Efficacy and Safety of Once-weekly IcoSema in Adults with Type 2 Diabetes: A Systematic Review and Meta-Analysis

To evaluate the effectiveness and safety of once-weekly IcoSema compared to its components, icodec and semaglutide, as well as daily basal-bolus insulin therapy in type 2 diabetes. Randomized controlled trials (RCTs) of IcoSema in type 2 diabetes were identified through a thorough search of electronic databases. Coprimary outcomes were changes in glycated hemoglobin (HbA1c) and body weight. Meta-analyses were conducted using the RevMan web program with a random-effects model, showing results as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CIs). Three low-bias RCTs with 2653 subjects were included. IcoSema outperformed the control arm in lowering HbA1c (MD -0.39%, 95% CI [-0.71, -0.07], P = 0.02, I2 = 95%). Both groups achieved comparable changes in body weight (MD -2.59 kg, 95% CI [-9.54, 4.36], P = 0.47, I2 = 100%). More subjects achieved HbA1c <7.0% (RR 1.54) and HbA1c <7.0% without clinically significant or severe hypoglycemia (RR 1.85) with IcoSema than with control. Both groups showed similar changes in fasting plasma glucose, waist circumference, and blood pressure. continuous glucose monitoring metrics were also comparable. IcoSema increased the risk of total adverse events (AEs), but rates of severe, serious, and cardiovascular AEs were similar. IcoSema lowered the risk of clinically significant hypoglycemia, but not severe hypoglycemia. It was well-tolerated without increasing gastrointestinal AEs, retinopathy, or infections; however, it increased headache risk and decreased appetite. IcoSema offers better glycemic control and less hypoglycemia risk than controls, with comparable safety for serious AEs. More RCTs involving diverse populations are needed to improve clinical decision-making.