Insulin treatment and longer diabetes duration both predict poorer glycaemic response to liraglutide treatment in type 2 diabetes: the Association of British Clinical Diabetologists Nationwide Liraglutide Audit

Thong, Ken; McGowan, Barbara; Htay, Thein Thein; Pernet, A; Kelly, Chris; Rajeswaran, Chinnadorai; Howell, Jill; Duncan, Catriona; Inkster, Berit; Buchanan, Linda; Kassim, Saiful; Nayer, Rahul; Barwell, N. J.; Walton, Christopher; Ryder, Robert E.; contributors, Abcd Nationwide Liraglutide Audit

doi:10.15277/bjdvd.2015.046

Cited by 6 publications

(7 citation statements)

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“…These lower proportions could be explained by the high mean baseline HbA1c in our study, which has previously been identified as a significant predictor of achieving HbA1c targets in response to liraglutide [22]. Response may also be influenced by duration of diabetes; our results indicated a poorer response to the glycemic reduction and control targets with increased duration, a finding consistent with the Association of British Clinical Diabetologists Nationwide Liraglutide Audit [23]. …”

Section: Discussionsupporting

confidence: 87%

Effectiveness of Liraglutide and Lixisenatide in the Treatment of Type 2 Diabetes: Real-World Evidence from The Health Improvement Network (THIN) Database in the United Kingdom

et al. 2017

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IntroductionThe glucagon-like peptide-1 receptor agonists liraglutide and lixisenatide are effective at reducing glycated hemoglobin (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM). Although liraglutide has demonstrated superior efficacy in head-to-head clinical trials, real-world evidence of comparative effectiveness is lacking. This observational study aimed to assess the effectiveness of liraglutide versus lixisenatide in UK clinical practice.MethodsElectronic medical records from The Health Improvement Network (THIN) UK primary care database were analyzed. Patients aged ≥18 years, diagnosed with T2DM, and prescribed liraglutide or lixisenatide between 01 May 2013 and 31 December 2015 were included in the study. Adjusted linear regression models compared the difference in mean change in HbA1c, body mass index (BMI), and systolic blood pressure (SBP) after 12-month follow-up. The proportion of patients achieving glycemic control (HbA1c <6.5%, <7.0%, <7.5%); HbA1c reduction >1%; and weight reduction ≥3% within 12 months were determined. Cox proportional hazards modeling was used to evaluate the effect of treatment on time to achieving HbA1c and weight reduction targets. Healthcare resource use (HCRU) (GP, secondary care, hospitalizations) was compared using analysis of covariance.ResultsThe primary outcome was assessed in 579 liraglutide and 213 lixisenatide new users. Fully adjusted linear regression indicated that liraglutide reduced HbA1c significantly more than lixisenatide (mean treatment difference −0.30; 95% CI −0.56, −0.04; p = 0.025). Compared to lixisenatide, liraglutide recipients were 2.5 times more likely to achieve HbA1c <6.5% (p = 0.0002). Liraglutide users were also more likely to achieve HbA1c <7.0% (HR 2.10; p < 0.0001), <7.5% (HR 1.65; p < 0.0001), and >1% HbA1c reduction (HR 1.29; p = 0.0002). BMI and SBP reductions were greater for the liraglutide group but results were not significant. HCRU was comparable between treatment groups.ConclusionThese results from the THIN database indicate that liraglutide treatment provided better outcomes related to glycemic control.FundingNovo Nordisk.

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Section: Discussionsupporting

confidence: 87%

Effectiveness of Liraglutide and Lixisenatide in the Treatment of Type 2 Diabetes: Real-World Evidence from The Health Improvement Network (THIN) Database in the United Kingdom

et al. 2017

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“…Both clinical and demographic factors have been identified as potential predictors of response to therapy, including age at diagnosis, duration of diabetes, baseline insulin dose, baseline glycated haemoglobin (HbA1c), body mass index (BMI), lipid levels, renal function, sex, geographical region, and ethnicity 5‐9 . Particular concerns with regard to response to glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have been duration of diabetes, glucose control and insulin dose, all of which, when greater, might suggest less islet β‐cell reserve or reduced function 10,11 . Furthermore, there is evidence to suggest a lower risk of hypoglycaemia in people with higher BMI, 12,13 so any advantage of GLP‐1RAs over insulin might then be ameliorated.…”

Section: Introductionmentioning

confidence: 99%

“… 5 , 6 , 7 , 8 , 9 Particular concerns with regard to response to glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have been duration of diabetes, glucose control and insulin dose, all of which, when greater, might suggest less islet β‐cell reserve or reduced function. 10 , 11 Furthermore, there is evidence to suggest a lower risk of hypoglycaemia in people with higher BMI, 12 , 13 so any advantage of GLP‐1RAs over insulin might then be ameliorated.…”

Section: Introductionmentioning

confidence: 99%

Findings for iGlarLixi versus BIAsp 30 confirmed in groups of people with type 2 diabetes with different biomedical characteristics

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McCrimmon

Rosenstock

et al. 2022

Diabetes Obesity Metabolism

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Aim: To report prespecified and post hoc analyses of the SoliMix dataset exploring the impact of baseline participant characteristics on the original SoliMix study outcomes, to enable informed treatment choices for people with different biomedical characteristics.Methods: SoliMix (EudraCT 2017-003370-13) compared once-daily iGlarLixi (a fixedratio combination of insulin glargine 100 U/mL and the glucagon-like peptide-1 receptor agonist lixisenatide) with twice-daily BIAsp 30 (30% insulin aspart and 70% insulin aspart protamine). In this analysis, the original primary outcomes of noninferiority of iGlarLixi versus BIAsp 30 in terms of glycated haemoglobin (HbA1c) change and superiority in terms of body weight change, together with change in basal insulin dose and hypoglycaemia outcomes, were investigated by baseline age, duration of diabetes, insulin dose, HbA1c level, body mass index (BMI), and renal function.Results: No evidence of difference in comparative treatment effect was detected across baseline age, duration of diabetes, insulin dose, HbA1c level, BMI and renal function subgroups for any endpoint (all heterogeneity P > 0.05), except American Diabetes Association Level 2 hypoglycaemia event rate when stratified by insulin dose (P = 0.011), which may be a chance difference given multiple testing and the small numbers of Level 2 events.Conclusions: Treatment effects of iGlarLixi were consistent irrespective of baseline HbA1c, insulin dose, BMI, age, duration of diabetes and renal function, supporting the use of iGlarLixi as an efficacious and well-tolerated treatment option in people with type 2 diabetes with a wide range of biomedical characteristics.This article has an accompanied Plain Language Summary in the Supporting Information Data S1.

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“…One of the mechanisms through which GLP-1 RAs achieve glycemic control is stimulation of β-cell insulin secretion [89]; as such, it follows that GLP-1 RA treatment in patients with marked β-cell failure will not achieve sufficient insulin secretion, thereby reducing the efficacy of this approach in patients with more advanced disease. Indeed, studies have shown that longer duration of diabetes and severe insulin deficiency is associated with reduced efficacy of longer-acting GLP-1 RAs [90–92], which is especially important in older adults who may have longstanding disease. With this in mind, the combination of a GLP-1 RA with basal insulin remains a logical approach to T2D treatment, based on the complementary effects of these two agents.…”

Section: Rationale For Combination Therapy Comprising Glp-1 Ras and Bmentioning

confidence: 99%

Combining GLP-1 Receptor Agonists and Basal Insulin in Older Adults with Type 2 Diabetes: Focus on Lixisenatide and Insulin Glargine

2019

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Estimates suggest that there are currently 122.8 million adults 65-99 years of age living with diabetes, of whom 90-95% are diagnosed with type 2 diabetes (T2D). Over the past two decades, a greater understanding of the complex and multifactorial pathogenesis of T2D has resulted in the development and introduction of new-generation classes of glucose-lowering therapies, which are now extensively endorsed by prevailing guidelines and are increasingly being used worldwide. These newer agents may further assist in the effective pharmacological management of T2D through the provision of patient-centered care that acknowledges multimorbidity and is respectful of and responsive to individual patient preferences and barriers. Given these considerations, the therapeutic approach in older patients with T2D is complex, particularly in those who have functional dependence, frailty, dementia, or who are at end-of-life. It is currently too early to draw conclusions on the long-term use of newer glucose-lowering agents in this population, as their efficacy and safety in older adults remains largely unknown. In this review, we will discuss considerations for the use of glucose-lowering treatments in older adults, with particular focus on the use of basal insulin and glucagon-like peptide-1 receptor agonists, and the rationale for the use of combination therapy comprising these agents. Finally, we will review clinical data from studies of the fixed-ratio combination of insulin glargine and lixisenatide in older patients with T2D.

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Insulin treatment and longer diabetes duration both predict poorer glycaemic response to liraglutide treatment in type 2 diabetes: the Association of British Clinical Diabetologists Nationwide Liraglutide Audit

Cited by 6 publications

References 16 publications

Effectiveness of Liraglutide and Lixisenatide in the Treatment of Type 2 Diabetes: Real-World Evidence from The Health Improvement Network (THIN) Database in the United Kingdom

Effectiveness of Liraglutide and Lixisenatide in the Treatment of Type 2 Diabetes: Real-World Evidence from The Health Improvement Network (THIN) Database in the United Kingdom

Findings for iGlarLixi versus BIAsp 30 confirmed in groups of people with type 2 diabetes with different biomedical characteristics

Combining GLP-1 Receptor Agonists and Basal Insulin in Older Adults with Type 2 Diabetes: Focus on Lixisenatide and Insulin Glargine

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