People with type 2 diabetes (T2D) and healthcare professionals can be reluctant to start insulin therapy. |
IDegLira is a medicine that combines insulin with a glucagon-like peptide-1 receptor agonist, that can help people with T2D improve their blood sugar and reduce their risk of weight gain and hypoglycemia. |
IDegLira allows for simple dose adjustment with a once daily injection, which combined with clinical benefits, may make it a more attractive option for those reluctant to start insulin. |
1 Introduction
2 Unmet Clinical Need
3 Pharmacokinetic and Pharmacodynamic Properties of IDegLira and Its Constituents
3.1 Pharmacokinetic and Pharmacodynamic Properties of Degludec
3.2 Pharmacokinetic and Pharmacodynamic Properties of Liraglutide
3.3 Pharmacokinetic and Pharmacodynamic Properties of IDegLira
4 Degludec and Liraglutide Clinical Trials
4.1 Degludec Clinical Trials
4.2 Liraglutide Clinical Trials
5 Efficacy of Basal Insulin and GLP-1RA in Free Combination
6 IDegLira Clinical Trials
Previous treatment regimen | DUAL trial | Study design | Previous regimena | HbA1c range for inclusion | Comparators | Starting dose | Maximum dose | Titration schedule |
---|---|---|---|---|---|---|---|---|
OAD(s) | DUAL I | 26-Week, randomized, open-label (N = 1663) | Metformin ± pioglitazone | 7.0–10.0% (53–86 mmol/mol) | Degludec and liraglutide | 10 units/dose steps IDegLira; 10 units degludec; 0.6 liraglutide | IDegLira titrated to a maximum 50 units/dose steps; degludec no maximum dose; liraglutide 1.8 mg | IDegLira and degludec were titrated twice per week based on a pre-breakfast target SMBG of 4–5 mmol/L |
DUAL IV | 26-Week, randomized, double-blind (N = 435) | SU ± metformin | 7.0–9.0% (53–75 mmol/mol) | Placebo | 10 units/dose steps IDegLira; matching placebo | IDegLira and placebo titrated to a maximum 50 units/dose steps | IDegLira and degludec were titrated twice per week based on a pre-breakfast target SMBG of 4–6 mmol/L | |
DUAL VI | 32-Week, randomized, open-label (N = 420) | Metformin ± pioglitazone | 7.0–10.0% (53–86 mmol/mol) | Once-weekly IDegLira titration | 10 units/dose steps IDegLira | IDegLira titrated to a maximum 50 units/dose steps | IDegLira was titrated either once weekly or twice weekly based on a pre-breakfast target SMBG of 4–5 mmol/L | |
DUAL VIII | 104-Week randomized, open-label (N = 1012) | Metformin ± SU ± glinides ± pioglitazone ± DPP-4i | 7.0–11.0% (53–97 mmol/mol) | IGlar U100 | 10 units/dose steps IDegLira; 10 units of IGlar U100 | IDegLira titrated to a maximum 50 units/dose steps; IGlar U100 no maximum dose | IDegLira was titrated twice weekly based on a pre-breakfast target SMBG of 4–5 mmol/L | |
DUAL IX | 26-Week, randomized, open-label (N = 420) | SGLT2i ± metformin ± DPP4i ± pioglitazone | 7.0–11.0% (53–97 mmol/mol) | IGlar U100 | 10 units/dose steps IDegLira; 10 units of IGlar U100 | IDegLira titrated to a maximum 50 units/dose steps; no maximum dose for IGlar, SGLT2i and OAD | IDegLira and IGlar U100 were titrated twice per week based on a pre-breakfast target SMBG of 4–5 mmol/L | |
GLP-1RA | DUAL III | 26-Week, randomized, open-label (N = 438) | GLP-1RA + metformin ± SU ± glinides ± pioglitazone | 7.0–9.0% (53–75 mmol/mol) | Pre-trial liraglutide or exenatide | 16 units/dose steps IDegLira; pre-trial dose (maximum dose) of GLP-1RA | IDegLira titrated to a maximum 50 units/dose steps | IDegLira was titrated twice per week based on a pre-breakfast target SMBG of 4–5 mmol/L |
Basal insulin | DUAL II | 26-Week, randomized, double-blind (N = 413) | Basal insulin (20–40 U) + metformin ± SU or glinides | 7.5–10.0% (59–86 mmol/mol) | Degludec | 16 units/dose steps IDegLira; 16 units degludec | IDegLira titrated to a maximum 50 units/dose steps; degludec had a maximum dose of 50 units | IDegLira and degludec were titrated twice weekly based on a pre-breakfast target SMBG of 4–5 mmol/L |
DUAL V | 26-Week, randomized, open-label (N = 557) | Metformin + IGlar U100 (20–50 U) | 7.0–10.0% (53–86 mmol/mol) | IGlar U100 | 16 units/dose steps IDegLira; pre-trial dose of IGlar | IDegLira titrated to a maximum 50 units/dose steps; IGlar U100 no maximum dose | IDegLira and IGlar U100 were titrated twice weekly based on a pre-breakfast target SMBG of 4–5 mmol/L | |
DUAL VII | 26-week, randomized, open-label (N = 506) | Metformin + IGlar U100 (20–50 U) | 7.0–10.0% (53–86 mmol/mol) | IGlar U100 + IAsp (≤ 4 times) | 16 units/dose steps IDegLira; IGlar U100 at a dose equivalent to the pre-trial dose; IAsp at 4 units at each main meal | IDegLira titrated to a maximum 50 units/dose steps; no maximum dose for IGlar U100 or IAsp | IDegLira and IGlar U100 were titrated twice weekly, aiming for a mean fasting SMBG target range of 4.0–5.0 mmol/L; IAsp was titrated twice weekly, aiming for a mean pre-prandial and bedtime SMBG target range of 4.0–6.0 mmol/L |
• IDegLira provides reductions in HbA1c to all patient groups with T2D regardless of their prior treatment (DUAL I–VII and IX) |
• Despite this level of glucose-lowering efficacy, people randomized to IDegLira experienced fewer hypoglycemic episodes compared with those treated with basal or basal–bolus insulin therapy (DUAL I, II, V, VII, and IX) |
• On average, people transferring from basal insulin to IDegLira experienced beneficial body weight reduction or stabilization, compared with people treated with continued basal or basal–bolus therapy (DUAL II, V and VII) |
• IDegLira is associated with a lower incidence of GI adverse events compared with liraglutide or exenatide (DUAL I extension and DUAL III) |
• IDegLira is an efficacious treatment option for people who do not achieve sufficient glycemic control with regimens containing sulfonylureas with or without metformin or basal insulin with or without metformin (DUAL IV, V and VII) |
• Insulin-naïve people with T2D experienced greater durability of glycemic control when treated with IDegLira compared with IGlar U100 (DUAL VIII) |
• IDegLira has a simple intensification regimen for people with T2D not reaching their glycemic targets on injectable therapy, as it enables intensification without additional daily injections (DUAL II, III, V, and VII) |
• People switching to using IDegLira instead of adding bolus insulin to a basal insulin-based regimen can avoid the inconvenience of multiple daily insulin injections and reduce their total daily insulin dose in addition to benefiting from reductions in body weight and HbA1c (DUAL VII) |
6.1 Insulin-Naïve People Receiving Antidiabetes Drugs (OADs)
6.1.1 DUAL I: IDegLira Compared with Both Degludec and Liraglutide
Previous treatment regimen | DUAL trial | Treatment group | Nausea (events per 100 PYE) | Diarrhea (events per 100 PYE) | Vomiting (events per 100 PYE) |
---|---|---|---|---|---|
OAD(s) | DUAL I | IDegLira | 20.9 | 23.5 | 10.1 |
Degludec | 8.8 | 10.3 | 3.1 | ||
Liraglutide | 54.3 | 39.8 | 23.6 | ||
DUAL IV | IDegLira | 11.3 | 10.5 | 5.3 | |
Placebo | 8.0 | 12.9 | 6.4 | ||
DUAL VI | IDegLira 1WT | 13.1 | 4.9 | 3.3 | |
IDegLira 2WT | 15.7 | 5.5 | 3.1 | ||
DUAL VIII | IDegLira | 4.9 | 6.4 | 2.9 | |
IGlar U100 | 1.4 | 2.2 | 1.7 | ||
DUAL IX | IDegLira | 21.3 | 12.6 | 4.8 | |
IGlar U100 | 1.9 | 7.6 | 3.8 | ||
GLP-1RA | DUAL III | IDegLira | 7.8 | 12.8 | 2.8 |
Pre-trial liraglutide or exenatide | 10.6 | 13.7 | 9.1 | ||
Basal insulin | DUAL II | IDegLira | 21.8 | 22.8 | 9.8 |
Degludec | 7.8 | 8.9 | NR | ||
DUAL V | IDegLira | 26.2 | 17.7 | 17.0 | |
IGlar U100 | 2.2 | 7.4 | 3.7 | ||
DUAL VII | IDegLira | 30.7 | 19.9 | 10.0 | |
IGlar U100 + IAsp (≤ 4 times) | 3.4 | 14.2 | 5.9 |
6.1.2 DUAL IV: IDegLira Compared with Placebo
6.1.3 DUAL VI: IDegLira Once-Weekly Compared with Twice-Weekly Titration
6.1.4 DUAL VIII: IDegLira Compared with IGlar U100
6.1.5 DUAL IX: IDegLira Compared with IGlar U100
6.2 Insulin-Naïve People Receiving GLP-1RAs in Combination with OADs: IDegLira Compared with GLP-1RA
6.3 People Receiving Basal Insulin and OADs
6.3.1 DUAL II: IDegLira Compared with Degludec
6.3.2 DUAL V: IDegLira Compared with IGlar U100
6.3.3 DUAL VII: IDegLira Compared with Multiple Daily Insulin Injections (MDIs)
6.4 People Not Tolerating MDI Regimens
6.5 Cardiovascular (CV) Safety
7 Cost-Effectiveness Analysis of IDegLira
Treatments | Annual per participant difference in costs ($)a | Total cost savings over a participant’s lifetime | ICER (life expectancy) per life-year gained | ICER (quality-adjusted life expectancy) per QALY gained |
---|---|---|---|---|
IDegLira compared with uptitrated IGlar U100 | ||||
Davies et al. 2016 [78] | – | £1441 | £7130 | £6090 |
Hunt et al. 2017 [74] | – | $16,970 | $96,039 | $63,678 |
Hunt et al. 2017 [75] | $3546 | – | – | – |
IDegLira compared with IGlar U100 + IAsp | ||||
Davis et al. 2016 [78] | – | £1698 | IDegLira dominant | IDegLira dominant |
Dempsey et al. 2018 [77] | – | $3571 | IDegLira dominant | IDegLira dominant [$4050b] |
Dempsey et al. 2018 [77] | −$743.44 [+ $267.97a] | – | – | IDegLira dominant [$2211b] |
Drummond et al. 2018 [76] | +£303 [+ £794a] | – | – | £5924 [£15,505b] |
8 Use of IDegLira in Clinical Practice
8.1 Initiation
We recommend GLP-1RA/basal insulin FRCs such as IDegLira be considered as a first injectable therapy for people with T2D |
GLP-1RA/basal insulin FRCs should also be considered as an alternative for people with T2D not reaching their glycemic targets when treated with: • GLP-1RA monotherapy • Basal insulin—in people who might otherwise require intensification with MDIs • Twice-daily basal insulin—in people with recurrent hypoglycaemia • MDIsa |