Partial non-adherence to antidiabetic therapy undermines diabetes management and correlates with treatment...

To evaluate medication adherence in patients with type 2 diabetes (T2D) using plasma drug measurements and assess the clinical impact of partial non-adherence on glycemic control and complications.

This cross-sectional study included 641 T2D outpatients attending routine follow-up visits. After overnight fasting, blood samples were collected and analysed by LC-MS to quantify plasma concentrations of 13 oral antidiabetic drugs. Adherence was defined as the detection of a prescribed drug above the limit of quantification. Self-reported lifestyle factors, dosing regimens, and clinical outcomes were assessed in relation to drug presence.

Metformin adherence was very high, with the drug undetected in only 1.9% of patients. In contrast, adherence rates were lower for sulfonylureas (94%), DPP-4 inhibitors (90%), pioglitazone (82%), and SGLT2 inhibitors (73%). Non-adherence was predominantly partial: only one of the analysed antidiabetics taken by patients was not detected in 93% of non-adherent patients. Adherence declined with increasing numbers of prescribed agents and daily doses, suggesting treatment complexity as a key factor. No other tested lifestyle or drug management parameters were significantly associated with adherence. Glycemic control was worse in non-adherent patients: 63% did not reach target glucose and HbA1_c levels, compared to 37% of fully adherent patients. Non-adherence was also associated with a higher prevalence of diabetic kidney disease.

Partial non-adherence is common in T2D and strongly associated with treatment complexity and poor glycemic outcomes. These findings emphasize the need for individualized strategies to support adherence and improve long-term diabetes care. Our study further indicates that plasma analysis using LC-MS methods may serve as a robust tool for adherence assessment.