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

Aim: 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. Methods: 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. Results: 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. Conclusion: 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