Consistent findings in glycaemic control, body weight and hypoglycaemia with <scp>iGlarLixi</scp> (insulin glargine/lixisenatide titratable fixed‐ratio combination) vs insulin glargine across baseline <scp>HbA1c</scp>, <scp>BMI</scp> and diabetes duration categories in the <scp>LixiLan‐L</scp> trial

Wysham, Carol; Bonadonna, Riccardo C.; Aroda, Vanita R.; Puig-Domingo, Manel; Kapitza, Christoph; Stager, William; Yu, Christine; Niemoeller, Elisabeth; Souhami, Elisabeth; Bergenstal, Richard M.

doi:10.1111/dom.12961

Cited by 24 publications

(28 citation statements)

References 19 publications

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“…Outcomes at Week 26 were included as potential predictors in this analysis because the definition of response was linked to achievement of the HbA1c goal (<7.0% [<53 mmol/mol]) at Week 26, the end of the core treatment period. In previous studies, baseline characteristics such as HbA1c were found to be strong predictors of response in some instances, although not consistently . In the current model, response at Week 26 was a stronger predictor than any baseline characteristics tested.…”

Section: Resultscontrasting

confidence: 60%

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Predictive factors associated with three years of response to HbA1c goals with exenatide QW or insulin glargine: Post‐hoc analysis of the DURATION‐3 study

Guerci

Trautmann²,

Lin

et al. 2019

Diabetes Obesity Metabolism

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This post-hoc analysis of the DURATION-3 study aimed to identify factors associated with sustained glycaemic response with exenatide once weekly (QW) or insulin glargine (IG) among patients with type 2 diabetes. Response was defined as achieving treatment target of HbA1c <7.0% (<53 mmol/mol) at Week 26; sustained responders maintained the treatment target for ≥80% of remaining visits, including one during the final 6 months. Of 467 patients, 287 (61.5%) completed 156 weeks of treatment. At Week 26, 175 patients (61.0%) (exenatide QW, n = 95; IG, n = 80) achieved an HbA1c response. At Week 156, 84 of 175 responders (48.0%) had sustained response, with more sustained responders with exenatide QW (22.7% vs 13.9% with IG; P < 0.03). Logistic regression identified three predictors of sustained response: (a) exenatide QW vs IG treatment (odds ratio, 2.584 [95% confidence interval, 1.288-5.187]; P = 0.0075), (b) lower HbA1c at Week 26 (0.139 [0.053-0.366]; P < 0.0001), and (c) lower fasting serum glucose at Week 26 (0.693 [0.541-0.888]; P = 0.0037). A regression model was used to estimate the likelihood of sustained response with either treatment. This analysis provides a helpful tool for predicting sustained response with exenatide QW or IG. K E Y W O R D S clinical trial, exenatide, GLP-1, glycaemic control, insulin therapy, type 2 diabetes

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Section: Resultscontrasting

confidence: 60%

“…In previous studies, baseline characteristics such as HbA1c were found to be strong predictors of response in some instances, 14,15 although not consistently. [16][17][18][19] In the current model, response at…”

Section: Resultsmentioning

confidence: 99%

Predictive factors associated with three years of response to HbA1c goals with exenatide QW or insulin glargine: Post‐hoc analysis of the DURATION‐3 study

Guerci

Trautmann²,

Lin

et al. 2019

Diabetes Obesity Metabolism

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show abstract

“…26 Patients treated with iGlarLixi showed reductions in HbA 1c of -1.1% and with iGlar of -0.6%. A higher percentage of patients achieved the HbA 1c target level of <7% (P < 0.0001): 55% of iGlarLixi patients reached HbA 1c <7% compared with 30% of iGlar patients.…”

Section: Lixisenatide/insulin Glargine Coformulationmentioning

confidence: 90%

The Clinical Impact of GLP-1 Receptor Agonists in Type 2 Diabetes: Focus on the Long-Acting Analogs

Rodbard¹

2018

Diabetes Technology & Therapeutics

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GLP-1 receptor agonists (GLP-1 RAs), introduced for clinical use in 2005, have excellent potency in reducing HbA 1c and mean glucose, improving fasting plasma glucose, inducing weight loss or protecting against the weight gain associated with insulin therapy, reducing appetite, and delaying gastric emptying. Two of these medications, liraglutide and semaglutide, appear to have cardioprotective effects as reflected in cardiovascular outcomes studies. The GLP-1 RAs are associated with gastrointestinal side effects that tend to diminish over time. They have very low risk of hypoglycemia unless used in conjunction with insulin or insulin secretagogues. Two coformulations of GLP-1 RAs together with long-acting basal insulin are available for daily use. The original GLP-1 RA, exenatide, requires twice-daily injections; two short-acting analogs are given once daily. Three currently available long-acting GLP-1 RAs are injected once weekly, providing greater convenience and potentially improving patient adherence. Semaglutide appears to be the most effective in terms of HbA 1c reduction and weight loss. GLP-1 RAs can be combined with all classes of antihyperglycemic agents except DPP-4 inhibitors. Current studies are exploring the use of an implantable osmotic pump for long-term administration of a rapid acting analog (exenatide), an oral preparation of semaglutide, benefits for management of obesity and nonalcoholic steatohepatitis, and mechanisms of cardioprotective effects.

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“…Mean body weight decreased in iGlarLixi recipients but increased in insulin glargine recipients (between‐group difference, 1.4 kg; P < 0.0001), and the number of hypoglycaemic events was similar in the two groups 53. In both studies, the improvement in glycaemic control with iGlarLixi vs the individual therapies was consistent regardless of baseline HbA 1c , BMI or diabetes duration 54, 55.…”

Section: Fixed‐ratio Formulationsmentioning

confidence: 84%

Use of glucagon‐like peptide‐1 receptor agonists among individuals on basal insulin requiring treatment intensification

Trautmann¹,

Vora

2018

Diabet. Med.

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As Type 2 diabetes progresses, treatment is intensified with additional therapies in an effort to manage hyperglycaemia effectively and therefore avoid complications. When greater efficacy is required, options for injectable treatments include glucagon‐like peptide‐1 receptor agonists and insulin, which may be added on to oral glucose‐lowering treatments. Among individuals receiving long‐acting basal insulin as their first injectable treatment, ~40−60% are unable to achieve or maintain their target HbA1c goals. For these people, treatment intensification options are relatively limited and include the addition of short‐acting prandial insulin or a glucagon‐like peptide‐1 receptor agonist. Glucagon‐like peptide‐1 receptor agonists vary in their effects, with short‐ and long‐acting agents having a greater impact on postprandial and fasting hyperglycaemia, respectively. Studies comparing treatment intensification options have found both glucagon‐like peptide‐1 receptor agonists and prandial insulin to be effective in reducing HbA1c concentrations; however, recipients of glucagon‐like peptide‐1 receptor agonists lost weight and had a greater frequency of gastrointestinal adverse events, whereas those receiving prandial insulin gained weight and had a greater incidence of hypoglycaemia. In addition to the separate administration of a glucagon‐like peptide‐1 receptor agonist and basal insulin, fixed‐ratio combinations of a glucagon‐like peptide‐1 receptor agonist and basal insulin offer a single administration for both treatments but have less flexibility in dose titration than treatment with their individual components. For individuals who require treatment intensification beyond basal insulin, use of these various options allows physicians to target the individual needs of their patients for the achievement of optimal long‐term glycaemic control.

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Consistent findings in glycaemic control, body weight and hypoglycaemia with iGlarLixi (insulin glargine/lixisenatide titratable fixed‐ratio combination) vs insulin glargine across baseline HbA1c, BMI and diabetes duration categories in the LixiLan‐L trial

Cited by 24 publications

References 19 publications

Predictive factors associated with three years of response to HbA1c goals with exenatide QW or insulin glargine: Post‐hoc analysis of the DURATION‐3 study

Predictive factors associated with three years of response to HbA1c goals with exenatide QW or insulin glargine: Post‐hoc analysis of the DURATION‐3 study

The Clinical Impact of GLP-1 Receptor Agonists in Type 2 Diabetes: Focus on the Long-Acting Analogs

Use of glucagon‐like peptide‐1 receptor agonists among individuals on basal insulin requiring treatment intensification

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