Liver intertwined with pills and DNA, symbolizing drug metabolism in diabetes.

Diabetes and Drug Metabolism: What You Need to Know

Samir D’Costa in Health & Wellness June 2025 • 4 min read.

"New research highlights how diabetes affects drug metabolism, impacting treatment effectiveness and safety."

Diabetes mellitus (DM), a widespread endocrine disorder characterized by elevated blood glucose levels, affects millions globally. In the Middle East, countries like Jordan and Syria report diabetes prevalence rates of 17.1% and 15.6%, respectively. Beyond its direct impact on blood sugar, diabetes can lead to microvascular and macrovascular damage affecting major organs, including the heart, kidneys, eyes, nerves, and liver.

The liver, a primary site for drug metabolism, is particularly vulnerable in diabetic patients. Uncontrolled diabetes can impair liver function, increasing the risk of liver failure, steatosis, and even cancer. Furthermore, studies suggest that diabetes can alter the liver's capacity to process medications, potentially leading to suboptimal treatment outcomes.

A groundbreaking study investigated how diabetes affects the expression of key drug-metabolizing enzymes in the livers of mice with controlled and uncontrolled insulin-dependent diabetes. The findings shed light on the intricate relationship between diabetes and drug metabolism, offering insights that could improve medication management for individuals with diabetes.

How Does Diabetes Impact Drug Metabolism?

Liver intertwined with pills and DNA, symbolizing drug metabolism in diabetes.

The study revealed significant alterations in the gene expression of cytochrome P450 enzymes (CYP450s), which play a crucial role in drug and arachidonic acid metabolism. These enzymes are essential for breaking down and eliminating drugs from the body. The research compared mice with uncontrolled diabetes (UDM), controlled diabetes (CDM), and a control group to understand these changes.

Key findings from the study include:

Downregulation of CYP450s: Mice with uncontrolled diabetes exhibited a significant downregulation of CYP450 gene expression in the liver. The most affected genes included CYP4A12, CYP1A2, and SLC22A1, with more than a 10-fold reduction.
Impact of Insulin: Controlled diabetic mice treated with insulin showed higher levels of mRNA compared to UDM mice, though still lower than non-diabetic mice, indicating insulin's role in partially restoring enzyme expression.
Arachidonic Acid Metabolism: The study also highlighted reduced expression of enzymes involved in arachidonic acid metabolism, which could affect the metabolism of fatty acids and overall liver health.

These alterations in gene expression can influence how drugs are processed in the body, affecting their effectiveness and potentially increasing the risk of adverse effects. For instance, reduced CYP450 activity may lead to slower drug metabolism, resulting in higher drug concentrations and prolonged exposure.

What Does This Mean for People with Diabetes?

The study underscores the importance of understanding how diabetes affects drug metabolism. Healthcare providers need to consider these factors when prescribing medications to diabetic patients. Monitoring drug levels, adjusting dosages, and being vigilant for potential side effects are crucial steps in ensuring optimal treatment outcomes and patient safety. Further research is needed to fully elucidate the clinical implications of these findings and develop personalized medication strategies for individuals with diabetes.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.2147/dmso.s172664, Alternate LINK

Title: Alterations In The Gene Expression Of Drug And Arachidonic Acid-Metabolizing Cyp450 In The Livers Of Controlled And Uncontrolled Insulin-Dependent Diabetic Mice

Subject: Pharmacology

Journal: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy

Publisher: Informa UK Limited

Authors: Yazun Jarrar, Lauy Al-Essa, Abdulhasib Kilani, Mariam Hasan, Walid Al-Qerem

Published: 2018-09-01

Everything You Need To Know

How does diabetes impact liver function and why is that important for drug metabolism?

Diabetes mellitus, particularly when uncontrolled, can significantly impair liver function. This impairment increases the risk of liver failure, steatosis, and even cancer. Furthermore, diabetes can alter the liver's capacity to process medications, potentially leading to suboptimal treatment outcomes. This is because the liver is a primary site for drug metabolism, and its compromised function directly impacts how drugs are processed.

What significant changes in enzyme expression were observed in the livers of mice with uncontrolled diabetes, according to the study?

The study found that in mice with uncontrolled diabetes, there was a significant downregulation of cytochrome P450 enzymes, specifically CYP4A12, CYP1A2, and SLC22A1. This means that the expression of these genes was reduced, in some cases by more than 10-fold. In controlled diabetic mice treated with insulin, mRNA levels were higher compared to the uncontrolled group but still lower than in non-diabetic mice, indicating partial restoration of enzyme expression through insulin treatment.

Why are cytochrome P450 enzymes (CYP450s) so important and how does diabetes influence their function?

Cytochrome P450 enzymes (CYP450s) are crucial for drug and arachidonic acid metabolism. These enzymes break down and eliminate drugs from the body. When diabetes, especially uncontrolled diabetes, affects the expression of CYP450s, it can lead to slower drug metabolism, resulting in higher drug concentrations and potentially increasing the risk of adverse effects or reducing the drug's effectiveness.

How does diabetes-related reduction in arachidonic acid metabolism affect overall liver health?

The reduced expression of enzymes involved in arachidonic acid metabolism, as seen in the study, could affect the metabolism of fatty acids and overall liver health. Arachidonic acid is involved in various physiological processes, including inflammation and immune responses. Changes in its metabolism could lead to imbalances affecting liver function and potentially contributing to the development of liver diseases like non-alcoholic fatty liver disease (NAFLD). Further research would need to explore these specific links.

What precautions should healthcare providers take when prescribing medications to individuals with diabetes, considering its effect on drug metabolism?

For individuals with diabetes, healthcare providers need to carefully consider how diabetes affects drug metabolism when prescribing medications. This includes monitoring drug levels, adjusting dosages based on individual patient responses, and being vigilant for potential side effects. Personalized medication strategies are essential, especially given the variability in how diabetes can affect drug metabolism. Further research is needed to develop more tailored approaches for medication management in people with diabetes.