What Next After Metformin in Type 2 Diabetes? Selecting the Right Drug for the Right Patient

Abstract

Introduction: Metformin is the recommended initial treatment in type 2 diabetes mellitus (T2DM), but when this does not give adequate glucose control the choice of which second-line drug to use is uncertain as none have been found to have a better overall glycaemic response. In this real-world study dipeptidyl peptidase 4 inhibitors (DPP4i), sulphonylureas (SU), thiazolidinediones (TZD) and sodium glucose co-transporter 2 inhibitors (SGLT2i) were compared for their effectiveness in lowering glycated haemoglobin (HbA1c) levels for a particular individual based on their clinical characteristics. Methods: A retrospective analysis was undertaken of electronic health records of people with T2DM prescribed metformin alongside a DPP4i, SU, TZD or SGLT2i at second-line. Regression modelling was used to model the changes in HbA1c from baseline at month 6 and month 12 for the individual therapies, adjusting for demographic and clinical characteristics. Results: There were 7170 people included in the study. Treatment at second-line with SUs, DPP4i, TZDs and SGLT2i resulted in similar percentages of people achieving the recommended HbA1c target of < 7.5% (58 mmol/mol) at both 6 and 12 months. For those receiving SGLT2i and SUs, the greatest improvement in HbA1c was observed in relatively younger and older people, respectively. Trends were detected between other baseline characteristics and HbA1c improvement by drug class, but they were not statistically significant. Non-adherence rates were low for all drug classes. People with a higher medication possession ratio (≥ 80%) also had greater improvements in HbA1c at 12 months. Conclusion: This study identified patients’ phenotypic characteristics that may have the potential to influence individual treatment response. Accounting for these characteristics in clinical treatment decisions may facilitate individualised prescribing by being able to select the right drug for the right patient.