Lower rates of cardiovascular events and mortality associated with liraglutide use in patients treated with basal insulin: A DEVOTE subanalysis (DEVOTE 10)

Brown‐Frandsen, Kirstine; Emerson, Scott S.; McGuire, Darren K.; Pieber, Thomas R.; Poulter, Neil; Pratley, Richard E.; Zinman, Bernard; Ranthe, Mattis F.; Grøn, Randi; Lange, Marc; Moses, Alan C.; Őrsy, Petra; Buse, John B.

doi:10.1111/dom.13677

Cited by 13 publications

(12 citation statements)

References 19 publications

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“…A recent subgroup analysis of the DEVOTE trial showed a reduced risk of MACE in patients using liraglutide in combination with basal insulin compared with patients using basal insulin without liraglutide, over a median follow‐up of 2 years . Adding further support to our results, this analysis also showed a non‐significant trend for a reduced risk of severe hypoglycaemia, and slightly lower mean bolus insulin dose in patients with concomitant liraglutide use …”

Section: Discussionsupporting

confidence: 83%

“…13 Adding further support to our results, this analysis also showed a non-significant trend for a reduced risk of severe hypoglycaemia, and slightly lower mean bolus insulin dose in patients with concomitant liraglutide use. 13…”

Section: Discussionsupporting

confidence: 80%

“…In contrast to the present analysis, a higher rate of confirmed hypoglycaemia was reported when adding liraglutide compared with placebo to basal insulin in that trial, but the authors suggested that this may have resulted from a lack of insulin dose adjustment at the time of liraglutide initiation . A recent subgroup analysis of the DEVOTE trial showed a reduced risk of MACE in patients using liraglutide in combination with basal insulin compared with patients using basal insulin without liraglutide, over a median follow‐up of 2 years . Adding further support to our results, this analysis also showed a non‐significant trend for a reduced risk of severe hypoglycaemia, and slightly lower mean bolus insulin dose in patients with concomitant liraglutide use …”

Section: Discussioncontrasting

confidence: 67%

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Long‐term efficacy and safety of combined insulin and glucagon‐like peptide‐1 therapy: Evidence from the LEADER trial

Tack¹,

Jacob

Desouza

et al. 2019

Diabetes Obesity Metabolism

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Aim Glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) and insulin combination therapy is an effective treatment option for type 2 diabetes, but long‐term data are lacking. The aim was to assess the long‐term efficacy of the GLP‐1RA liraglutide in subgroups by insulin use in the LEADER trial. Materials and Methods LEADER assessed cardiovascular (CV) safety and efficacy of liraglutide (1.8 mg) versus placebo (plus standard of care therapy) in 9340 patients with type 2 diabetes and high risk of CV disease, for up to 5 years. We analyzed CV events, metabolic parameters and hypoglycaemia post hoc in three subgroups by baseline insulin use (basal‐only insulin, other insulin or no insulin). Insulin was a non‐random treatment allocation as part of standard of care therapy. Results At baseline, 5171 (55%) patients were not receiving insulin, 3159 (34%) were receiving basal‐only insulin and 1010 (11%) other insulins. Insulin users had a longer diabetes duration and slightly worse glycaemic control (HbA1c) than the no‐insulin subgroup. Liraglutide reduced HbA1c and weight versus placebo in all three subgroups (P < .001), and severe hypoglycaemia rate in the basal‐only insulin subgroup. The need for insulin was less with liraglutide. CV risk reduction with liraglutide was similar to the main trial results in the basal‐only and no‐insulin subgroups. Conclusions In patients on insulin, liraglutide improved glycaemic control, weight and need for insulin versus placebo, for at least 36 months with no increased risk of severe hypoglycaemia, while maintaining CV safety/efficacy, supporting the combination of liraglutide and insulin for management of type 2 diabetes.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 80%

Section: Discussioncontrasting

confidence: 67%

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Long‐term efficacy and safety of combined insulin and glucagon‐like peptide‐1 therapy: Evidence from the LEADER trial

Tack¹,

Jacob

Desouza

et al. 2019

Diabetes Obesity Metabolism

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“…22,23 Degludec demonstrated non-inferiority to IGlar U100 22 and liraglutide in reducing the risk of major adverse cardiovascular events compared with placebo. 23 Furthermore, post hoc sub-analyses of the DEVOTE 24 and DUAL programme 25 were in agreement with these findings, suggesting that cardiovascular safety was preserved.…”

Section: Apy (Insulin Glargine 100 Units/ml [Iglar U100] + Insulin Asmentioning

confidence: 62%

IDegLira improves patient‐reported outcomes while using a simple regimen with fewer injections and dose adjustments compared with basal–bolus therapy

Miller¹,

Doshi²,

Grøn

et al. 2019

Diabetes Obesity Metabolism

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Aims Basal–bolus therapy is associated with greater treatment burden and lower adherence compared with more simplified regimens. This post hoc analysis studied the difference between insulin degludec/liraglutide (IDegLira) and basal–bolus therapy on number of injections, dose adjustments and patient outcomes in the DUAL VII trial. Materials and methods DUAL VII was a 26‐week, open‐label trial in which patients with uncontrolled type 2 diabetes who were using metformin and insulin glargine 100 units/mL (20–50 U) were randomized 1:1 to IDegLira (N = 252) or basal–bolus (insulin glargine U100 + insulin aspart ≤4 times/day) (N = 254). This post hoc analysis reports the observed mean number of injections and cumulative dose adjustments during 26 weeks of treatment. Patient‐reported outcomes (Treatment‐Related Impact Measure – Diabetes [TRIM‐D] and Short Form‐36 Health Survey version 2 [SF‐36v2]) were collected at scheduled visits and change from baseline scores calculated. Results The clinical benefits (non‐inferior HbA1c reductions, weight benefit, less hypoglycaemia) of IDegLira vs basal–bolus therapy were achieved with fewer cumulative dose adjustments (16.6 vs 217.2, respectively) and fewer injections (1 vs ≥3 per day, respectively). Patients treated with IDegLira experienced significant improvements across all TRIM‐D domains compared with those undergoing basal–bolus therapy. The SF‐36v2 showed improvements in both treatment arms with no significant difference between arms in the physical component summary, but there was a significant improvement in patients treated with IDegLira in the mental component summary (P = .0228). Conclusions These findings, combined with the DUAL VII results, suggest that IDegLira, through a more simplified regimen versus basal–bolus therapy, may help improve patient adherence and improve patient outcomes related to diabetes management, treatment burden and mental health, which in turn may assist in the timely achievement of glycaemic control in clinical practice.

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“…DEVOTE demonstrated that degludec was non-inferior to glargine with respect to the incidence of major CV events (MACE) in participants with T2D at high risk for CV events (n = 7637) [33]. A post hoc analysis of participants in DEVOTE, which compared outcomes between participants concomitantly treated with liraglutide with those who had no liraglutide use, found that participants treated with degludec or IGlar U100 with liraglutide had significantly fewer MACE compared with participants in the degludec/IGlar U100 without liraglutide group (hazard ratio [HR] 0.62, 95% CI 0.41; 0.92; p = 0.02 [71]). This observation suggested that liraglutide might have CV benefits for people treating their T2D with basal insulin.…”

Section: Cardiovascular (Cv) Safetymentioning

confidence: 99%

Clinical Considerations When Initiating and Titrating Insulin Degludec/Liraglutide (IDegLira) in People with Type 2 Diabetes

Harris

Abrahamson

Ceriello

et al. 2020

Drugs

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Therapeutic inertia is a substantial obstacle to the initiation of insulin therapy in people with uncontrolled type 2 diabetes (T2D). This effect has in part been perpetuated by concerns over the impact of a burdensome regimen and the increased risk of hypoglycemia and body weight gain often associated with insulin use. An effective, yet simple, less burdensome regimen with a lower risk of body weight gain and hypoglycemia compared with an insulin-only regimen, may help to address these concerns more effectively. We review the available clinical and real-world data on IDegLira, a once-daily, injectable, fixedratio combination of insulin degludec (degludec) and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide, in people with T2D. Evidence from the comprehensive DUAL clinical trial program suggests an advantage of IDegLira over traditional insulin therapies in a number of clinical outcomes, including maintenance of glycemic control, achievement of glycemic targets, reducing the risk of hypoglycemia, and body weight loss. These findings were demonstrated in participants with T2D irrespective of prior GLP-1RA and insulin use. Furthermore, the individual components of IDegLira have confirmed safety (degludec) or significant benefit in terms of improvement of cardiovascular risk (liraglutide). As an injectable therapy that is simple to titrate, IDegLira has the potential to optimize the ability to achieve relevant glycemic targets, and offers a suitable treatment option for people with T2D requiring insulin therapy who are at risk of hypoglycemia or weight gain.

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Lower rates of cardiovascular events and mortality associated with liraglutide use in patients treated with basal insulin: A DEVOTE subanalysis (DEVOTE 10)

Cited by 13 publications

References 19 publications

Long‐term efficacy and safety of combined insulin and glucagon‐like peptide‐1 therapy: Evidence from the LEADER trial

Long‐term efficacy and safety of combined insulin and glucagon‐like peptide‐1 therapy: Evidence from the LEADER trial

IDegLira improves patient‐reported outcomes while using a simple regimen with fewer injections and dose adjustments compared with basal–bolus therapy

Clinical Considerations When Initiating and Titrating Insulin Degludec/Liraglutide (IDegLira) in People with Type 2 Diabetes

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