Type 2 diabetes mellitus as a state of altered drug pharmacokinetic-pharmacodynamic parameters: an update on recent...

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterised by hyperglycaemia. And its global prevalence is increasing at an alarming rate. Uncontrolled diabetes can progress to an alteration of tissue and organ system morphology and function, resulting in complications that affect drug pharmacokinetics (PKs) and pharmacodynamics (PDs). Diabetes is associated with several physiological changes including delayed gastric emptying, intestinal drug transporters, cytochrome P450, hypoalbuminemia and an increase or decline in glomerular filtration rate. From a PK point of view, these pathophysiological changes in 2 diabetes mellitus could lead to altered drug absorption, distribution, metabolism and clearance. Consequently, such PKs changes can lead to variability in the PD responses of many drugs, increasing the risk of treatment failure or adverse effects. Furthermore, T2DM sensitise individuals to co-morbidities, thus, necessitating polypharmacy, heightening the risk of drug-drug interactions. A diabetic state proves to be a fertile ground for PK-PD profile variability for several agents including antidiabetics, antibiotics, antifungals and central nervous system drugs. Such variability may necessitate careful patient monitoring. In many cases, dose adjustment or drug switching may be required to optimise therapeutic outcomes. Given the rising incidence and early onset of diabetes, it is increasingly important to understand the unique PK-PD profiles of drugs in this population. For these reasons, research into the PK-PD behaviour of drugs should be accelerated. Through heightened understanding, we envisage consensus and clear guidelines for the management of various conditions in a diabetic state would be sought.