Does diabetes mellitus (DM) affect drug absorption or metabolism?

From the Guidelines

Diabetes mellitus significantly affects both drug absorption and metabolism, necessitating careful consideration and potential dosage adjustments for patients with this condition. The impact of diabetes on drug absorption is multifaceted, including delayed gastric emptying (gastroparesis) which alters the rate at which oral medications enter the small intestine for absorption 1. This effect is particularly relevant for medications where timing of absorption affects efficacy, such as metformin and certain antibiotics.

Regarding drug metabolism, diabetes causes changes in liver enzyme activity, particularly the cytochrome P450 system, which metabolizes many medications. Insulin resistance and hyperglycemia can upregulate some enzymes while downregulating others, leading to unpredictable drug metabolism. Furthermore, diabetes-related kidney disease can reduce drug clearance, potentially causing accumulation of medications like metformin and many antibiotics. Protein glycation in diabetes also affects drug binding to plasma proteins, altering the amount of free (active) drug in circulation.

Key factors to consider in the management of diabetic patients include:

• Monitoring for potential interactions between diabetes medications and other drugs, such as glucocorticoids, statins, and certain antipsychotic medications, which can increase the risk of developing diabetes or exacerbating existing diabetes 1.
• Regular blood glucose monitoring when starting new medications in diabetic patients, as these pharmacokinetic changes can lead to unexpected drug responses.
• Potential dosage adjustments for medications that are affected by the physiological changes associated with diabetes, especially for those with long-standing disease or complications.

From the FDA Drug Label

Metabolism Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. Adults with type 2 diabetes mellitus: 850 mg single dose (23) 1.48 (±0.5) 3.32 (±1.08) 491 (±138) Gender Metformin pharmacokinetic parameters did not differ significantly between normal subjects and patients with type 2 diabetes mellitus when analyzed according to gender (males=19, females=16).

Diabetes Mellitus (DM) Effect on Drug Absorption or Metabolism:

• The provided drug label does not indicate that diabetes mellitus (DM) affects the metabolism of metformin, as metformin is not metabolized in the liver.
• The label shows that metformin absorption is not significantly different between normal subjects and patients with type 2 diabetes mellitus.
• However, the label does indicate that renal function affects metformin elimination, and patients with decreased renal function may have a prolonged plasma and blood half-life of metformin.
• Since diabetes can affect renal function, it may indirectly affect metformin elimination, but not its absorption or metabolism 2.

From the Research

Effect of Diabetes on Drug Absorption

• Diabetes mellitus (DM) may affect drug absorption, although the impact is variable and depends on several factors, including the type of drug and the severity of the disease 3.
• For most drugs that cross the gastrointestinal wall by passive diffusion, oral absorption is unlikely to be affected by diabetes, but some studies have reported delays or decreases in absorption for specific drugs, such as tolazamide and ampicillin 3.
• Subcutaneous absorption of insulin is more rapid in diabetic patients, while intramuscular absorption of other drugs may be slower 3.

Effect of Diabetes on Drug Metabolism

• The metabolic clearance of most drugs in humans appears to be unaffected or slightly reduced by diabetes, although some studies suggest that the presence of fatty liver in non-insulin-dependent diabetes mellitus (NIDDM) may contribute to reduced hepatic clearance 3.
• Diabetes can affect the binding of drugs in the blood, which may lead to changes in drug distribution and clearance 3, 4.
• The regulation of enzymes and transporters involved in drug biotransformation may be altered in diabetes, leading to changes in drug metabolism 4.

Impact of Diabetes on Drug Disposition

• Diabetes can affect drug disposition by altering absorption, distribution, biotransformation, and excretion 4.
• The effects of diabetes on drug disposition are highly variable and depend on the specific drug, the type and severity of the disease, and other factors such as renal function and medication use 4, 5.
• Further clinical studies are needed to understand the clinical significance of the effects of diabetes on drug disposition and to improve the medical management of patients with diabetes 4.