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

Rodbard, Helena W.

doi:10.1089/dia.2018.0103

Cited by 23 publications

(9 citation statements)

References 63 publications

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“…This limits the rate and extent of meal-derived glucose presentation to b-cells, contributing to a predominant effect on postprandial glucose excursions, most markedly for the meal following administration 34 . Long-acting GLP-1 receptor agonists (such as semaglutide, albiglutide, dulaglutide, exenatide extended release, and liraglutide) predominantly lower blood glucose levels through stimulation of insulin secretion and reduction of glucagon levels, with a decreasing effect on gastric emptying over time likely due to tachyphylaxis [34][35][36] . This results in a lesser effect on PPG excursions compared with short-acting GLP-1 receptor agonists but a longer overall effect on glucose levels reducing FPG 34 .…”

Section: Rationale For Therapy Combining a Basal Insulin Analog And Amentioning

confidence: 99%

Rationale for a titratable fixed-ratio co-formulation of a basal insulin analog and a glucagon-like peptide 1 receptor agonist in patients with type 2 diabetes

Blonde

Anderson²,

Chava

et al. 2018

Current Medical Research and Opinion

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Objective: Achieving and maintaining recommended glycemic targets, including those for glycated hemoglobin A1c (A1C), is key to improving outcomes in patients with type 2 diabetes (T2D). As fasting plasma glucose and postprandial glucose contribute to overall A1C, targeting both is essential for sustaining glycemic control. Methods: This review examines the complementary mechanisms of action of glucagon-like peptide 1 (GLP-1) receptor agonists and basal insulin; they both enhance glucose-stimulated insulin release and suppress glucagon secretion. GLP-1 receptor agonists also slow gastric emptying and increase satiety. Results: Adding a GLP-1 receptor agonist to therapy with a basal insulin analog has been associated with improved overall glycemic control, with comparable risk of hypoglycemia and no weight gain. Titratable fixed-ratio co-formulations of basal insulin and a GLP-1 receptor agonist have been shown to improve glycemic control, with less complex dosing schedules, possibly increasing treatment adherence. The slow titration of fixed-ratio co-formulations has been shown to reduce the occurrence and severity of gastrointestinal adverse events associated with the use of a separate GLP-1 receptor agonist. Titratable fixed-ratio co-formulations also mitigate insulin-associated weight gain, and show a comparable risk of hypoglycemia to basal insulin use alone. Conclusions: The efficacy and safety of titratable fixed-ratio co-formulations have been demonstrated for insulin degludec/liraglutide and insulin glargine/lixisenatide in the DUAL and LixiLan trials, respectively, in both insulin-naive and -experienced patients. Titratable fixed-ratio co-formulations represent an attractive treatment option for many patients with T2D. ARTICLE HISTORY

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Section: Rationale For Therapy Combining a Basal Insulin Analog And Amentioning

confidence: 99%

Rationale for a titratable fixed-ratio co-formulation of a basal insulin analog and a glucagon-like peptide 1 receptor agonist in patients with type 2 diabetes

Blonde

Anderson²,

Chava

et al. 2018

Current Medical Research and Opinion

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“…has an advantage in controlling postprandial blood glucose. 31,32 Progressive failure of islet function and insulin resistance are considered to be the main pathological basis of T2DM. Long-term hyperglycemia and insulin resistance can cause atherosclerosis caused by damage to the vascular endothelium.…”

Section: Effect Of Liraglutide On Inflammationmentioning

confidence: 99%

Beneficial effects of liraglutide on peripheral blood vessels

et al. 2022

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Background/Aim. Macroangiopathy is the major cause of death and disability in type 2 diabetic patients. Studies have shown that liraglutide, a GLP-1 receptor agonist, can protect the cardiovascular system by inhibiting chronic inflammation of diabetes. However, the effects of liraglutide on peripheral blood vessels and peripheral blood leukocytes have not reported at home and abroad. Objective: To observe and explore vascular protection and mechanism of liraglutide in addition to hypoglycemic effect. Methods: 60 hospitalized patients with type 2 diabetes were recruited from December 2013 to December 2014 at the First Affiliated Hospital of Dalian Medical University. Before the treatment of liraglutide?height and weight were measure to calculate body mass index (BMI). Blood urea nitrogen (BUN) and so on were detected. Homeostasis model assessment of insulin resistance (HOMA-IR) and islet ? cell function (HOMA-?) were computed. After applying liraglutide for three months, all indexes were measured again. The effects of liraglutide on these indexes were analyzed by paired sample t test. Results: After treatment with liraglutide, HbA1c (8.46?1.62 vs 7.26?1.40%) and 2hPBG (11.95 vs 9.6 mmol/L) decreased significantly (P<0.05). Body weight (87.3 vs 82.5 kg) and BMI (30.37 vs 28.63 kg/m2) decreased by 5.5% and 5.7% (P<0.05). TG?2.57?1.54 vs 1.81?0.70 mmol/L? and LDL-C?2.92?0.78 vs 1.89?0.66 mmol/L?reduced significantly (P<0.05). ABI decreased from 1.24?0.10 to 1.14?0.06 cm/s by 8%, while baPWV decreased from 1442.15?196.26 to 1316.85?146.63 cm/s by 8.7%, and both difference was statistically significant (P < 0.001). Conclusion: Liraglutide, with a good hypoglycemic effect, can significantly reduce postprandial blood glucose and HbA1c, but can not significantly improve fasting plasma glucose, insulin resistance and islet function. It also significantly decreased body weight, BMI and TG. Liraglutide can significantly lower ba-PWV and ABI to protect peripheral blood vessels.

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“…The Harmony Outcomes CVOT of albiglutide is not considered in detail due to the withdrawal of this drug from the market in 2018 20 . CVOTs of short‐acting GLP‐1 RAs (once‐daily [QD] or twice‐daily [BID]) are not discussed here, considering that the most recent CVOTs belong to the QW formulations and such long‐acting drugs could improve patient adherence to therapies based on the convenience of drug administration 21‐24 . The review briefly mentions results from CVOTs relating to dipeptidyl peptidase‐4 inhibitors (DPP4is) and sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) to provide a comprehensive overview of this area, and as SGLT2is have been prominently discussed in the ADA guidelines.…”

Section: What Is Known and Objectivementioning

confidence: 99%

Cardiovascular safety outcomes of once‐weekly GLP‐1 receptor agonists in people with type 2 diabetes

Goldman

2020

J Clin Pharm Ther

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What is known and objective People with type 2 diabetes (T2D) are at increased risk of cardiovascular disease (CVD), which in turn is associated with increased morbidity and mortality. The impact of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on cardiovascular (CV) outcomes has been investigated in CV outcomes trials (CVOTs). This review aims to help pharmacists and other healthcare professionals (HCPs) gain a better understanding of such CVOTs in T2D with a primary focus on the once‐weekly (QW) GLP‐1 RAs. Methods This narrative review mainly focuses on the evaluation of the similarities and differences in the design and results of CVOTs involving currently approved and marketed QW GLP‐1 RAs—semaglutide subcutaneous, exenatide extended‐release (ER) and dulaglutide. Results from CVOTs of dipeptidyl peptidase‐4 inhibitors (DPP4is) and sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) are also included. Results and discussion Three CVOTs of QW GLP‐1 RAs were identified for inclusion in this review: SUSTAIN 6 (semaglutide), EXSCEL (exenatide ER) and REWIND (dulaglutide), all of which varied in terms of trial design, patient demographics and other baseline characteristics. Results from these CVOTs demonstrated the CV safety of QW GLP‐1 RAs compared with standard of care. Additionally, CV and renal benefits were demonstrated for semaglutide and dulaglutide, but not for exenatide ER. The CV safety of four DPP4is and three SGLT2is was demonstrated. None of the DPP4is had a CV or renal benefit, whereas all three SGLT2is were associated with CV and renal benefits. What is new and conclusion This article provides an overview of the results from QW GLP‐1 RA CVOTs, including the recently published results for dulaglutide, and places them within the broader T2D treatment landscape to help HCPs make informed decisions in daily practice. The QW GLP‐1 RAs with benefits reaching beyond glycaemic control can provide a comprehensive treatment option for people with T2D at high risk of CVD, with CVD or chronic kidney disease.

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

Cited by 23 publications

References 63 publications

Rationale for a titratable fixed-ratio co-formulation of a basal insulin analog and a glucagon-like peptide 1 receptor agonist in patients with type 2 diabetes

Rationale for a titratable fixed-ratio co-formulation of a basal insulin analog and a glucagon-like peptide 1 receptor agonist in patients with type 2 diabetes

Beneficial effects of liraglutide on peripheral blood vessels

Cardiovascular safety outcomes of once‐weekly GLP‐1 receptor agonists in people with type 2 diabetes

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