SUN-LB115 Is the Stepping-Down Approach a Better Option Than Multiple Daily Injections in Patients With Chronic Poorly-Controlled Diabetes on Advanced Insulin Therapy?

In the traditional step-up approach, patients with poorly-controlled T2DM are eventually advanced to multiple daily insulin injections (MDI). However, some on advanced insulin therapy (AIT) continue to have poor control due to poor compliance with MDI and fear of insulin-induced weight gain. The recent guidelines recommend the use of anti-hyperglycemic agents with weight loss benefits, such as SGLT2i or GLP1 RA, with basal insulin before the patients are advanced to MDI. Objective: To determine if de-escalating from AIT to the combined use of metformin, SGLT2i, GLP1 RA and basal insulin by using the stepping-down approach is a better option than MDI in obese patients with poorly- controlled T2DM on AIT. Research Design: This pilot, prospective, randomized, open-label, controlled, parallel-group trial enrolled 22 obese patients with T2DM on AIT, who had BMI ≥30 kg/m2, A1c >8% and eGFR >45. Patients were randomized to either intervention (Step-Down) or control (MDI) group. In the control group, the patient was advised to remain on MDI. In the intervention group, all prandial insulin injections were discontinued; but the patient remained on the basal insulin and metformin to which SGLT2i, Empagliflozin, and GLP1 RA, Dulaglutide, were added. They were followed up for 16 weeks. The primary outcome was A1c change and secondary outcomes were the change in fasting BG, weight, BP, HR, fasting lipids, serum Na and K, serum Cr, liver enzymes, CBC and Diabetes Medications Satisfaction (DM-SAT) scores at 16 weeks. Results: There was no difference in A1c between 2 groups (10.36% vs 9.69%;p=0.171) at baseline. However, A1c was significantly lower at 4 weeks (9.54% vs 7.31%; p=0.0088) and 16 weeks (9.7% vs 8.25%; p<0.001) in intervention group (n=10). Compared to baseline, in the control group (n=8), there was no significant change at secondary outcome variables except slightly higher SBP at 16 weeks. In intervention group, compared to baseline, there was a significant decrease in weight (-16.38 Lbs; p=0.003), BMI (-3.06; p<0.001), LDL cholesterol (-15.7 mg/d; p=0.0378), total cholesterol (-18.5 mg/dL; p=0.0386), total daily insulin dose (-57.3 units; p<0.001) and a significant improvement in DM-SAT patient satisfaction 0-100 scores - total score (+45.3; p <0.001) and subscale scores (Convenience +35.28, p =0.019; Lifestyle +35.8, p=0.0052; Medical control +51.3, p<0.001; Wellbeing +47.2,p=0.0091) at 16 weeks. Conclusions: De-escalating from AIT to the combined use of metformin, SGLT2i, GLP1 RA and basal insulin in obese patients with poorly-controlled T2DM by using the stepping-down approach results in the significant improvement in glycemic control, weight loss, and significantly higher patient satisfaction. This noble stepping-down approach may be a better option than continuing MDI in such patients. This pilot study result needs to be confirmed with a larger trial. ClinicalTrials ID: NCT02846233