Glucagon-like Peptide-1 Receptor Agonists (GLP1-RA)

Alicic, Radica Z.; Cox, Emily J.; Neumiller, Joshua J.; Tuttle, Katherine R.

doi:10.1007/978-3-030-86020-2_26

Cited by 9 publications

(11 citation statements)

References 74 publications

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“…Accumulating evidence suggests that GLP-1 RAs (glucagon-like peptide-1 receptor agonists) may reduce the risk of stroke beyond their glycemic impact in people with T2D. [9][10][11][12][13][14] Currently, there are 5 available subcutaneous (SC) GLP-1 RAs (exenatide, lixisenatide, liraglutide, dulaglutide, and semaglutide) 15,16 and one oral formulation (once-daily oral semaglutide). 15 In a large metaanalysis of recent cardiovascular outcome trials, GLP-1 RAs were reported to reduce the risk of stroke significantly in people with T2D compared with placebo (hazard ratio [HR], 0.83 [95% CI, 0.76-0.92]; P=0.0002).…”

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confidence: 99%

“…[9][10][11][12][13][14] Currently, there are 5 available subcutaneous (SC) GLP-1 RAs (exenatide, lixisenatide, liraglutide, dulaglutide, and semaglutide) 15,16 and one oral formulation (once-daily oral semaglutide). 15 In a large metaanalysis of recent cardiovascular outcome trials, GLP-1 RAs were reported to reduce the risk of stroke significantly in people with T2D compared with placebo (hazard ratio [HR], 0.83 [95% CI, 0.76-0.92]; P=0.0002). 14 The American Heart Association/American Stroke Association as well as endocrinology and cardiology guidelines recommend the use of GLP-1 RAs with evidence of cardiovascular benefit for individuals at high/very high cardiovascular risk regardless of glycemic control to reduce the risk of future vascular events.…”

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confidence: 99%

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Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes: Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6

Strain

Frenkel

James

et al. 2022

Stroke

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Background: GLP-1 RA (glucagon-like peptide-1 receptor agonists), including semaglutide, may reduce stroke risk in people with type 2 diabetes. This post hoc analysis examined the subcutaneous and oral semaglutide effects, versus placebo, on stroke and its subtypes in people with type 2 diabetes at high cardiovascular risk. Methods: SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) and PIONEER 6 (Peptide Innovation for Early Diabetes Treatment) were randomized cardiovascular outcome trials of subcutaneous and oral semaglutide in people with type 2 diabetes at high cardiovascular risk, respectively. Time to first stroke and stroke subtypes were analyzed using a Cox proportional hazards model stratified by trial with pooled treatment as a factor. The impact of prior stroke, prior myocardial infarction or stroke, age, sex, systolic blood pressure, estimated glomerular filtration rate, and prior atrial fibrillation on treatment effects was assessed using interaction P values. Risk of major adverse cardiovascular event was analyzed according to prior stroke. Results: A total of 106/6480 participants had a stroke (1.0 event/100 patient-years of observation [PYO]). Semaglutide reduced incidence of any stroke versus placebo (0.8 versus 1.1 events/100 PYO; hazard ratio, 0.68 [95% CI, 0.46–1.00]; P =0.048), driven by significant reductions in risk of small-vessel occlusion (0.3 versus 0.7 events/100 PYO; hazard ratio, 0.51 [95% CI, 0.29–0.89]; P =0.017). Hazard ratios for risk of any stroke with semaglutide versus placebo were 0.60 (95% CI, 0.37–0.99; 0.5 versus 0.9 events/100 PYO) and 0.89 (95% CI, 0.47–1.69; 2.7 versus 3.0 events/100 PYO) in those without and with prior stroke, respectively. Except for prior atrial fibrillation ( P interaction =0.025), no significant interactions were observed between treatment effects on risk of any stroke and subgroups investigated, or between treatment effects on risk of major adverse cardiovascular event and prior stroke ( P interaction >0.05 for all). Conclusions: Semaglutide reduced incidence of any first stroke during the trials versus placebo in people with type 2 diabetes at high cardiovascular risk, primarily driven by small-vessel occlusion prevention. Semaglutide treatment, versus placebo, lowered the risk of stroke irrespective of prior stroke at baseline. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01720446 and NCT02692716.

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confidence: 99%

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confidence: 99%

Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes: Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6

Strain

Frenkel

James

et al. 2022

Stroke

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“…Currently available injectable agents in the United States are once-weekly exenatide, twice-daily exenatide, once-daily liraglutide, once-weekly semaglutide, once-weekly dulaglutide, and once-weekly tirzepatide 10. Of note, liraglutide is available alone or in a combination formulation with basal insulin (insulin degludec).…”

Section: Benefits Of Glp-1 Ra Therapymentioning

confidence: 99%

GLP-1 receptor agonists

Clark

2024

Jaapa

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Type 2 diabetes mellitus (T2DM) is a chronic medical condition affecting millions of individuals worldwide. The burden of disease is significant, as demonstrated by high morbidity and mortality and billions of healthcare dollars spent. The pathophysiology of T2DM is complex, with eight primary deficits. In recent years, an increased focus has been placed on incretin hormones, such as glucagon-like peptide-1 (GLP-1) for its glucose-lowering benefits. Several FDA-approved short-acting and long-acting GLP-1 receptor agonists (GLP-1 RAs) are available in the United States for the treatment of T2DM. These are liraglutide, exenatide, dulaglutide, and semaglutide, all administered via subcutaneous injection. Semaglutide is also available in an oral formulation. A newer dual glucose-dependent insulinotropic peptide (GIP) and GLP-1 RA, tirzepatide, is available as a subcutaneous injectable. In addition to improving glycemic control, GLP-1 RAs have been shown to lower total body weight, BP, and cholesterol as well as to improve renal function and beta-cell proliferation. These agents should be considered in every patient with T2DM due to their substantial clinical benefits and potential to help reduce disease burden.

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“…Still, insulin has some limitations, such as the risk of hypoglycaemia and increased body weight 1,4,5 . The gastrointestinal side effects of GLP‐1 RAs often lead to intolerability and subsequently a high discontinuation rate 6‐8 . Because of their complementary modes of action, the combination of basal insulin and GLP‐1RAs addresses the core pathophysiological defects in T2D and minimizes the adverse effects of the individual components 9 …”

Section: Introductionmentioning

confidence: 99%

iGlarLixi provides a higher derived time‐in‐range versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with type 2 diabetes: A post hoc analysis

Yang

Zhang

et al. 2023

Diabetes Obesity Metabolism

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Aim: To evaluate the efficacy of iGlarLixi in the Asian Pacific (AP) population with type 2 diabetes (T2D) using derived time-in-ranges calculated from seven-point selfmeasured blood glucose.Methods: Two phase III trials were analysed. LixiLan-O-AP was performed in insulinnaive T2D patients (n = 878) randomized to iGlarLixi, glargine 100 units/mL (iGlar) or lixisenatide (Lixi). LixiLan-L-CN was performed in insulin-treated T2D patients (n = 426) randomized to iGlarLixi or iGlar. Changes in derived time-in-ranges from baseline to end-oftreatment (EOT) and estimated treatment differences (ETDs) were analysed. The proportions of patients achieving 70% or higher derived time-in-range (dTIR), 5% or higher dTIR improvement, and the composite triple target (≥ 70% dTIR, < 4% derived time-below-therange [dTBR] and < 25% derived time-above-the-range [dTAR]) were calculated. Results:The changes from baseline to EOT in dTIR with iGlarLixi were greater versus iGlar (ETD 1 : 11.45% [95% CI, 7.66% to 15.24%]) or Lixi (ETD 2 : 20.54% [95% CI, 15.74% to 25.33%]) in LixiLan-O-AP, and versus iGlar (ETD: 16.59% [95% CI, 12.09% to 21.08%]) in LixiLan-L-CN. In LixiLan-O-AP, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT with iGlarLixi were 77.5% and 77.8%, respectively, higher than with iGlar (61.1% and 75.3%) or Lixi (47.0% and 53.0%). In LixiLan-L-CN, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT were 71.4% and 59.8% with iGlarLixi, greater than with iGlar (45.4% and 39.5%). More patients achieved the triple target with iGlarLixi compared with iGlar or Lixi. Conclusion: iGlarLixi achieved greater improvements in dTIR parameters versus iGlaror Lixi in insulin-naïve and insulin-experienced AP people with T2D.

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Glucagon-like Peptide-1 Receptor Agonists (GLP1-RA)

Cited by 9 publications

References 74 publications

Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes: Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6

Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes: Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6

GLP-1 receptor agonists

iGlarLixi provides a higher derived time‐in‐range versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with type 2 diabetes: A post hoc analysis

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