Insulin Degludec/Liraglutide: A Review in Type 2 Diabetes

AimsTo describe the real‐world use and effectiveness of IDegLira, a fixed‐ratio combination of the basal insulin degludec, and the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) liraglutide.Materials and MethodsThis European, multicentre, retrospective chart review comprised adults (n = 611) with type 2 diabetes, who started IDegLira ≥6 months before data collection. Clinical characteristics were assessed at baseline (defined as the most recent recording during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12 months (± 45 days for each time point) after commencing IDegLira, where data were available.ResultsBaseline regimens included non‐injectable medications (19%), basal insulin (19%), GLP‐1RA (10%), free combination therapy (insulin/GLP‐1RA, 24%) and multiple daily‐dose insulin injections (MDI, 28%), all ± oral antidiabetic drugs. After 6 months, significant glycated haemoglobin (HbA1c) reductions were observed in patients overall and in all subgroups (−10 mmol/mol [−0.9%] overall; P < .0001), and a significant reduction in mean body weight (−0.7 kg; P < .05) was observed in patients overall and in patients receiving MDI (−2.4 kg; P < .0001). The mean IDegLira dose was 22, 30 and 32 dose steps at initiation, and at 6 and 12 months follow‐up, respectively. In total, only 67 patients reached the maximum 50 dose steps, with most coming from the free combination therapy (n = 31) or MDI (n = 15) baseline regimen groups. Hypoglycaemia rates were reduced by 82% (rate ratio 0.18; P < .0001) in the 6‐month period after vs before IDegLira initiation. Overall, a total of 12 patients experienced 15 events in the 6 months after IDegLira initiation.ConclusionIn real‐world practice, after 6 months and at a moderate dose, IDegLira resulted in substantial reductions in HbA1c and body weight, with a reduced risk of hypoglycaemia.

Section: Discussionsupporting

confidence: 58%

Use and effectiveness of a fixed‐ratio combination of insulin degludec/liraglutide (IDegLira) in a real‐world population with type 2 diabetes: Results from a European, multicentre, retrospective chart review study

Price

Blüher

Prager

et al. 2018

“…In general, IDegLira was well‐tolerated when added to treatment with metformin ± pioglitazone. There were few different types of AEs reported for IDegLira and they were no different from what was expected from its mono‐components – insulin degludec and liraglutide …”

Section: Discussionmentioning

confidence: 99%

“…GLP‐1RAs stimulate insulin secretion while suppressing glucagon release in a glucose‐dependent manner, and are associated with weight loss and a low risk of hypoglycaemia; however, transient gastrointestinal (GI) side effects are common with initial GLP‐1RA therapy . Once‐daily GLP‐1RAs can be combined with once‐daily basal insulins as fixed‐ratio combination products such as insulin degludec with liraglutide (IDegLira) and insulin glargine with lixisenatide (iGlarLixi), thereby simplifying treatment escalation. The clinical utility of IDegLira has been demonstrated previously in patients with type 2 diabetes uncontrolled by oral antidiabetic drugs (OADs), GLP‐1RA therapy and basal insulin therapy in the phase 3 DUAL trials I to V .…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of IDegLira titrated once weekly versus twice weekly in patients with type 2 diabetes uncontrolled on oral antidiabetic drugs: DUAL VI randomized clinical trial

Harris

Kocsis

Prager

et al. 2017

AimsTo compare the safety and efficacy of a simpler titration algorithm for insulin degludec/liraglutide (IDegLira) with that used in previous DUAL trials in insulin‐naïve patients with type 2 diabetes.Research design and methodsThis 32‐week, open‐label, non‐inferiority trial randomized adults with type 2 diabetes uncontrolled on metformin ± pioglitazone to receive IDegLira, titrated either once weekly, based on the mean of 2 pre‐breakfast plasma glucose (PG) readings (n = 210), or twice weekly, based on the mean of 3 pre‐breakfast PG readings (n = 210).ResultsMean HbA1c decreased from 8.2% (65 mmol/mol) to 6.1% (43 mmol/mol) with once‐weekly titration and from 8.1% (65 mmol/mol) to 6.0% (42 mmol/mol) with twice‐weekly titration; non‐inferiority was confirmed (estimated treatment difference: 0.12% [−0.04; 0.28]95% CI, 1.30 mmol/mol [−0.41; 3.01]95% CI). Approximately 90% of patients achieved HbA1c < 7% in each arm. Mean fasting PG was similar after 32 weeks. Weight change was −1.0 kg vs −2.0 kg for once‐weekly vs twice‐weekly titration. Rates of severe or blood glucose‐confirmed symptomatic hypoglycaemia were low in both arms: 0.16 events/patient‐year of exposure (PYE) for once‐weekly, 0.76 events/PYE for twice‐weekly titration. Mean IDegLira dose at 32 weeks was 41 dose steps (41 U IDeg/1.48 mg Lira) for both arms. Overall adverse event rates were 207.8 and 241.3 events/100 PYE with once‐weekly and twice‐weekly titration, respectively.ConclusionA pragmatic titration algorithm with once‐weekly adjustments based on 2 PG readings resulted in a safety and glycaemic efficacy profile similar to that with twice‐weekly adjustments based on 3 preceding PG values in insulin‐naïve patients.

“…However, results from the AWARD-4 study are in line with results from the combination of GLP-1 RAs with insulin that was evaluated in a recent meta-analysis in comparison to a basal-bolus or basal-plus regimen (mean body weight difference, −3.72 kg). 19,25 In conclusion, at a lower total daily insulin dose, a larger proportion of patients, overall and across BMI subgroups, who were treated with once-weekly dulaglutide in combination with prandial insulin lispro achieved weight loss. All other studies compared either a flexible or fixed combination with basal insulin, showing a wide range of mean differences in weight, with large heterogeneity.…”

Section: Discussionmentioning

confidence: 88%

Weight loss in patients with type 2 diabetes receiving once‐weekly dulaglutide plus insulin lispro or insulin glargine plus insulin lispro: A post‐hoc analysis of the AWARD‐4 study across baseline body mass index subgroups

Fuechtenbusch¹,

Aberle

Heitmann

et al. 2019

Aims: Insulin-treated patients with type 2 diabetes (T2D) and obesity are challenged in achieving body weight stability or reduction, in addition to glycaemic control. Post-hoc analyses of body weight and insulin dose data from the AWARD-4 trial involved comparison of treatment with once-weekly dulaglutide 1.5 mg (N = 295) or 0.75 mg (N = 293) and treatment with daily insulin glargine (N = 296), each with prandial insulin lispro (± metformin).Materials and methods: Changes in weight and in the proportion of patients without weight gain or with weight loss of at least 3%, 5% or 10% or composites of HbA1c less than 7% without weight gain and weight loss of at least 3% after 52 weeks were compared between the dulaglutide (either dose) groups and the insulin glargine group, overall and by baseline BMI (<30, 30-<35, ≥35 kg/m 2 ), using analysis of covariance and logistic regression, including interaction terms. Results:The following parameters were statistically significant (P < 0.01) in favour of the dulaglutide-treated groups, at lower mean total daily insulin doses, vs the insulin glargine group.The achieved targets were more pronounced with dulaglutide 1.5 mg than with insulin glargine: LSM weight change difference, −3.23 kg; proportion of patients without weight gain, 49.0% vs 19.0%; proportion of patients with weight loss ≥3%, 21.7% vs 5.7% or with weight loss ≥5%, 10.5% vs 2.4%; proportion of patients with HbA1c <7% without weight gain, 26.2% vs 7.9%;proportion of patients with HbA1c <7% and weight loss ≥3%, 11.9% vs 1.4%, respectively. Treatment effect for these parameters was not significantly different across BMI categories.Conclusions: Larger proportions of patients in late-stage T2D needing treatment intensification achieved glycemic control without weight gain or with weight loss at lower insulin doses with once-weekly dulaglutide plus daily prandial insulin than with a basal-bolus insulin regimen, overall and across all three BMI subgroups.