Intracellular Pharmacokinetics of Antidiabetic Drugs: A Focused Narrative Review of Subcellular Distribution (2015–2025)

TL;DR

This review explores how antidiabetic drugs reach specific parts of cells, showing that drug effectiveness depends on where they accumulate inside cells, not just their levels in the blood.

Contribution

The paper provides a comprehensive synthesis of subcellular drug distribution patterns and their clinical relevance for antidiabetic drugs.

Findings

Biguanides accumulate in mitochondria, thiazolidinediones in cell nuclei, and GLP-1 agonists in endosomes.

Transporter genes like OCT1 influence drug delivery to subcellular targets.

Standardized human studies are needed to translate these findings into clinical practice.

Abstract

Background/Objectives: The efficacy of antidiabetic drugs is determined by intracellular target exposure rather than solely by plasma concentrations. This review synthesizes current evidence regarding subcellular drug distribution and its clinical significance. Methods: A structured review of the literature published between 2015 and 2025 identified 73 relevant studies. Data were categorized by drug class, factors influencing distribution, and analytical methodologies. Results: Drug distribution patterns differ by class. Biguanides accumulate in mitochondria, thiazolidinediones localize in cell nuclei, and GLP-1 agonists are found in endosomes. Variations in transporter genes, such as OCT1, influence the extent of drug delivery to these subcellular targets. Conclusions: Investigations into intracellular drug movement elucidate their mechanisms of action. However, standardized human studies are required before these findings can inform clinical practice or regulatory decisions.

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