of Hypertension Management: Multifaceted Approach. Korean Circ. J. 2019, 49, 528–531. [Google Scholar]
- Jung, M.H.; Choi, Y.S.; Yi, S.W.; An, S.J.; Yi, J.J.; Ihm, S.H.; Lee, S.Y.; Youn, J.C.; Chung, W.B.; Jung, H.O.; et al. Socioeconomic status and cardiovascular mortality in over 170,000 cancer survivors. Eur. Heart J. Qual. Care Clin. Outcomes 2024, qcae055. [Google Scholar] [CrossRef]
Variable | Total, n | Good Adherence | Moderate Adherence | Poor Adherence | |
---|---|---|---|---|---|
Participants | Number | 7928 | 3197 (40.3%) | 1753 (22.1%) | 2978 (37.6%) |
Sex | Male | 5382 | 2112 (39.2%) | 1202 (22.3%) | 2068 (38.4%) |
Female | 2546 | 1085 (42.6%) | 551 (21.6%) | 910 (35.7%) | |
Age group, years | 20–39 | 263 | 66 (25.1%) | 50 (19.0%) | 147 (55.9%) |
40–59 | 2977 | 1182 (39.7%) | 677 (22.7%) | 1118 (37.6%) | |
60–84 | 4688 | 1949 (41.6%) | 1026 (21.9%) | 1713 (36.5%) | |
Residential area | Seoul | 1679 | 712 (42.4%) | 338 (20.1%) | 629 (37.5%) |
Urban | 1963 | 780 (39.7%) | 433 (22.1%) | 750 (38.2%) | |
Suburb | 4286 | 1705 (39.8%) | 982 (22.9%) | 1599 (37.3%) | |
Income level | ≤30% (low) | 1516 | 583 (38.5%) | 347 (22.9%) | 586 (38.7%) |
31–60% | 1911 | 750 (39.2%) | 436 (22.8%) | 725 (37.9%) | |
61–90% | 2975 | 1207 (40.6%) | 639 (21.5%) | 1129 (37.9%) | |
91–100% (high) | 1526 | 657 (43.1%) | 331 (21.7%) | 538 (35.3%) | |
Prevalence of cancer | Breast cancer | 279 | 153 (54.8%) | 54 (19.4%) | 72 (25.8%) |
Non-Hodgkin’s disease | 58 | 24 (41.4%) | 16 (27.6%) | 18 (31.0%) | |
Gastric cancer | 1137 | 417 (36.7%) | 245 (21.5%) | 475 (41.8%) | |
Colon cancer | 1322 | 559 (42.3%) | 290 (21.9%) | 473 (35.8%) | |
Lung cancer | 1049 | 417 (39.8%) | 227 (21.6%) | 403 (38.4%) | |
Renal cell carcinoma | 152 | 63 (41.4%) | 36 (23.7%) | 53 (34.8%) | |
Liver cancer | 2018 | 705 (34.9%) | 470 (23.3%) | 843 (41.8%) | |
Gallbladder cancer | 104 | 50 (48.1%) | 21 (20.2%) | 33 (31.7%) | |
Ovarian cancer | 179 | 68 (38.0%) | 43 (24.0%) | 68 (38.0%) | |
Prostate cancer | 1630 | 739 (45.3%) | 351 (21.5%) | 540 (33.1%) | |
Previous medical history a | Any CVD | 4047 | 1678 (41.7%) | 959 (23.7%) | 1410 (34.8%) |
IHD | 2358 | 1010 (42.8%) | 567 (24.0%) | 781 (33.1%) | |
PAD | 2174 | 926 (42.6%) | 504 (23.2%) | 744 (34.2%) | |
CVA | 1473 | 588 (39.9%) | 356 (24.2%) | 529 (35.9%) | |
HF | 834 | 297 (35.6%) | 198 (23.7%) | 339 (40.6%) | |
CKD | 271 | 73 (26.9%) | 58 (21.4%) | 140 (51.7%) | |
Previous admission history b | Any CVD | 1210 | 465 (38.4%) | 272 (22.5%) | 473 (39.1%) |
IHD | 762 | 294 (38.6%) | 173 (22.7%) | 295 (38.7%) | |
PAD | 208 | 76 (36.5%) | 43 (20.7%) | 89 (42.8%) | |
CVA | 484 | 164 (33.9%) | 117 (24.2%) | 203 (41.9%) | |
HF | 215 | 69 (32.1%) | 48 (22.3%) | 98 (45.6%) | |
CKD | 122 | 18 (14.8%) | 25 (20.5%) | 79 (64.8%) | |
Anti-diabetic medication | AGI | 1623 | 866 (53.4%) | 460 (28.3%) | 297 (18.3%) |
SU | 3884 | 1850 (47.6%) | 1094 (28.2%) | 940 (24.2%) | |
GLP-1 | - | - (0.0%) | - (0.0%) | - (0.0%) | |
DPP4I | 235 | 144 (44.3%) | 66 (28.1%) | 25 (10.6%) | |
INSULIN | 1505 | 539 (35.8%) | 413 (27.4%) | 553 (35.4%) | |
MET | 3280 | 1653 (49.8%) | 894 (27.3%) | 733 (22.3%) | |
GLN | 428 | 210 (49.1%) | 141 (32.9%) | 77 (18.0%) | |
TZD | 821 | 453 (53.0%) | 235 (28.6%) | 133 (16.2%) | |
Status of diabetes | Pre-existing | 4564 | 2032 (44.5%) | 1213 (26.6%) | 1319 (28.9%) |
Newly diagnosed | 3364 | 1165 (34.6%) | 540 (16.1%) | 1659 (49.3%) |
Outcome | Group | No. of Events | Crude | Multivariable Adjusted * | ||
---|---|---|---|---|---|---|
HR (95% CI) | p Value | HR (95% CI) | p Value | |||
All-cause mortality | Good | 369 | 1.00 (reference) | - | 1.00 (reference) | - |
Moderate | 339 | 1.72 (1.49–2.00) | <0.001 | 1.70 (1.47–1.98) | <0.001 | |
Poor | 754 | 2.28 (2.01–2.58) | <0.001 | 2.11 (1.86–2.40) | <0.001 | |
CV mortality | Good | 51 | 1.00 (reference) | - | 1.00 (reference) | - |
Moderate | 43 | 1.58 (1.06–2.38) | 0.027 | 1.51 (1.01–2.27) | 0.046 | |
Poor | 108 | 2.37 (1.70–3.31) | <0.001 | 2.10 (1.50–2.95) | <0.001 |
Outcome | Group | No. of Events | Crude | Multivariable Adjusted * | ||
---|---|---|---|---|---|---|
HR (95% CI) | p Value | HR (95% CI) | p Value | |||
New-onset any CVD | Good | 998 | 1.00 (reference) | - | 1.00 (reference) | - |
Moderate | 678 | 1.32 (1.20–1.45) | <0.001 | 1.32 (1.19–1.45) | <0.001 | |
Poor | 1221 | 1.43 (1.31–1.55) | <0.001 | 1.44 (1.32–1.56) | <0.001 | |
New-onset IHD | Good | 662 | 1.00 (reference) | - | 1.00 (reference) | - |
Moderate | 448 | 1.29 (1.14–1.45) | <0.001 | 1.28 (1.14–1.44) | <0.001 | |
Poor | 802 | 1.37 (1.24–1.52) | <0.001 | 1.40 (1.26–1.55) | <0.001 | |
New-onset PAD | Good | 187 | 1.00 (reference) | - | 1.00 (reference) | - |
Moderate | 145 | 1.47 (1.18–1.82) | 0.0005 | 1.41 (1.14–1.75) | 0.0019 | |
Poor | 245 | 1.47 (1.21–1.78) | <0.001 | 1.43 (1.18–1.73) | 0.0003 | |
New-onset CVA | Good | 405 | 1.00 (reference) | - | 1.00 (reference) | - |
Moderate | 288 | 1.34 (1.16–1.56) | 0.0001 | 1.32 (1.13–1.53) | 0.0004 | |
Poor | 544 | 1.55 (1.36–1.76) | <0.001 | 1.51 (1.33–1.72) | <0.001 | |
New-onset HF | Good | 197 | 1.00 (reference) | - | 1.00 (reference) | - |
Moderate | 156 | 1.49 (1.21–1.84) | 0.0002 | 1.44 (1.17–1.78) | 0.0007 | |
Poor | 345 | 1.98 (1.67–2.36) | <0.001 | 1.92 (1.60–2.29) | <0.001 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Jung, M.-H.; Jung, M.-K.; Kim, E.-S.; Youn, J.-C.; Lee, E.Y.; Kang, D.; Kyoung, D.-S.; Chung, W.-B.; Jung, H.O.; Ihm, S.-H.; et al. Adherence to Antidiabetic Medication and Cardiovascular Outcomes in Cancer Patients: A Nationwide Population-Based Cohort Study. Cancers 2025, 17, 1117. https://doi.org/10.3390/cancers17071117
Jung M-H, Jung M-K, Kim E-S, Youn J-C, Lee EY, Kang D, Kyoung D-S, Chung W-B, Jung HO, Ihm S-H, et al. Adherence to Antidiabetic Medication and Cardiovascular Outcomes in Cancer Patients: A Nationwide Population-Based Cohort Study. Cancers. 2025; 17(7):1117. https://doi.org/10.3390/cancers17071117
Chicago/Turabian StyleJung, Mi-Hyang, Moon-Kyung Jung, Eui-Soon Kim, Jong-Chan Youn, Eun Young Lee, Dongwoo Kang, Dae-Sung Kyoung, Woo-Baek Chung, Hae Ok Jung, Sang-Hyun Ihm, and et al. 2025. "Adherence to Antidiabetic Medication and Cardiovascular Outcomes in Cancer Patients: A Nationwide Population-Based Cohort Study" Cancers 17, no. 7: 1117. https://doi.org/10.3390/cancers17071117
APA StyleJung, M.-H., Jung, M.-K., Kim, E.-S., Youn, J.-C., Lee, E. Y., Kang, D., Kyoung, D.-S., Chung, W.-B., Jung, H. O., Ihm, S.-H., Lee, H., Ng, C. T., & Kim, H. C. (2025). Adherence to Antidiabetic Medication and Cardiovascular Outcomes in Cancer Patients: A Nationwide Population-Based Cohort Study. Cancers, 17(7), 1117. https://doi.org/10.3390/cancers17071117