Once‐Weekly Exenatide: An Extended‐Duration Glucagon‐Like Peptide Agonist for the Treatment of Type 2 Diabetes Mellitus

Minze, Molly G.; Klein, Mary S.; Jernigan, Michelle J.; Wise, Stephen; Frugé, Kristian S.

doi:10.1002/phar.1240

Cited by 10 publications

(4 citation statements)

References 22 publications

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“…Long-acting exenatide is formulated in microspheres of poly-(d,l-lactide- co -glycolide) for once-weekly administration [19]. Liraglutide is another long-acting GLP-1RA that is administered once daily.…”

Section: Structure and Physiology Of Glucagon-like Peptide-1 (Glp-1)mentioning

confidence: 99%

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in the Brain–Adipocyte Axis

Geloneze

Lima-Júnior

Velloso

2017

Drugs

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The complexity of neural circuits that control food intake and energy balance in the hypothalamic nuclei explains some of the constraints involved in the prevention and treatment of obesity. Two major neuronal populations present in the arcuate nucleus control caloric intake and energy expenditure: one population co-expresses orexigenic agouti-related peptide (AgRP) and neuropeptide Y and the other expresses the anorexigenic anorectic neuropeptides proopiomelanocortin and cocaine- and amphetamine-regulated transcript (POMC/CART). In addition to integrating signals from neurotransmitters and hormones, the hypothalamic systems that regulate energy homeostasis are affected by nutrients. Fat-rich diets, for instance, elicit hypothalamic inflammation (reactive activation and proliferation of microglia, a condition named gliosis). This process generates resistance to the anorexigenic hormones leptin and insulin, contributing to the genesis of obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have increasingly been used to treat type 2 diabetes mellitus. One compound (liraglutide) was recently approved for the treatment of obesity. Although most studies suggest that GLP-1RAs promote weight loss mainly due to their inhibitory effect on food intake, other central effects that have been described for native GLP-1 and some GLP-1RAs in rodents and humans encourage future clinical trials to explore additional mechanisms that potentially underlie the beneficial effects observed with this drug class. In this article we review the most relevant data exploring the mechanisms involved in the effects of GLP-1RAs in the brain–adipocyte axis.

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Section: Structure and Physiology Of Glucagon-like Peptide-1 (Glp-1)mentioning

confidence: 99%

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in the Brain–Adipocyte Axis

Geloneze

Lima-Júnior

Velloso

2017

Drugs

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“…Exending is a GLP-1 peptide analogue discovered from the salive of guila monster, which display GLP-1 agonism pharmacologic effect, and currently marketed as a pos-prandial injection or a once-a-week or once-a-month formulation in polymeric microparticles (Liu et al, 2010;Minze et al, 2013;Pinelli and Hurren, 2011). An adverse reaction observed with exendin therapy is pancreatite (Aroda and DeYoung, 2011;Ryan et al, 2013a), and without the cardiovascular benefits observed with liraglutide.…”

Section: Introductionmentioning

confidence: 99%

Sustained release and pharmacologic evaluation of human glucagon-like peptide-1 and liraglutide from polymeric microparticles

Icart

Souza

Lima

2019

Journal of Microencapsulation

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The GLP-1 class of peptide agonists has been shown to exert regulatory key roles in both diabetes, obesity and related complications. Given the short half-life of GLP-1 its use has been historically discouraged. We developed polymeric microparticles loaded with either human GLP-1 (7-37) or liraglutide peptides by double emulsion and solvent evaporation approach. The size distribution of all formulations was of about 30-50 μm. The in vitro kinetic release assays showed a sustained release of the peptides extending up to 30 to 40 days with varying profiles. Morphologic analysis demonstrated a more regular particle surface for those comprising polymers PLA, PLA-PEG and PLGA. In vivo evaluation in Swiss male mice demonstrated a similar extension of effect of decreasing in body weight gain for up to 25 days after a single subcutaneous administration of either hGLP-1 or liraglutide peptide-loaded microparticles (200 µg peptide / kg body weight) compared to controls. These demonstrate the effectiveness of hGLP-1 as a therapeutic agent in long-term, continuous release from peptide-load microparticles, and thus its plausibility as an unmodified therapeutic agent.

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“…Patients initiating OW GLP-1RAs, including semaglutide, were twice as likely to achieve all clinical outcomes of interest (HbA 1c and/or weight-loss goals) compared with those initiating DPP-4i. These outcomes from the comparator analysis are aligned with previous RCTs and real-world studies [ 19 , 26 – 29 ]. The DURATION-2 trial demonstrated greater mean HbA 1c reduction (− 1.5% vs. − 0.9%) and weight loss (− 2.3 kg vs. − 1.5 kg) in patients treated with exenatide OW compared with sitagliptin (a DPP-4i).…”

Section: Discussionmentioning

confidence: 64%

Real-World Effectiveness of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists (OW GLP-1RAs) in Comparison with Dipeptidyl Peptidase-4 Inhibitors (DPP-4is) for Glycemic Control and Weight Outcomes in Type 2 Diabetes Mellitus (RELATE)

Tan,

Divino,

Amamoo

et al. 2024

Clin Drug Investig

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Background The efficacy of once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1RAs) has been established in several trials in people with type 2 diabetes mellitus (T2DM); however, real-world evidence on their effectiveness is limited. This study evaluated the effectiveness of OW GLP-1RA regarding glycemic and weight outcomes, and relative to DPP-4i in a comparator analysis. Methods This observational cohort study evaluated glycated hemoglobin (HbA 1c ) and weight outcomes in people with T2DM with two or more prescription claims for the same OW GLP-1RA using a pre-post study design (including for a semaglutide OW T2DM subgroup, hereafter referred to as semaglutide). Comparator analysis for the same outcome was performed for OW GLP-1RAs versus DPP-4i and semaglutide subgroup versus DPP-4i. A linked patient population from the IQVIA PharMetrics ® Plus database and the Ambulatory Electronic Medical Records (AEMR) database was analyzed using data from January 2017 to April 2022. HbA 1c and weight were assessed at baseline and at the end of the 12-month post-index period. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline patient characteristics in the comparator analysis. Results In the pre-post analysis, a greater numerical reduction in HbA 1c and weight was observed for the semaglutide subgroup ( N = 354) relative to the OW GLP-1RA cohort ( N = 921). In the semaglutide subgroup, 52.5% and 34.2% of patients achieved HbA 1c of < 7.0% and ≥ 5% weight loss, respectively. For the comparator analysis, the OW GLP-1RAs ( N = 651) were significantly more effective ( p < 0.001) in reducing HbA 1c (− 1.5% vs. − 1.0%) and weight (− 3.2 kg vs. − 1.0 kg) than the DPP-4is ( N = 431). Similarly, the semaglutide cohort ( N = 251) also displayed more effectiveness ( p < 0.001) in reducing HbA 1c (− 1.7% vs. − 0.9%) and weight (− 4.1 kg vs. − 1.3 kg) than the respective DPP-4i cohort ( N = 417). Patients initiating OW GLP-1RAs, including the semaglutide cohort, were at least twice as likely to achieve HbA 1c and weight outcomes as well as composite outcomes compared with those initiating DPP-4is. Conclusion The study reinforces that OW GLP-1RAs are more effective in glycemic control and weight reduction compared with DPP-4is in people with T2DM in the real-world setting. These findings align with the recommendation in the current guidelines for utilizing glucose-lowering treatment regimens that support weight-management goals in people with T2DM. ...

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Once‐Weekly Exenatide: An Extended‐Duration Glucagon‐Like Peptide Agonist for the Treatment of Type 2 Diabetes Mellitus

Cited by 10 publications

References 22 publications

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in the Brain–Adipocyte Axis

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in the Brain–Adipocyte Axis

Sustained release and pharmacologic evaluation of human glucagon-like peptide-1 and liraglutide from polymeric microparticles

Real-World Effectiveness of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists (OW GLP-1RAs) in Comparison with Dipeptidyl Peptidase-4 Inhibitors (DPP-4is) for Glycemic Control and Weight Outcomes in Type 2 Diabetes Mellitus (RELATE)

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