Analysis of the effectiveness of second oral glucose-lowering therapy in routine clinical practice from the mediterranean area: A retrospective cohort study

•Addition of a SGLT-2i to metformin was associated with greater weight reduction.•Addition of a SGLT-2i to metformin is associated with HbA1c and weight reduction.•HbA1c reduction was similar after addition of SGLT-2i, DPP4i or SU to metformin.•The treatment intensification in our primary care settings is far from optimal. To compare the changes in HbA1c, the effect on body weight or both combined after the addition of a DPP-4i, SGLT-2i, or sulfonylureas (SU) to metformin in real-world condition. We used a primary care SIDIAP database. The included subjects were matched by propensity score according to baseline age, sex, HbA1c, weight, inclusion date, diabetes duration, and kidney function. Mean absolute HbA1c reduction was: 1.28% for DPP4i, 1.29% for SGLT2i and 1.26% for SU. Mean weight reduction was: 1.21 kg for DPP4i, 3.47 kg for SGLT2i and 0.04 kg for SU. The proportion of patients who achieved combined target HbA1c (≥0.5%) and weight (≥3%) reductions after the addition of DPP-4i, SGLT-2i or SU, was: 24.2%, 41.3%, and 15.2%, respectively. Small differences in systolic blood pressure reduction (1.07, 3.10 and 0.96 mmHg, respectively) were observed in favour of SGLT-2i. Concerning the lipids, we observed small differences, with an HDL-cholesterol increase with SGLT-2i. Our real-world study showed that the addition of SGLT-2i to metformin was associated with greater reductions in weight and the combination target of weight-HbA1c compared to SU and DPP4 inhibitors. However, similar hypoglycaemic effectiveness was observed among the three-drug classes.