Polypharmacy in Type 2 Diabetes Mellitus and Related Conditions: A Double-Edged Sword: A Narrative Review
DOI:
https://doi.org/10.63623/sr9fb890Keywords:
Polypharmacy, Type 2 diabetes mellitus, Metabolic syndrome, MASLD, DeprescribingAbstract
Type 2 diabetes mellitus (T2DM) is a multifaceted metabolic disease that is often associated with comorbidities like cardiovascular disease, hypertension, and dyslipidemia. Managing these coexisting conditions often requires the concurrent use of multiple medications, leading to polypharmacy. Polypharmacy is defined as the use of five or more drugs by the patient. While polypharmacy can be clinically appropriate, it also raises the risk of adverse drug events, therapeutic duplication, poor adherence, and increased healthcare burden. Polypharmacy affects 50-80% of patients with T2DM, especially in older adults. It is associated with increased risks of hypoglycemia, hospitalization, drug–drug interactions, and decreased adherence to antidiabetic therapies. The presence of polypharmacy may compromise glycemic control and is linked to higher rates of diabetes-related complications and mortality. On the other hand, appropriate polypharmacy, based on guideline-directed care, can improve cardiovascular and renal outcomes when carefully managed. Polypharmacy in T2DM represents a clinical challenge that requires a balance between comprehensive disease management and the minimization of iatrogenic harm. Individualized care, regular medication reviews, and deprescribing strategies are essential to optimize therapeutic outcomes in this high-risk population. This review seeks to examine the prevalence, underlying causes, clinical consequences, and management approaches of polypharmacy in individuals with T2DM, with a focus on its impact on glycemic control, treatment safety, and associated outcomes.
References
[1]Vianini E, Pandey A, Rolland C, Ngubane N, Mueller-Wieland D, Gilbert J, et al. Systematic literature review of the impact of type 2 diabetes and heart failure guideline adherence on clinical and economic outcomes. Diabetes Therapy, 2025, 16(12), 851-864. DOI: 10.1007/s13300-025-01725-8
[2]Ferdous SE, Ferrell JM. Pathophysiological relationship between type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease: Novel therapeutic approaches. International Journal of Molecular Sciences, 2024, 25(16), 8731. DOI: 10.3390/ijms25168731
[3]Lu X, Xie Q, Pan X, Zhang R, Zhang X, Peng G, et al. Type 2 diabetes mellitus in adults: Pathogenesis, prevention and therapy. Signal Transduction and Targeted Therapy, 2024, 9(1), 262. DOI: 10.1038/s41392-024-01951-9
[4]Iwasaki H, Yagyu H, Shimano H. A comprehensive analysis of diabetic complications and advances in management strategies. Journal of Atherosclerosis and Thrombosis, 2025, 32(5), 550-559. DOI: 10.5551/jat.65551
[5]Alobaid T, Karalliedde J, O'Connell MD, Gnudi L, Sheehan K, Lim KK, et al. The prevalence and progression of microvascular complications and the interaction with ethnicity and socioeconomic status in people with type 2 diabetes: A systematic review and meta-analysis. Journal of Diabetes Research, 2025, 2025, 3307594. DOI: 10.1155/jdr/3307594
[6]Iradukunda A, Kembabazi S, Ssewante N, Kazibwe A, Kabakambira JD. Diabetic complications and associated factors: A 5-year facility-based retrospective study at a tertiary hospital in Rwanda. Diabetes, Metabolic Syndrome and Obesity, 2021, 14, 4801-4810. DOI: 10.2147/dmso.s343974
[7]Pazan F, Wehling M. Polypharmacy in older adults: A narrative review of definitions, epidemiology and consequences. European Geriatric Medicine, 2021, 12(3), 443-452. DOI: 10.1007/s41999-021-00479-3
[8]Varghese D, Ishida C, Patel P, Haseer Koya H. Polypharmacy. StatPearls. 2025.
[9]Atak BM, Aktas G, Duman TT, Kurtkulagi O, Bilgin S, Kahveci G, et al. Inappropriate medication use in older adults according to beers criteria in a tertiary referral hospital, in Bolu, Turkey. Russian Open Medical Journal, 2021, 10(2), 211. DOI: 10.15275/rusomj.2021.0211
[10]Kochar B, Rusher A, Araka E, Glasser R, Lai J, Ritchie C, et al. Prevalence and appropriateness of polypharmacy in older adults with inflammatory bowel diseases. Digestive Diseases and Sciences, 2024, 69(3), 766-774. DOI: 10.1007/s10620-023-08250-3
[11]Delara M, Murray L, Jafari B, Bahji A, Goodarzi Z, Kirkham J, et al. Prevalence and factors associated with polypharmacy: A systematic review and meta-analysis. BMC Geriatrics, 2022, 22(1), 601. DOI: 10.1186/s12877-022-03279-x
[12]Poudel A, Peel NM, Nissen LM, Mitchell CA, Gray LC, Hubbard RE. Adverse outcomes in relation to polypharmacy in robust and frail older hospital patients. Journal of the American Medical Directors Association, 2016, 17(8), 767.e769-767.e713. DOI: 10.1016/j.jamda.2016.05.017
[13]Chen N, Alam AB, Lutsey PL, MacLehose RF, Claxton JS, Chen LY, et al. Polypharmacy, adverse outcomes, and treatment effectiveness in patients ≥75 with atrial fibrillation. Journal of the American Heart Association, 2020, 9(11), e015089. DOI: 10.1161/jaha.119.015089
[14]Mohamed MR, Ramsdale E, Loh KP, Arastu A, Xu H, Obrecht S, et al. Associations of polypharmacy and inappropriate medications with adverse outcomes in older adults with cancer: A systematic review and meta-analysis. Oncologist, 2020, 25(1), e94-e108. DOI: 10.1634/theoncologist.2019-0406
[15]Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opinion on Drug Safety, 2014, 13(1), 57-65. DOI: 10.1517/14740338.2013.827660
[16]Gellad WF, Grenard JL, Marcum ZA. A systematic review of barriers to medication adherence in the elderly: Looking beyond cost and regimen complexity. American Journal of Geriatric Pharmacotherapy, 2011, 9(1), 11-23. DOI: 10.1016/j.amjopharm.2011.02.004
[17]Whitty JA, Stewart S, Carrington MJ, Calderone A, Marwick T, Horowitz JD, et al. Patient preferences and willingness-to-pay for a home or clinic based program of chronic heart failure management: Findings from the which? Trial. PLoS One, 2013, 8(3), e58347. DOI: 10.1371/journal.pone.0058347
[18]Atak Tel BM, Aktas G, Bilgin S, Baltaci SB, Taslamacioglu Duman T. Control level of type 2 diabetes mellitus in the elderly is associated with polypharmacy, accompanied comorbidities, and various increased risks according to the beers criteria. Diagnostics (Basel), 2023, 13(22). DOI: 10.3390/diagnostics13223433
[19]By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated Ags Beers Criteria® for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society, 2023, 71(7), 2052-2081. DOI: 10.1111/jgs.18372
[20]O'Mahony D, O'Sullivan D, Byrne S, O'Connor MN, Ryan C, Gallagher P. STOPP/START criteria for potentially inappropriate prescribing in older people: Version 2. Age Ageing, 2015, 44(2), 213-218. DOI: 10.1093/ageing/afu145
[21]Scott IA, Hilmer SN, Reeve E, Potter K, Le Couteur D, Rigby D, et al. Reducing inappropriate polypharmacy: The process of deprescribing. JAMA Internal Medicine, 2015, 175(5), 827-834. DOI: 10.1001/jamainternmed.2015.0324
[22]9. Pharmacologic approaches to glycemic treatment: Standards of care in diabetes-2024. Diabetes Care, 2024, 47(Supplement 1), S158-s178. DOI: 10.2337/dc24-S009
[23]Khezrian M, McNeil CJ, Murray AD, Myint PK. An overview of prevalence, determinants and health outcomes of polypharmacy. Therapeutic Advances in Drug Safety, 2020, 11, 2042098620933741. DOI: 10.1177/2042098620933741
[24]Bosworth HB, Fortmann SP, Kuntz J, Zullig LL, Mendys P, Safford M, et al. Recommendations for providers on person-centered approaches to assess and improve medication adherence. Journal of General Internal Medicine, 2017, 32(1), 93-100. DOI: 10.1007/s11606-016-3851-7
[25]Jyrkkä J, Enlund H, Lavikainen P, Sulkava R, Hartikainen S. Association of polypharmacy with nutritional status, functional ability and cognitive capacity over a three-year period in an elderly population. Pharmacoepidemiology and Drug Safety, 2011, 20(5), 514-522. DOI: 10.1002/pds.2116
[26]Remelli F, Ceresini MG, Trevisan C, Noale M, Volpato S. Prevalence and impact of polypharmacy in older patients with type 2 diabetes. Aging Clinical and Experimental Research, 2022, 34(9), 1969-1983. DOI: 10.1007/s40520-022-02165-1
[27]Jose JV, Devi P, Satish R. Polypharmacy and predictors of high level polypharmacy in patients with diabetic nephropathy in a tertiary care hospital. International Journal of Basic & Clinical Pharmacology, 2019, 8(6), 1371-1376. DOI: 10.18203/2319-2003.ijbcp20192204
[28]Schneider M, Bandiera C, Dotta-Celio J, Zanchi A. [medication adherence and physician-pharmacist collaboration. Focus on the patient with diabetic nephropathy]. Revue médicale suisse, 2020, 16(697), 1210-1213.
[29]Zhang B, Wang J, Liu N, Liu W, Xi R, Wang P. Association between polypharmacy and chronic kidney disease among community-dwelling older people: A longitudinal study in southern China. BMC Nephrology, 2024, 25(1), 169. DOI: 10.1186/s12882-024-03606-x
[30]Min HK, Sung SA, Chung W, Kim YH, Chae DW, Ahn C, et al. Polypharmacy and the progression of chronic kidney disease: Korean cohort study for outcome in patients with chronic kidney disease. Kidney and Blood Pressure Research, 2021, 46(4), 460-468. DOI: 10.1159/000516029
[31]Good CB. Polypharmacy in elderly patients with diabetes. Diabetes Spectrum, 2002, 15(4), 240-248. DOI: 10.2337/diaspect.15.4.240
[32]Naghnaghia S, Nazzal Z, Abu Alya L, Al-Ramahi R, Hamdan Z, Samara E. The association between renal impairment and polypharmacy among older palestinian patients: A multi-center cross-sectional study. BMC Primary Care, 2023, 24(1), 50. DOI: 10.1186/s12875-023-02005-9
[33]Dobrică EC, Găman MA, Cozma MA, Bratu OG, Pantea Stoian A, Diaconu CC. Polypharmacy in type 2 diabetes mellitus: Insights from an internal medicine department. Medicina (Kaunas), 2019, 55(8). DOI: 10.3390/medicina55080436
[34]Naseralallah L, Khatib M, Al-Khulaifi A, Danjuma M. Prevalence and global trends of polypharmacy in patients with chronic kidney disease: A systematic review and meta-analysis. Frontiers in Pharmacology, 2023, 14, 1122898. DOI: 10.3389/fphar.2023.1122898
[35]Nisa M, Naseralallah L, Altarawneh L, Ally R, Danjuma M. The prevalence of potentially inappropriate medications among patients with diabetic nephropathy: A cross-sectional study conducted at a tertiary care hospital. Cureus, 2024, 16(11), e74159. DOI: 10.7759/cureus.74159
[36]Devi DP, George J. Diabetic nephropathy: Prescription trends in tertiary care. Indian Journal of Pharmaceutical Sciences, 2008, 70(3), 374-378. DOI: 10.4103/0250-474x.43007
[37]Al-Musawe L, Torre C, Guerreiro JP, Rodrigues AT, Raposo JF, Mota-Filipe H, et al. Polypharmacy, potentially serious clinically relevant drug-drug interactions, and inappropriate medicines in elderly people with type 2 diabetes and their impact on quality of life. Pharmacology Research & Perspectives, 2020, 8(4), e00621. DOI: 10.1002/prp2.621
[38]Kumari S, Jain S, Kumar S. Effects of polypharmacy in elderly diabetic patients: A review. Cureus, 2022, 14(9), e29068. DOI: 10.7759/cureus.29068
[39]Wang M, Li M, Xie Y. The association between statins exposure and peripheral neuropathy risk: A meta-analysis. Journal of Clinical Pharmacy and Therapeutics, 2021, 46(4), 1046-1054. DOI: 10.1111/jcpt.13393
[40]Zangiabadi N, Shafiee K, Alavi KH, Assadi AR, Damavandi M. Atorvastatin treatment improves diabetic polyneuropathy electrophysiological changes in non-insulin dependent diabetic patients: A double blind, randomized clinical trial. Minerva Endocrinology, 2012, 37(2), 195-200.
[41]Hernández-Ojeda J, Román-Pintos LM, Rodríguez-Carrízalez AD, Troyo-Sanromán R, Cardona-Muñoz EG, Alatorre-Carranza Mdel P, et al. Effect of rosuvastatin on diabetic polyneuropathy: A randomized, double-blind, placebo-controlled phase IIa study. Diabetes Metabolic Syndrome and Obesity, 2014, 7, 401-407. DOI: 10.2147/dmso.s65500
[42]Daliri M, Johnston TP, Sahebkar A. Statins and peripheral neuropathy in diabetic and non-diabetic cases: A systematic review. Journal of Pharmacy and Pharmacology, 2023, 75(5), 593-611. DOI: 10.1093/jpp/rgac104
[43]Hammad MA, Syed Sulaiman SA, Alghamdi S, Mangi AA, Aziz NA, Mohamed Noor DA. Statins-related peripheral neuropathy among diabetic patients. Diabetology & Metabolic Syndrome, 2020, 14(4), 341-346. DOI: 10.1016/j.dsx.2020.04.005
[44]Wannarong T, Chaikijurajai T, Preston DC, Naweera W, Sukpornchairak P, Ungprasert P. Statins and the risk of polyneuropathy: A systematic review and two meta-analyses. Muscle & Nerve, 2022, 65(1), 120-125. DOI: 10.1002/mus.27447
[45]Alrasheed M, Guo JJ, Lin AC, Wigle PR, Hardee A, Hincapie AL. The effect of polypharmacy on quality of life in adult patients with nonalcoholic fatty liver disease in the United States. Quality of Life Research, 2022, 31(8), 2481-2491. DOI: 10.1007/s11136-022-03090-6
[46]Chávez-López LM, Carballo-López GI, Lugo-Ibarra KDC, Castro-Ceseña AB. A comprehensive framework for managing metabolic dysfunction-associated steatotic liver disease: Analyzing novel risk factors and advances in nanotechnology-based treatments and diagnosis. RSC Medicinal Chemistry, 2024, 15(8), 2622-2642. DOI: 10.1039/d4md00420e
[47]Byrne CD, Targher G. NAFLD: A multisystem disease. Journal of Hepatology, 2015, 62(1 Suppl), S47-64. DOI: 10.1016/j.jhep.2014.12.012
[48]Vrentzos E, Pavlidis G, Korakas E, Kountouri A, Pliouta L, Dimitriadis GD, et al. Nutraceutical strategies for metabolic dysfunction-associated steatotic liver disease (MASLD): A path to liver health. Nutrients, 2025, 17(10), 1657. DOI: 10.3390/nu17101657
[49]Patel PJ, Hayward KL, Rudra R, Horsfall LU, Hossain F, Williams S, et al. Multimorbidity and polypharmacy in diabetic patients with NAFLD: Implications for disease severity and management. Medicine (Baltimore), 2017, 96(26), e6761. DOI: 10.1097/md.0000000000006761
[50]Ramírez-Mejía MM, Teschke R, Méndez-Sánchez N. Open questions on how metabolic dysfunction-associated steatotic liver disease shapes the course of drug-induced liver injury. World Journal of Hepatology, 2025, 17(5), 105072. DOI: 10.4254/wjh.v17.i5.105072
[51]Ali SMJ, Lai M. Metabolic dysfunction-associated steatotic liver disease. Annals of Internal Medicine, 2025, 178(1), ITC1-ITC16. DOI: 10.7326/annals-24-02933
[52]Koullias E, Papavdi M, Koskinas J, Deutsch M, Thanopoulou A. Targeting metabolic dysfunction-associated steatotic liver disease (MASLD): Available and future pharmaceutical options. Cureus, 2025, 17(1), e76716. DOI: 10.7759/cureus.76716
[53]Paik JM, Henry L, Younossi Y, Ong J, Alqahtani S, Younossi ZM. The burden of nonalcoholic fatty liver disease (NAFLD) is rapidly growing in every region of the world from 1990 to 2019. Hepatology Communications, 2023, 7(10). DOI: 10.1097/hc9.0000000000000251
[54]Dong X, Li JM, Lu XL, Lin XY, Hong MZ, Weng S, et al. Global burden of adult non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) has been steadily increasing over the past decades and is expected to persist in the future. Translational Gastroenterology and Hepatology, 2024, 9, 33. DOI: 10.21037/tgh-23-118
[55]Amer J, Abdoh Q, Salous Z, Alsoud EA, AbuBaker S, Salhab A, et al. A cross-sectional study of risk factors associated with sarcopenia in patients with metabolic dysfunction-associated steatotic liver disease. Frontiers in Medicine, 2025, 12, 1488068. DOI: 10.3389/fmed.2025.1488068
[56]Correll CU, Frederickson AM, Kane JM, Manu P. Does antipsychotic polypharmacy increase the risk for metabolic syndrome? Schizophrenia Research, 2007, 89(1-3), 91-100. DOI: 10.1016/j.schres.2006.08.017
[57]Mohsenzadeh P, Ardekani A, Poustchi H, Mohammadi Z, Abdipour Mehrian SR, Bazrafshan Drissi H, et al. Population-based pattern of medication use and prevalence of polypharmacy among patients with cardiovascular diseases: Results of the pars cohort study from Iran. BMC Cardiovascular Disorders, 2022, 22(1), 435. DOI: 10.1186/s12872-022-02872-7
[58]Santos A, Nogueira DRC, Gutierrez BAO, Chubaci RYS, Oliveira CRB. Cardiometabolic diseases and active aging - polypharmacy in control. Revista Brasileira de Enfermagem, 2020, 73(2), e20180324. DOI: 10.1590/0034-7167-2018-0324
[59]Misawa F, Shimizu K, Fujii Y, Miyata R, Koshiishi F, Kobayashi M, et al. Is antipsychotic polypharmacy associated with metabolic syndrome even after adjustment for lifestyle effects?: A cross-sectional study. BMC Psychiatry, 2011, 11, 118. DOI: 10.1186/1471-244x-11-118
[60]Lillich FF, Imig JD, Proschak E. Multi-target approaches in metabolic syndrome. Frontiers in Pharmacology, 2020, 11, 554961. DOI: 10.3389/fphar.2020.554961
[61]Cole JA, Gonçalves-Bradley DC, Alqahtani M, Barry HE, Cadogan C, Rankin A, et al. Interventions to improve the appropriate use of polypharmacy for older people. Cochrane Database of Systematic Reviews, 2023, 10(10), CD008165. DOI: 10.1002/14651858.CD008165.pub5
[62]Aktas G. Association between the prognostic nutritional index and chronic microvascular complications in patients with type 2 diabetes mellitus. Journal of Clinical Medicine, 2023, 12(18), 5952. DOI: 10.3390/jcm12185952
[63]Dedemen B, Duman TT, Dedemen MM, Aktas G. Effect of sodium glucose co-transporter 2 inhibitor use on anthropometric measurements and blood glucose in obese and non-obese type 2 diabetic patients. Clinical Nutrition ESPEN, 2024, 63, 515-519. DOI: 10.1016/j.clnesp.2024.07.016
[64]Basaran E, Aktas G. Waist-to-height ratio as a novel marker of metabolic syndrome in patients with type 2 diabetes mellitus. Exploration of Endocrine and Metabolic Diseases, 2025, 2, 101421. DOI: 10.37349/eemd.2025.101421
[65]Kosekli MA, Aktas G. The systemic immune inflammation index is a reliable and novel risk factor for metabolic dysfunction-associated fatty liver disease. Current Medical Research and Opinion, 2025, 41(2), 247-251. DOI: 10.1080/03007995.2025.2463952
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