Impact on Glycaemic Variability in Newly Onset T2DM Patients Initiating Dapagliflozin Plus Metformin vs. Metformin Alone, a Randomized Open Label Clinical Study-The MAGNNIFY Trial

Background: The aim of this study is to compare the effect of dapagliflozin (DAPA) in addition to metformin (MET) at maximum tolerated dose in glycaemic variability (GV) on drug naïve T2DM patients. ClinicalTrials.gov Identifier: NCT04090580 Methods: Newly diagnosed T2DM patients with HbA1c ≥ 7.5% - ≤ 12%, BMI > 25 - <45 kg/m2, were randomized 1:1 to receive DAPA 10 mg + MET or MET alone for 12 weeks. Both groups were monitored using a CGM system for 7 days at baseline and week 12. Primary outcome was defined as the mean difference of MAGE (Mean Amplitude of Glycaemic Excursions). Additional secondary endpoints included mean difference of serum insulin, HbA1c, weight, and time in range. Results: 80 patients completed follow-up at week 12 (DAPA+MET, n=41; MET, n=39). Baseline characteristics included mean age 52.2±10.4 years, weight 80.6±16.5 kg, SBP 133.3±19.3 mmHg, HbA1c 9.3±1.5 %, eGFR 100.5±15.4 ml/min/1.73m2, MAGE 4.2±1.4 mmol/L. Patients treated with DAPA+MET had lower GV at week 12 measured by MAGE (-0.79 [-0.86 DAPA+MET vs -0.06 MET; p=0.018]) and higher time in range (+22.9% [35.8 DAPA+MET vs 12.9 MET; p=0.002]). DAPA group had lower insulin plasma levels (-4.5 µU/mL [-2.8 DAPA+MET vs +1.6 MET; p=0.029]) and body weight (-3.2 kg [-3.22 DAPA+MET vs -0.6 MET; p<0.001]); nominal reductions were observed in HbA1c (-1.82 DAPA+MET vs -1.61 MET; p=0.919) and SBP (-4.96 mmHg [-4.35 DAPA+MET vs +0.60 MET; p=0.277]. Conclusions: Patients with new onset T2DM treated with DAPA + MET during a 12-week period had improvements in glycaemic variability measured by MAGE (-19.63%) and achieved longer periods within target range for glycaemic control in comparison with patients treated only with MET. Plasmatic insulin levels, and weight reduction were also significantly reduced with DAPA; nominal reductions in HbA1c and SBP were observed. All these findings support the early dapagliflozin use in patients with newly onset T2DM. Disclosure A.P.Guerrero-castillo: None. S.C.Juarez-comboni: Employee; AstraZeneca. F.J.Gómez-perez: None. M.A.Gomez-samano: Research Support; AstraZeneca. A.Benitez-renteria: Employee; AstraZeneca. D.Cuevas-ramos: None. M.López-carrasco: None. A.Silva: Stock/Shareholder; AstraZeneca. G.X.Brito: None. L.Palacios-baez: None. I.Manjarrez-martínez: None. S.I.Rodriguez-carranza: None. Funding AstraZeneca Mexico