Day-long Subcutaneous Infusion of Exenatide Lowers Glycemia in Patients with Type 2 Diabetes

Taylor, Kristin; Kim, D.; Nielsen, Loretta L.; Aisporna, Maria; Baron, Alain; Fineman, Mark

doi:10.1055/s-2005-870529

Cited by 37 publications

(32 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients japanese patients with T2d were eligible for the tions were achieved within 6-7 weeks, and the mean plasma exenatide concentration was below the lower limit of the therapeutic range (50 pg/mL) [16] within 10 weeks after discontinuation of study drug.…”

Section: Methodsmentioning

confidence: 99%

“…Table 2 shows noncompartmental pharmacokinetic parameters for the pharmacokinetic evaluable population. Based on graphical evaluations of plasma exenatide trough concentrations, plasma exenatide concentrations reached 50 pg/mL, a concentration previously shown to significantly reduce plasma glucose [16], between Weeks 3-9 of the study for patients treated with exenatide QW 0.8 mg and between Weeks 2-5 of the study for patients treated with exenatide QW 2.0 mg. steady state, at which point the mean pharmacokinetic profiles began to flatten, was achieved by Week 8 for both exenatide QW groups (Figure 2). One patient receiving exenatide QW 0.8 mg was excluded from analyses on Day 1 because the plasma exenatide concentrations were below the quantification limits at all timepoints on that day.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

“…Plasma exenatide trough concentrations throughout the treatment period were evaluated graphically to determine the time to reach the lower limit of the therapeutic range (50 pg/mL) [16] and the time to reach steady state. additionally, key pharmacokinetic parameters were computed by noncompartmental methods: area under the concentration-versus-time curve of exenatide in the initial release period (auC [0-8 hours]) for day 1 (after a single subcutaneous injection), maximum observed plasma exenatide concentration (Cmax) for day 1, area under the concentration-versus-time curve of exenatide over a dosing interval at steady state for Weeks 9-10 (after QW dosing), and steadystate plasma exenatide concentration (Cave,ss) for QW 0.8 mg and exenatide QW 2.0 mg, respectively, during the treatment plus follow-up periods.…”

Section: Pharmacokinetic Evaluationsmentioning

confidence: 99%

See 2 more Smart Citations

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Exenatide Once Weekly in Japanese Patients with Type 2 Diabetes

et al. 2009

View full text Add to dashboard Cite

Abstract. This randomized, placebo-controlled, double-blind, parallel study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of exenatide once weekly (QW) in 30 japanese patients with type 2 diabetes (T2d) suboptimally controlled by diet and exercise alone or combined with biguanide, sulfonylurea, thiazolidinedione, or combinations of these agents (58.6% male; 58±9 years; body mass index 26.3±2.9 kg/m 2 ; hemoglobin a 1c [Hba 1c ] 7.4±0.8%; fasting plasma glucose [FPG] 156.1±29.1 mg/dL; duration of T2d 6±5 years; means ± sd). Patients were randomized in a 1:1:1 ratio to subcutaneous placebo QW, exenatide QW 0.8 mg, or exenatide QW 2.0 mg for 10 weeks. all evaluable patients were analyzed (placebo QW, n=10; exenatide QW 0.8 mg, n=10; exenatide QW 2.0 mg, n=9), unless otherwise stated. steady-state plasma exenatide concentrations were observed by Week 8 of the study. For the evaluable pharmacokinetic population, geometric mean (90% confidence interval) steady-state plasma concentrations (pg/mL) were 81.2 (68.3-96.4) and 344.5 (256.5-462.7) with exenatide QW 0.8 mg (n=8) and exenatide QW 2.0 mg (n=5), respectively. Baseline-to-Week 10 glycemic improvements with placebo QW, exenatide QW 0.8 mg, and exenatide QW 2.0 mg, respectively, were: Hba 1c (%): -0.4±0.3, -1.0±0.7, and -1.5±0.7; FPG (mg/dL): -20.5±20.4, -25.2±10.9, and -50.8±27.8; and 2-hour postprandial plasma glucose excursions (mg/dL): -8.8±26.9, -50.0±41.1, and -59.7±26.8 (means ± sd). No serious adverse events (aEs) were reported and no aEs led to study discontinuation in any group. The most frequent aE observed was mild-to-moderate injection site induration. No serious hypoglycemia was reported. Exenatide QW for 10 weeks was well tolerated and improved short-term glycemic control in japanese patients with suboptimally controlled T2d.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Pharmacodynamicsmentioning

confidence: 99%

Section: Pharmacokinetic Evaluationsmentioning

confidence: 99%

See 1 more Smart Citation

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Exenatide Once Weekly in Japanese Patients with Type 2 Diabetes

et al. 2009

View full text Add to dashboard Cite

show abstract

“…64,65 By week 6, exenatide onceweekly attained a maximum concentration higher than that attained by a single injection of exenatide 10 µg (a steady state concentration of 232 pg/mL versus 211 pg/mL). 59 Six weeks after stopping treatment, the serum concentration of exenatide once-weekly declined steadily to insignificant levels.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Exenatide once weekly: clinical outcomes and patient satisfaction

Jose¹,

Tahrani²,

Piya³

et al. 2010

PPA

View full text Add to dashboard Cite

Background: Type 2 diabetes mellitus (T2DM) is a complex disorder in which interactions between environmental and genetic factors result in the development of insulin resistance (in most cases) and progressive pancreatic β-cell failure. The currently available oral anti-diabetes treatments are effective as monotherapy; however, due to the progressive decline in β-cell function, most patients will require the use of combination therapy and eventually insulin to reach glycemic targets. These therapeutic options are not without undesirable side effects such as weight gain and hypoglycemia. Furthermore, T2DM is associated with impaired quality of life (QOL) and poor compliance with treatment. Hence, there is a need for anti-diabetes agents that result in sustained improvements in glycemic control without hypoglycemia or weight gain and have a positive impact on patients QOL and thereby hopefully improve compliance. Incretin-based therapy is the latest addition to anti-diabetes treatments which addresses some of the shortcomings of older treatments. Aims: To review the evidence for the use of exenatide once-weekly. Methods: We have searched Medline using the terms "exenatide", "exenatide once-weekly", and "exenatide LA". Results: Exenatide once-weekly is an incretin mimetic that is currently undergoing phase 3 clinical trials, and has been shown to improve glycemic parameters (HbA 1c and fasting and postprandial glucose levels), with low risk of hypoglycemia, causes weight loss, and use was associated with improvements in patient satisfaction which might have a positive impact on treatment compliance. Conclusions: Exenatide once-weekly is effective, well tolerated in patients with T2DM and should be a useful addition to the available range of anti-diabetes treatments.

show abstract

“…Based on graphical evaluations of plasma exenatide trough concentrations, plasma exenatide concentrations reached 50 pg/mL, a concentration previously shown to significantly reduce plasma glucose, 20 by week 2 for the 2.0 mg once weekly dose and by weeks 4-5 for the 0.8 mg once weekly dose (Fig. 1).…”

Section: Pharmacokinetics and Metabolismmentioning

confidence: 99%

The Current Status of Exenatide Once Weekly

Kulasa

2011

Clinical Medicine Insights: Therapeutics

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM) is a chronic, progressive metabolic disorder that is associated with long-term microvascular (retinopathy, neuropathy and nephropathy) and macrovascular (myocardial infarction, stroke, peripheral arterial disease) complications. Both the prevalence of T2DM and the cost of its long-term complications have driven the focus and emphasis on treatments aimed at reducing hyperglycemia and controlling hypertension and dyslipidemia while minimizing hypoglycemia and weight gain. Exenatide twice daily, the first GLP-1R agonist approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMEA), has been shown to reduce hemoglobin A1C, lower fasting and postprandial plasma blood glucose concentrations as well as reduce body weight without causing significant hypoglycemia. However, its current formulation requires twice daily subcutaneous injections and does not provide continuous GLP-1R activation. Therefore, a long-acting release form of exenatide has been developed for use as a once-weekly injection, providing for convenient administration and continuous GLP-1R activation. This review covers the currently published data on this new formulation including mechanism of action, pharmacokinetics, efficacy and comparison trials to other commonly used anti-diabetic agents.

show abstract

Day-long Subcutaneous Infusion of Exenatide Lowers Glycemia in Patients with Type 2 Diabetes

Cited by 37 publications

References 13 publications

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Exenatide Once Weekly in Japanese Patients with Type 2 Diabetes

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Exenatide Once Weekly in Japanese Patients with Type 2 Diabetes

Exenatide once weekly: clinical outcomes and patient satisfaction

The Current Status of Exenatide Once Weekly

Contact Info

Product

Resources

About