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Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder characterised by chronic hyperglycaemia resulting from a combination of insulin resistance and impaired insulin secretion. Management of T2DM commonly involves lifestyle interventions and pharmacotherapy tailored to maintain glycaemic control and reduce long-term complications.
However, many individuals with T2DM also suffer from additional chronic conditions that require pharmacological treatment, leading to polypharmacy—typically defined as the use of five or more medications concurrently. This is not uncommon in patients with T2DM, particularly older adults. A 2022 systematic review reported a pooled prevalence of polypharmacy of approximately 64% among older adults with T2DM, with associations noted between polypharmacy, poor glycaemic control, and adverse health outcomes [1].
These findings are consistent with longitudinal data from Denmark, where the average number of medications prescribed to individuals with T2DM significantly increased between 2000 and 2020 [2]. Such trends raise important concerns about the clinical risks associated with polypharmacy, especially in relation to glycaemic control.
Comorbidities leading to polypharmacy in T2DM
T2DM patients often have multiple comorbidities such as cardiovascular, renal and other metabolic diseases, which increase the risk of polypharmacy [1].
A large-scale observational study further highlighted the prevalence of comorbidities contributing to increased treatment complexity in T2DM patients, specifically mental health conditions such as depression, anxiety, and schizophrenia [3]. These treatments risk the occurrence of polypharmacy. This also extends to comorbidities including autoimmune disease, hypertension, and chronic kidney disease.
The use of multiple medications increases the likelihood of drug-drug and drug-disease interactions that can impair glycaemic control. According to a systematic review and investigative studies, certain drug regimens in polypharmacy settings may contribute to poor glycaemic control and higher risk of complications in T2DM patients [1][5].
Several commonly prescribed medications are known to increase blood glucose levels through various mechanisms. For instance, glucocorticoids can induce insulin resistance and promote hepatic gluconeogenesis, leading to elevated glucose levels. Atypical antipsychotics such as olanzapine and quetiapine interfere with insulin sensitivity and pancreatic beta-cell function. Protease inhibitors, used in HIV treatment, may impair glucose uptake and cause insulin resistance. Additionally, thiazide diuretics can reduce insulin secretion and increase peripheral insulin resistance. These drug-induced effects complicate glycaemic management in patients with type 2 diabetes, highlighting the importance of careful medication review and monitoring [6].
Consequences of Unchecked Polypharmacy
In people with T2DM, polypharmacy can contribute to increased risk of acute complications, such as drug-induced hyperglycaemia [1]. Complex regimens may impair adherence or lead to inconsistent dosing, both of which can precipitate dangerous metabolic decompensation.
Additionally, polypharmacy may result in drug interactions and adverse effects which may reduce the hypoglycaemic response of antidiabetic agents. This may cause prescribers to increase the dose or introduce more potent agents, increasing the pill burden and the likelihood of adverse outcomes. Over time, such intensification contributes to a cycle of rising medication use without corresponding improvements in glycaemic control.
These trends call for more vigilant medication review and deprescribing where appropriate, especially in those with unstable diabetes.
Solutions: Medication Review and Clinical Support Tools
The literature consistently recommends regular medication reviews as a strategy to reduce polypharmacy-related risks. Deprescribing and careful medication selection have been identified as necessary approaches to improve safety in T2DM patients [1][4]. However, performing effective medication reviews requires access to up-to-date, patient-specific drug interaction data. Moreover, regular monitoring for blood glucose, as well as signs and symptoms of hyperglycaemia, provides a proactive measure to keep patients safe.
Signs and symptoms of hyperglycaemia:
- Increased thirst and hunger
- Frequent urination
- Blurred vision
- Fatigue and tiredness
This is where MIMS Clinical Decision Solutions (MIMS CDS) offers essential support for healthcare professionals.
1. Drug Interaction Alert Module
The Drug Interaction Alert module in MIMS CDS helps prescribers proactively identify and manage clinically significant drug-drug interactions. In the context of T2DM, this is especially valuable given the high prevalence of polypharmacy and the potential for medications to affect glycaemic control indirectly or directly. The module provides:
- Alerts on interactions that may impair antidiabetic therapy effects
- Recommendations on dose adjustments or enhanced monitoring
2. Drug Health Alert Module
The Drug Health Alert module flags medications that may worsen clinical conditions, such as T2DM. It can identify drugs known to affect glycaemic control, which may not present as direct drug-drug interactions but still pose significant risks. The module includes:
- Alerts when prescribing medications associated with poor glycaemic outcomes
- Clinical recommendations for monitoring or modifying therapy
Together, these modules support safer prescribing by helping healthcare professionals make informed decisions in real time, reducing the likelihood of drug-induced hyperglycaemia and minimising the risk of unnecessary therapy escalation.
Conclusion
Polypharmacy in patients with T2DM is both common and clinically significant. Evidence from multiple studies shows a clear link between increased medication use and poorer glycaemic outcomes, particularly in older adults and those with multimorbidity. The risk of drug-drug interactions and inappropriate prescribing further complicates patient management and contributes to adverse events such as hyperglycaemia.
To address these risks, prescribers must adopt a structured approach to medication management, supported by robust clinical decision tools. MIMS Clinical Decision Solutions – through its Drug Interaction and Drug Health Alert modules – provides an integrated platform to identify and mitigate medication-related risks, ensuring safer and more effective care for patients with T2DM.
References
- Remelli F, Ceresini MG, Trevisan C, et al. Prevalence and impact of polypharmacy in older patients with type 2 diabetes. Aging Clin Exp Res. 2022 Sep;34(9):1969-1983.
- Johansson KS, Jimenez‑Solem E, Petersen TS, et al. Increasing Medication Use and Polypharmacy in Type 2 Diabetes: The Danish Experience From 2000 to 2020. Diabetes Care. 2024 Dec 1;47(12):2120‑2127.
- Guerrero Fernández de Alba I, Gimeno-Miguel A, Poblador-Plou B, et al. Association between mental health comorbidity and health outcomes in type 2 diabetes mellitus patients. Sci Rep. 2020 Nov 11;10(1):19583.
- Lipska KJ, Krumholz H, Soones T, et al. Polypharmacy in the Aging Patient: A Review of Glycemic Control in Older Adults With Type 2 Diabetes. JAMA. 2016 Mar 8;315(10):1034-45.
- Al‑Musawe L, Torre C, Guerreiro JP, 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. Pharmacol Res Perspect. 2020 Aug;8(4):e00621.
- Jain AB, Lai V. Medication-Induced Hyperglycemia and Diabetes Mellitus: A Review of Current Literature and Practical Management Strategies. Diabetes Ther. 2024 Sep;15(9):2001-2025.