Optimal use of once weekly icodec insulin in type-2 diabetes: An updated meta-analysis of phase-2 and phase-3 randomized controlled trials

Abstract

BackgroundPreviously published meta-analysis have analysed data from 3 small phase-2 randomized controlled trials (RCTs). Since then, 5 big phase-3 RCTs have been published on use of icodec in type-2 diabetes (T2D). This updated systematic review aimed to establish the best practices and safety of icodec in T2D. MethodsDatabases were searched for RCTs involving T2D patients receiving icodec. Primary outcome was change in HbA1c. Secondary outcomes were alterations in glycaemic parameters and adverse events. ResultsData from 8 studies (4317 patients) was analysed. Compared to other basal insulins, icodec had comparable HbA1c lowering at 16-weeks [MD-0.19 %(95%CI: 0.58–0.20); P = 0.35; I2 = 92 %], better HbA1c lowering at 26-weeks [MD-0.19 %(95%CI: 0.35–0.013); P = 0.02; I2 = 94 %] and 52-weeks [MD -0.28 %(95%CI: 0.45–0.12); P = 0.0008; I2 = 100 %]. Percentage of participants achieving HbA1c<7 % with icodec was higher at 16-weeks [OR2.37(95%CI:1.05–5.35); P = 0.04], comparable at 26-weeks [OR1.38(95%CI:0.91–2.11); P = 0.13; I2 = 80 %], and higher at 52-weeks [OR1.55(95%CI:1.30–1.85); P < 0.00001; I2 = 0 %]. Percentage of participants achieving HbA1c<7 % without level 2/3 hypoglycaemia was higher with icodec at 26-weeks [OR1.37(95%CI:1.10–1.71); P = 0.004; I2 = 28 %] and 52-weeks [OR1.48(95%CI:1.24–1.77); P < 0.001; I2 = 0 %]. At 26-weeks, injection-site reactions was higher with icodec [OR1.95(95%CI:1.06–3.56); P = 0.03; I2 = 0 %]. At 26-weeks level-1 hypoglycemia [OR1.40(95%CI:1.02–1.94); P = 0.04; I2 = 58 %], but not level-2/3 hypoglycaemia was higher with icodec. Subset analysis revealed increased occurrence of level-1 [OR 4.19 (95 % CI: 3.20–5.50); P < 0.00001] and level-2 [OR 3.97 (95 % CI: 3.04–5.18); P < 0.00001] hypoglycaemia in participants who received one-time additional 50 % icodec loading dose as compared to those who did not. At 26-weeks, weight-gain was significantly higher with icodec [MD0.61 kg(95%CI:0.38–0.84); P < 0.00001; I2 = 98 %]. ConclusionIcodec insulin is well tolerated with glycaemic efficacy similar to all other available basal insulins.