6 minutes read time
Hypoglycaemia, a condition in which blood glucose concentration falls below 70 mg/dL (3.9 mmol/L) [1], remains a clinically important concern for patients with Type 2 diabetes (T2DM), particularly when multiple comorbidities necessitate polypharmacy – the concurrent use of five or more medications. A 2022 systematic review reported a pooled prevalence of polypharmacy of approximately 64% among older adults with T2DM [2]. Moreover, a cohort study found that multimorbidity and polypharmacy significantly increased the likelihood of severe hypoglycaemia among individuals receiving glucose-lowering therapy [3].
This article outlines some of the key contributors to hypoglycaemia risk within polypharmacy and highlights how MIMS Clinical Decision Solutions (CDS) supports safer, more informed prescribing in this context.
Comorbidities Leading to Polypharmacy in T2DM
Patients with T2DM frequently present with multiple comorbidities including cardiovascular, renal, respiratory and other metabolic diseases [2]. Pharmacotherapies used to manage these conditions may independently lower blood glucose or potentiate the effects of antidiabetic agents, thereby increasing the risk of hypoglycaemia.
Beta blockers
Beta blockers may impair hepatic glucose production and mask adrenergic symptoms of hypoglycaemia. When used concomitantly with insulin or sulfonylureas, this can elevate the risk of severe or unrecognised hypoglycaemia [4][5].
ACE inhibitors
ACE inhibitors may potentiate the hypoglycaemic effects of insulin and sulfonylureas by increasing insulin sensitivity. In a nested case-control study, ACE inhibitor use was associated with higher rates of hospital admission due to severe hypoglycaemia in diabetic patients [4][5].
Clarithromycin
Clarithromycin, a potent CYP3A4 inhibitor, can significantly increase the plasma concentrations of repaglinide by inhibiting its CYP3A4-mediated metabolism, thereby increasing the risk of hypoglycaemia [5].
Hydroxychloroquine
Although uncommon, hydroxychloroquine has been associated with severe hypoglycaemia through effects on insulin metabolism. Cases have been documented in patients both with and without diabetes, emphasising the need for careful monitoring when combined with glucose-lowering therapies [6].
Monoamine oxidase inhibitors (MAOIs)
Rare reports indicate that MAOIs may induce hypoglycaemia, especially at higher doses. The mechanism may involve stimulation of insulin release due to the presence of the hydrazine group in these agents [4].
Taken together, these examples demonstrate how pharmacological management of common comorbidities can unintentionally increase hypoglycaemia risk through pharmacodynamic and pharmacokinetic effects. Regular medication review and close monitoring are therefore essential in patients with polypharmacy..
Other Risk Factors for Hypoglycaemia
Several patient groups with T2DM that may be at increased risk of hypoglycaemia include:
- Older adults [1]
- Chronic or end-stage kidney disease [1]
- Cognitive impairment or dementia [1]
- Poor or irregular oral intake [1]
- Recent hypoglycaemia (within the past 3 to 6 months) [1]
These risk factors frequently coexist with polypharmacy, further amplifying hypoglycaemia risk.
Impact of Hypoglycaemia in Type 2 Diabetes
Severe hypoglycaemia carries substantial acute and long-term consequences. Acutely, hypoglycaemic episodes are associated with an increased risk of falls, injuries, and hospitalisation, with older adults experiencing disproportionate harm due to frailty and comorbidity burden [1][2].
Beyond immediate safety concerns, recurrent or severe hypoglycaemia has been linked to accelerated cognitive decline in people with diabetes. This evidence underscores the importance of proactive risk identification and careful glycaemic management to minimise both short-term harm and long-term neurological sequelae [1].
Recognising Signs and Symptoms of Hypoglycaemia
Prescribers should ensure that patients and caregivers are educated to recognise common adrenergic and neuroglycopenic symptoms, which may vary with age and comorbidity burden [1]:
- Tremors
- Sweating or chills
- Tachycardia
- Intense hunger
- Dizziness or light-headedness
Early recognition is critical to prompt intervention and prevention of progression to severe hypoglycaemia, particularly in patients exposed to polypharmacy or complex treatment regimens.
- Regular medication review to identify potential high-risk combinations linked to severe hypoglycaemia.
- Deprescribing where appropriate to reduce overall treatment complexity.
- Careful medication selection, when initiating or modifying therapies with known hypoglycaemic interactions.
- Patient education on symptoms of hypoglycaemia, proper medication administration, and dietary consistency.
- Regular blood glucose monitoring particularly following medication changes.
How Does MIMS CDS Help?
MIMS CDS equips prescribers with real-time decision support to reduce the risk of hypoglycaemia in patients receiving polypharmacy.
The Drug Interaction Alert module detects clinically significant drug–drug interactions, including those that may potentiate glucose‑lowering effects, and provides actionable recommendations for monitoring and management of affected regimens.
The Drug Health Alert module helps to minimise risks of polypharmacy in patients with T2DM by identifying medications that may potentially decrease blood glucose levels and providing actionable recommendations for monitoring or modifying therapy.
Together, these modules support informed clinical decision-making, reduce the risk of drug-induced hypoglycaemia and improve patient safety.
Conclusion
Hypoglycaemia in Type 2 diabetes becomes increasingly challenging to manage as treatment complexity rises. Evidence indicates that polypharmacy increases the risk of hypoglycaemia, particularly in those with multimorbidity. By identifying agents that potentiate glucose‑lowering effects and recognising high‑risk patients, prescribers can take proactive steps to prevent avoidable harm.
MIMS CDS provides timely, actionable recommendations at the point of prescribing. Through its Drug Interaction and Drug Health Alert modules, MIMS CDS helps clinicians navigate complex regimens safely and consistently, improving outcomes and reducing medication-related hypoglycaemia risks in patients with T2DM.
References
- American Diabetes Association Professional Practice Committee. 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes-2025. Diabetes Care. 2025 Jan 1;48(1 Suppl 1):S128-S145. See more
- 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. See more
- Koto R, Nakajima A, Miwa T, et al. Multimorbidity, Polypharmacy, Severe Hypoglycemia, and Glycemic Control in Patients Using Glucose-Lowering Drugs for Type 2 Diabetes: A Retrospective Cohort Study Using Health Insurance Claims in Japan. Diabetes Ther. 2023;14(7):1175–1192. See more
- Ben Salem C, Fathallah N, Hmouda H, et al. Drug-induced hypoglycaemia: an update. Drug Saf. 2011 Jan 1;34(1):21-45. See more
- Scheen AJ. Drug interactions of clinical importance with antihyperglycaemic agents: an update. Drug Saf. 2005;28(7):601-31. See more
- McKnight M, Cutshall BT, Sakaan S, Al Hommos NA, Wells DA. Hydroxychloroquine-Induced Hypoglycemia in a Patient Without Diabetes. J Pharm Pract. 2024;37(5):1205–1208. See more