Introduction
Once-weekly insulins
Pharmacokinetic considerations
Data from Phase II randomised clinical trials
Characteristic | Icodec | BIF | ||||
---|---|---|---|---|---|---|
Rosenstock 2020 [23] | Bajaj 2021 [25] | Lingvay 2021 [24] | Frias 2023 [26] | Bue-Valleskey 2023 [27] | Kazda 2023 [28] | |
Features | ||||||
Design | Double-blind | Open-label | Open-label | Open-label | Open-label | Open-label |
Duration | 26 weeks | 16 weeks | 16 weeks | 32 weeks | 26 weeks | 26 weeks |
Participant | Insulin-naive participants with T2D | Insulin-treated participants with T2D | Insulin-naive participants with T2D | Insulin-treated participants with T2D | Insulin-naive participants with T2D | T1D participants on multiple daily injections |
Comparator | Glargine U100 | Glargine U100 | Glargine U100 | Degludec | Degludec | Degludec |
Glucose targets (mmol/mol) | 3.9–6.0 (both arms) | 4.44–7.22 (both arms) | 4.44–7.22 (icodec A and B and glargine U100); 3.89–5.99 (icodec C) | ≤7.8 (BIF-A1); ≤6.7 (BIF-A2); ≤5.6 (degludec) | 4.4–5.6 (both groups) | 4.4–5.6 (both groups); 5.6–7.8 for BIF in first 2 weeks |
No. of participants | 247 (125 icodec, 122 glargine U100) | 154 (54 icodec LD, 50 icodec NLD, 50 glargine U100) | 205 (icodec A 51, B 51, C 52, glargine U100 51) | 399 (135 BIF-A1, 132 BIF-A2, 132 degludec) | 278 (143 BIF, 135 degludec) | 265 (139 BIF, 126 degludec) |
Baseline HbA1c, mean±SD | ||||||
mmol/mol | 64±7.7 | 63±7.7 | 65±7.7 | 65±9.8 | 64±8.7 | 58±9.8 |
% | 8.0±0.7 | 7.9±0.7 | 8.1±0.7 | 8.1±0.9 | 8.1±0.8 | 8.1±0.9 |
Baseline treatment | Metformin ± DPP4i | Basal insulin + metformin ± DPP4i/SGLT2i | Metformin ± DPP4i/SGLT2i | Basal insulin ± up to three non-insulin drugs | Metformin ± DPP4i/SGLT2i | Multiple daily insulin injections |
Glucose monitoring | Flash glucose monitoring (weeks 25−26) | Dexcom G6 | Dexcom G6 | Dexcom G6 | Libre Pro | Dexcom G6 |
Resultsa | ||||||
HbA1c, achieved, mmol/mol (%) | 50 (6.69) (icodec) 52 (6.87) (glargine U100) | 54 (7.1) (icodec LD) 57 (7.4) (icodec NLD) 57 (7.4) (glargine U100) | 54 (7.1) (icodec A) 52 (6.9) (icodec B) 50 (6.7) (icodec C) 54 (7.1) (glargine U100) | 60 (7.6) (BIF-A1) 57 (7.4) (BIF-A2) 57 (7.4) (degludec) | 51 (6.8) (BIF) 50 (6.7) (degludec) | 58 (7.5) (BIF) 57 (7.3) (degludec) |
TIR (3.9–10.0 mmol/l) (%) | NA | 72.9 (icodec LD) 66.0 (icodec NLD) 65.0 (glargine U100) | 76.6 (icodec A) 83.0 (icodec B) 80.9 (icodec C) 75.9 (glargine U100) | 60.5 (BIF-A1) 62.2 (BIF-A2) 63 (degludec) | 76.0 (BIF) 77.4 (degludec) | 56.1 (BIF) 58.9 (degludec) |
Time in tight range (3.9−7.8 mmol/l) (%) | 66.11 (icodec) 60.71 (glargine U100) | NA | NA | NA | NA | NA |
Time below range (<3.9 mmol/l) (%) | NA | 1.6 (icodec LD) 0.6 (icodec NLD) 0.5 (glargine U100) | 1.0 (icodec A) 1.4 (icodec B) 1.9 (icodec C) 0.7 (glargine U100) | 0.5 (BIF-A1) 0.7 (BIF-A2) 0.8 (degludec) | 0.80 (BIF) 1.55 (degludec) | 2.49 (BIF) 2.77 (degludec) |
Body weight change (kg) | 1.49 (icodec) 1.56 (glargine U100) | 0.6 (icodec LD) 1.3 (icodec NLD) 0.1 (glargine U100) | 0.9 (icodec A) 1.1 (icodec B) 1.3 (icodec C) 0.6 (glargine U100) | 1 (BIF-A1) 1 (BIF-A2) 2 (degludec) | 2.9 (BIF) 2.5 (degludec) | 0.1 (BIF) 0.6 (degludec) |
Level 1 hypoglycaemia (events/patient-year) | 5.09 (icodec) 2.11 (glargine U100) | 3.81(icodec LD) 4.29 (icodec NLD) 3.77 (glargine U100) | 0.73 (icodec A) 1.11 (icodec B) 5.38 (icodec C) 0.58 (glargine U100) | 23.0 (BIF-A1) 22.5 (BIF-A2) 30.0 (degludec) | 3.3 (BIF) 2.8 (degludec) | 207.6 (BIF) 206.7 (degludec) |
Level 2 hypoglycaemia (events/patient-year) | 0.53 (icodec) 0.46 (glargine U100) | 0.78 (icodec LD) 0.15 (icodec NLD) 0.79 (glargine U100) | 0.05 (icodec A) 0.15 (icodec B) 0.38 (icodec C) 0 (glargine U100) | 2.2 (BIF-A1) 2.4 (BIF-A2) 3.0 (degludec) | 0.22 (BIF) 0.15 (degludec) | 40.7 (BIF) 45.5 (degludec) |
Level 3 (severe) hypoglycaemia (events/patient-year) | 0.01 (icodec) 0.02 0 (glargine U100) | 0 (icodec LD) 0 (icodec NLD) 0 (glargine U100) | 0 (icodec A) 0 (icodec B) 0 (icodec C) 0 (glargine U100) | 0 (BIF-A1) 2 episodes (BIF-A2) 0 (degludec) | 0 (BIF) 0 (degludec) | 1 episode (BIF) 2 episodes (degludec) |
Ongoing Phase III programmes
Trial | Design | No. of participants | Population | Comparator | Baseline treatment | Duration (weeks) |
---|---|---|---|---|---|---|
Icodec | ||||||
ONWARDS 1 [31] | Open label | 984 | Insulin-naive participants with T2D | Glargine U100 | Any non-insulin drugs | 78 |
ONWARDS 2 [32] | Open label | 526 | Insulin-treated participants with T2D | Degludec | Basal insulins ± non-insulin glucose-lowering agents | 26 |
ONWARDS 3 [29] | Double-blind | 588 | Insulin-naive participants with T2D | Degludec | Any non-insulin drugs | 26 |
ONWARDS 4 [33] | Open label | 582 | Insulin-treated participants with T2D | Glargine U100 | Multiple daily insulin injections ± non-insulin drugs | 26 |
ONWARDS 5 [30] | Open label | 1085 | Insulin-naive participants with T2D | Glargine U100/300 and degludec | Any non-insulin drugs | 52 |
ONWARDS 6 [34] | Open label | 583 | Participants with T1D | Degludec | Multiple daily insulin injections | 52 |
BIF | ||||||
QWINT-1 [38] | Open label | 670 | Insulin-naive participants with T2D | Glargine U100 | At least one glucose-lowering medication | 52 |
QWINT-2 [41] | Open label | 912 | Insulin-naive participants with T2D | Degludec | At least one glucose-lowering medication | 52 |
QWINT-3 [42] | Open label | 986 | Insulin-treated participants with T2D | Degludec | Basal insulins ± up to three non-insulin drugs (except SUs) | 78 |
QWINT-4 [40] | Open label | 670 | Insulin-treated participants with T2D | Glargine U100 | Multiple daily insulin injections | 26 |
QWINT-5 [39] | Open label | 670 | Participants with T1D | Degludec | Multiple daily insulin injections | 52 |