LBSUN210 Efficacy And Safety Profile Of Insulin Icodec Versus Insulin Glargine U100 In Type 2 Diabetes Mellitus: A Meta-Analysis Of Randomized Controlled Trials

In the context of diabetes, clinical inertia is defined as the failure to initiate insulin therapy or its intensification when treatment goals have not been met. Patient-related factors that contribute to this phenomenon include inability to follow complex regimens, cost of treatment and drug side effects. Icodec is a novel, investigational, ultra-long acting, once-weekly insulin analog with a potential for better treatment adherence. However, early evidence from phase 2 trials on icodec in type 2 diabetes mellitus (T2D) is conflicting. To study the efficacy and safety of insulin icodec, we conducted a meta-analysis of published randomized controlled trials (RCTs) on weekly icodec vs. daily glargine U100 in patients with uncontrolled T2D (HbA1c > 7%). A systematic search in major online databases was done to identify and review relevant RCTs. Two authors independently performed the study selection and extracted study data. Data on glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), time-in-range of 70-180 mg/dL (TIR), adverse events and hypoglycemia events were noted. Significance level of 95% was used to provide pooled estimates. Random effects model was used for analysis with significant heterogeneity (I2>50%). Three trials with 606 patients were included. Pooled analysis of available data showed that icodec resulted in a significantly greater mean reduction of HbA1c (mean difference (MD)=0.18%[0.13,0.22], p<0. 00001, I2=84% in 2 studies), mean reduction of FPG (MD=3.87mg/dl [3.18, 4.57],p<0. 00001, I2=0%), longer TIR (MD=4.39% [3.94, 4.85], p<0. 00001, I2=0%), but had significantly greater propensity to lead to level 1 hypoglycemia (Odds Ratio (OR)=1.59 [1.11,2.28], p=0. 01, I2=29%) when compared to glargine U100. Funnel plot analysis on the propensity for icodec to lead to any hypoglycemia event decreased the I2 statistic from 78% to 0% and showed significantly greater hypoglycemia events with icodec (OR=2.59 [1.67,4. 01], p<0. 001). There was no significant difference in the number of patients with end-of-trial HbA1c <7%, and any adverse event, or hypoglycemia level 2 or 3. Of note, only one hypoglycemia level 3 event was noted (patient on icodec). Once-weekly icodec had significantly better glycemic control compared to daily glargine U100, but had significantly greater hypoglycemia events. Data from ongoing trials on this novel drug can be added to the analysis as they become available. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.