What medications are contraindicated in patients with Diabetes Mellitus (DM)?

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From the Guidelines

Thiazolidinediones (TZDs) are contraindicated in patients with Diabetes Mellitus (DM) and heart failure (HF), as they may increase the risk of HF hospitalization due to volume expansion caused by increased renal sodium reabsorption 1. When managing patients with DM, it is crucial to consider the potential impact of various medications on their condition.

  • Medications such as TZDs should be avoided in patients with DM and HF, as they can worsen heart failure symptoms and increase the risk of hospitalization.
  • Other medications like DPP-4 inhibitors and sulfonylureas should be used with caution in patients with DM and HF, as they may also increase the risk of HF hospitalization 1.
  • In patients with DM and severe kidney impairment (eGFR <30 mL·min−1·1.73 m−2), metformin should not be used, and SGLT-2 inhibitors should be used with caution, as their safety and efficacy in this population are still being studied 1.
  • The use of GLP-1 receptor agonists in patients with DM and recent HF decompensation should be avoided, as they may increase the risk of HF hospitalization 1.
  • The 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases recommend the use of empagliflozin, canagliflozin, or dapagliflozin in patients with T2DM and CVD, or at very high/high CV risk, to reduce CV events, but do not provide specific guidance on medications to avoid in patients with DM 1.
  • However, the study by 1 provides more specific guidance on medications to avoid in patients with DM and HF, and is therefore considered the most relevant and up-to-date evidence for this question.

From the FDA Drug Label

4 CONTRAINDICATIONS Metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m2) [see Warnings and Precautions (5.1)]. Hypersensitivity to metformin. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.

The medications that are contraindicated in patients with Diabetes Mellitus (DM) are not directly listed, but metformin is contraindicated in patients with:

  • Severe renal impairment
  • Hypersensitivity to metformin
  • Acute or chronic metabolic acidosis, including diabetic ketoacidosis 2

From the Research

Medications Contraindicated in Patients with Diabetes Mellitus (DM)

  • Dual peroxisome-proliferator-activated receptor agonists and sulfonylurea are known to worsen cardiovascular disease in patients with DM, increasing heart failure readmission rates and risk for cardiovascular death 3
  • Thiazolidinediones are relatively contraindicated in patients with New York Heart Association class III or IV disease due to concerns of fluid retention and heart failure exacerbation 4
  • Beta-blockers can increase insulin resistance and are not recommended as first-line drugs for blood pressure lowering indications in subjects at high risk to develop diabetes, especially in patients with metabolic syndrome 5, 6
  • Thiazides can impair glucose tolerance, increase low-density lipoprotein cholesterol, and decrease potassium, making them a less preferred option for patients with DM 5, 6
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) should be used with caution in patients with DM due to their cardiovascular, renal, and gastrointestinal risks 7
  • St. John's wort is a concern for patients with DM due to potential drug interactions 7

Medications to be Used with Caution in Patients with DM

  • Sulfonylureas may not be associated with an increased mortality or deleterious effects on heart failure, but their use should be carefully considered in patients with DM 4
  • Dipeptidylpeptidase 4 inhibitors show an overall neutral outcome, but saxagliptin may be associated with an increased risk of hospitalization for heart failure 4
  • Decongestants, particularly oral ones, may have an impact on blood sugar levels in patients with DM 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Type 2 Diabetes Medication and Cardiovascular Benefits.

South Dakota medicine : the journal of the South Dakota State Medical Association, 2021

Research

Requirements for antihypertensive therapy in diabetic patients: metabolic aspects.

Journal of hypertension. Supplement : official journal of the International Society of Hypertension, 1997

Research

Over-the-Counter Medicines and Diabetes Care.

Canadian journal of diabetes, 2017

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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