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

Background: Previously 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.

Methods: Databases 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.

Results: Data 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; I = 92 %], better HbA1c lowering at 26-weeks [MD-0.19 %(95%CI: 0.35-0.013); P = 0.02; I = 94 %] and 52-weeks [MD -0.28 %(95%CI: 0.45-0.12); P = 0.0008; I = 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; I = 80 %], and higher at 52-weeks [OR1.55(95%CI:1.30-1.85); P < 0.00001; I = 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; I = 28 %] and 52-weeks [OR1.48(95%CI:1.24-1.77); P < 0.001; I = 0 %]. At 26-weeks, injection-site reactions was higher with icodec [OR1.95(95%CI:1.06-3.56); P = 0.03; I = 0 %]. At 26-weeks level-1 hypoglycemia [OR1.40(95%CI:1.02-1.94); P = 0.04; I = 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; I = 98 %].

Conclusion: Icodec insulin is well tolerated with glycaemic efficacy similar to all other available basal insulins.