Mean (SE) of subscales of the POMS and main effect (GLM) of Treatment Condition; T = Time of measurement (B = baseline; Peak = drug peak moment); Statistically significant treatment-placebo contrasts are flagged with an ‘a’, MDMA vs pindolol + MDMA contrasts with a ‘b’.

<p>Mean (SE) of subscales of the POMS and main effect (GLM) of Treatment Condition; T =  Time of measurement (B =  baseline; Peak =  drug peak moment); Statistically significant treatment-placebo contrasts are flagged with an ‘a’, MDMA vs pindolol + MDMA contrasts with a ‘b’.</p

Schematic representation of a test day; BP = Blood Pressure, HR = Heart Rate; * T3 = first dose of 40 IU.

<p>Schematic representation of a test day; BP =  Blood Pressure, HR =  Heart Rate; * T3 =  first dose of 40 IU.</p

Oxytocin (pg/mL) and cortisol (nM or nmol/L) serum concentrations * B = Baseline; Start of test battery = 45′post-oxytocin administration, 90′post-MDMA administration, 150′post-pindolol administration; End of test battery = 120′post-oxytocin administration (first dose), 165′post-MDMA administration, 225′ post-pindolol administration; Statistically significant treatment-placebo contrasts are flagged with an ‘a’, MDMA vs pindolol + MDMA contrasts with a ‘b’.

<p>Oxytocin (pg/mL) and cortisol (nM or nmol/L) serum concentrations * B =  Baseline; Start of test battery = 45′post-oxytocin administration, 90′post-MDMA administration, 150′post-pindolol administration; End of test battery = 120′post-oxytocin administration (first dose), 165′post-MDMA administration, 225′ post-pindolol administration; Statistically significant treatment-placebo contrasts are flagged with an ‘a’, MDMA vs pindolol + MDMA contrasts with a ‘b’.</p

Mean (SE) of dependent variables of the WLT and main effects of Treatment Condition and Task Variable* (Trial); ns = not significant, na = not applicable.

<p>Mean (SE) of dependent variables of the WLT and main effects of Treatment Condition and Task Variable* (Trial); ns =  not significant, na =  not applicable.</p

Mean (SD) MDMA/MDA concentrations (µg/L) in MDMA and the combined pindolol+MDMA condition.

<p>Mean (SD) MDMA/MDA concentrations (µg/L) in MDMA and the combined pindolol+MDMA condition.</p

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

Analysis of the Adherence and Safety of Second Oral Glucose-Lowering Therapy in Routine Practice From the Mediterranean Area: A Retrospective Cohort Study

The aims of our study was compare adherence measured by the medical possession ratio (MPR), time until discontinuation and describe adverse events after adding a DPP-4i, SGLT-2i, or sulfonylureas (SU) to metformin in a primary care population with insufficient glycemic control. We used routinely-collected health data from the SIDIAP database. The included subjects were matched by propensity score. The follow-up period was up to 24 months or premature discontinuation. The primary outcomes were the percentage of subjects with good adherence, treatment discontinuation and adverse events among treatment groups. The proportion of patients with good adherence (MPR> 0.8) after the addition of DPP-4i, SGLT-2i or SU was 53.6%, 68.7%, and 43.0%, respectively. SGLT-2i users were 1.7 times more likely to achieve good adherence compared with DPP-4i users (odds ratio [OR]:1.72, 98% confidence interval [CI]:1.51, 1.96), and 2.8 times more likely compared with SU users (OR: 0.35, 98% CI: 0.07, 0.29). The discontinuation hazard ratios were 1.43 (98%CI: 1.26; 1.62) and 1.60 (98%CI: 1.42; 1.81) times higher among SGLT-2i and SU users than DPP-4i users during the follow-up period. No differences were observed for adverse events among the treatment groups. In conclusion, in our real-world setting, the combination of SGLT-2i with metformin was associated with better adherence. The mean time until discontinuation was longer in the SGLT-2i group in comparison with the DPP-4i or SU groups