Introduction
Versatility and Flexibility
Evidence from Randomized Controlled Trials
Real-World Evidence
Study | Study details | Study endpoints summary |
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IDegAsp OD with largest meal of the day (BOOST: JAPAN) Comparator: IGlar OD [10] | 26-week, open-label, randomized, treat-to-target trial Patients: T2DM, Insulin-naïve previously treated with OADs (n = 296) | Superior long-term glycemic control with IDegAsp vs. IGlar (ETD IDegAsp–IGlar, − 0.28% (95% CI − 0.46; − 0.10), p < 0.001) IDegAsp was superior to IGlar with respect to lowering postprandial glucose at the main evening meal (p < 0.001) Lower rates of overall confirmed (27%) and nocturnal confirmed hypoglycemia (25%) with IDegAsp vs. IGlar |
(TWICE DAILY IDegAsp vs. BB) Comparator: IDeg OD + IAsp (2–4 injections/day) [11] | 26-week, randomized, open-label, crossover trial. Patients: T2DM, currently treated with basal insulin (IDet, IGlar, NPH) ± OADs (n = 274) | Reduction in HbA1c was comparable between treatment groups but non-inferiority was not confirmed [ETD, 0.10% points (95% CI − 0.04; 0.41)] Change in body weight and insulin dose were both lower with IDegAsp BID compared with IDeg OD + IAsp Total insulin was significantly lower for IDegAsp BID vs. IDeg + IAsp [1.11 vs. 1.34 U/kg; estimated ratio, 0.88 (95% CI 0.78; 1.00), p < 0.05] Rates of confirmed (19%) and nocturnal confirmed hypoglycemia (20%) were numerically lower with IDegAsp BID compared with IDeg OD + IAsp |
IDegAsp OD with main meal and IAsp with other meals (BOOST:T1) Comparator: IDet OD or BID + IAsp as mealtime insulin [14] | 26-week, multinational, open-label, parallel-group, treat-to-target trial Patients: T1DM, treated with basal bolus, premixed insulin, or self-mix regimens (n = 548) | Non-inferiority for IDegAsp vs. IDet in HbA1c reduction [0.75% vs. 0.70%; ETD, − 0.05% (95% CI − 0.18; 0.08)] 37% lower rates of nocturnal confirmed hypoglycemia with IDegAsp vs. IDet (3.71 vs. 5.72 episodes/patient-year, p < 0.05) Total insulin dose was 13% lower in the IDegAsp group (p < 0.0001) |
IDegAsp BID (BOOST: INTENSIFY PREMIX I) Comparator: BIAsp 30 BID [13] | 26-week, phase 3a, open-label, randomized, treat-to-target trial Patients: T2DM, previously treated with premixed insulin (OD or BID) ± OADs ≥ 3 months (n = 447) | Non-inferiority for IDegAsp vs. BIAsp 30 in HbA1c reduction from baseline [ETD, − 0.03% (95% CI − 0.18; 0.13)] Superior FPG reduction with IDegAsp vs. BIAsp 30 [ETD, − 20.54 mg/dL (95% CI − 27.57; − 13.70), p < 0.001] Estimated mean of the 9-point SMPG profile was significantly different between treatments [ETD IDegAsp–BIAsp 30, − 7.21 mg/dL (95% CI − 13.52; − 0.90), p < 0.05] Total insulin dose at the end of trial was 11% lower for IDegAsp vs. BIAsp 30 [rate ratio IDegAsp/BIAsp 30, 0.89 (95% CI 0.83; 0.96), p = 0.0021] 32% lower rates of confirmed hypoglycemia (p = 0.0049) and 73% lower rates of nocturnal confirmed hypoglycemia with IDegAsp vs. BIAsp 30 (p < 0.0001) |
IDegAsp BID (BOOST: INTENSIFY ALL) Comparator: BIAsp 30 BID [15] | 26-week, phase 3, open-label, randomized, treat-to-target trial. Patients: T2DM, Asian/previously treated with basal, premixed or self-mixed insulin ± metformin ≥ 3 months (n = 424) | Non-inferiority for IDegAsp vs. BIAsp 30 in HbA1c reduction (ETD, 0.05% (95% CI − 0.10; 0.20), p = 0.20) Superior FPG reduction with IDegAsp vs. BIAsp 30 (ETD IDegAsp–BIAsp 30, − 19.10 mg/dL, p < 0.001) Total insulin dose at the end of trial was 21% lower for IDegAsp vs. BIAsp 30 [rate ratio IDegAsp/BIAsp 30, 0.79 (95% CI 0.73; 0.85), p < 0.0001] Lower rates of overall confirmed and severe hypoglycemia and numerically lower rate for nocturnal confirmed hypoglycemia (33%) were observed for IDegAsp vs. BIAsp 30 |
IDegAsp BID Comparator: BIAsp 30 BID [12] | 26-week, multinational, open-label, parallel-group, treat-to-target trial Patients: T2DM, insulin-naïve uncontrolled on their current therapy of metformin (≥ 1000 mg daily) ± one additional OHA for at least 12 weeks before randomization (n = 394) | Insulin degludec/insulin aspart was non-inferiority to BIAsp 30 (ETD, 0.02%; 95% CI 0.12, 0.17) Insulin degludec/insulin aspart was superior in lowering fasting plasma glucose (ETD 1.00 mmol/l; 95% CI 1.4, 0.6; p < 0.001) Superiority of IDegAsp was demonstrated, with a 54% reduction in overall confirmed hypoglycemia at similar overall insulin dose compared to biphasic insulin aspart 30 Superiority of IDegAsp was also demonstrated for nocturnal hypoglycemia, with a 75% reduction (estimated rate ratio, 0.25; 95% CI 0.16, 0.38; p < 0.001) |
IDegAsp use in Indian population for initiation and intensification [6] | 52 weeks, retrospective study Patients: all subjects who had received IDegAsp for 52 weeks at two endocrine centers (n = 48) | HbA1c was 7.51 ± 0.46% at 26 weeks and 7.48 ± 0.40% at 52 weeks FPG was 108.58 ± 22.26 mg % at 26 weeks and 102.17 ± 12.79 mg % at 52 weeks 39 (81.25%) achieved a target of HbA1c < 7.0% at both 26 and 52 weeks No episode of hypoglycemia was reported in 4 weeks preceding the analysis Dose of IDegAsp fell from 43.17 ± 21.18 to 37.75 ± 17.13 U/day at 24 weeks and 41.41 ± 15.33 U/day at 52 weeks |
Eminent Experience
Concordance
Consensus: Initiation with Insulin Degludec/Aspart (IDegAsp)
Indications
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The consensus group recommends the use of IDegAsp for initiation of insulin in
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Drug-naïve persons with
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Symptoms of hyperglycemia.
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High carbohydrate diet.
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High HbA1c.
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High postprandial excursion.
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Insulin-naïve persons with inadequate response to metformin, dual or triple oral therapy.
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Long-acting sulfonylureas and IDegAsp, if used together, should be administered at antipodal meals.
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Administration and Titration
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The consensus group recommends the use of IDegAsp for insulin initiation in once daily or twice daily subcutaneous dosage, depending upon
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Meal pattern and quantity
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Gluco-phenotype (glucose profile)
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The starting dose of IDegAsp is usually 10 U or 0.1–0.2 U/day, but will vary according to
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Severity of hyperglycemia
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Risk of hypoglycemia
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Meal pattern and quantity
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Weight of the patient
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IDegAsp use should be monitored by regular self-monitoring of blood glucose
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Twice weekly when glycemic control is unstable, hypoglycemia is anticipated, or urgent resolution of hyperglycemia is needed.
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Once weekly when glycemic control is stable and no fluctuations are anticipated.
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More frequently if glycemic control is brittle.
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Once prebreakfast and predinner control is achieved, postprandial glucose monitoring can be done to titrate doses further.
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Advantages
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Glycemic control better or equivalent to
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Basal regimen, if used once daily
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Basal plus regimen, if used once daily
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Basal bolus regimen, if used twice daily
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Premix therapy
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Flexibility in timing of administration
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Lower risk of
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Hypoglycemia
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Nocturnal hypoglycemia
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Special Situations
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In pregnancy and lactation
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As the only insulin in diabetic ketoacidosis
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Intravenously
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Shift workers/those with erratic meal patterns
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Ramadan fasting
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Renal impairment
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Hepatic impairment
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Elderly population
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Type 1 diabetes
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Persons in whom early correction of hyperglycemia is required