Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study

Drucker, Daniel J.; Buse, John B.; Taylor, Kristin; Kendall, David M.; Trautmann, Michael E.; Zhuang, Dongliang; Porter, Lisa

doi:10.1016/s0140-6736(08)61206-4

Cited by 951 publications

(1,328 citation statements)

References 36 publications

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“…The principal effects of GLP‐1 receptor agonists are to induce pancreatic insulin secretion, slow gastric emptying, and suppress postprandial glucagon secretion 15, 34, 35, 36, 37. Since increases in t max and t 1/2b of the gastric emptying rate were observed in the lixisenatide group vs the sitagliptin group, it is likely that slowing of gastric emptying was the driver for PPG reduction in this study, rather than insulinotropic effects.…”

Section: Discussionmentioning

confidence: 83%

Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study)

Yamada

Senda

Naito

et al. 2017

Diabetes Obesity Metabolism

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AimTo evaluate the pharmacodynamics of lixisenatide once daily vs sitagliptin once daily in Japanese patients with type 2 diabetes receiving insulin glargine U100.Materials and methodsThis multicentre, open‐label, phase IV study (NEXTAGE Study; ClinicalTrials.gov number, NCT02200991) randomly assigned 136 patients to either lixisenatide once daily via subcutaneous injection (10 µg initially increased weekly by 5 up to 20 µg) or once‐daily oral sitagliptin 50 mg. The primary endpoint was the change in postprandial glucose (PPG) exposure 4 hours after a standardized breakfast (PPG area under the plasma glucose concentration–time curve [AUC0 :00‐4:00h]) from baseline to day 29.ResultsLixisenatide reduced PPG exposure to a statistically significantly greater extent than sitagliptin: least squares (LS) mean change from baseline in PPG AUC0 :00‐4:00h was −347.3 h·mg/dL (−19.3 h·mmol/L) in the lixisenatide group and −113.3 h·mg/dL (−6.3 h·mmol/L) in the sitagliptin group (LS mean between‐group difference −234.0 h·mg/dL [−13.0 h·mmol/L], 95% confidence interval −285.02 to −183.00 h·mg/dL [−15.8 to −10.2 h·mmol/L]; P < .0001). Lixisenatide led to significantly greater LS mean reductions in maximum PPG excursion than sitagliptin (−122.4 vs −46.6 mg/dL [−6.8 vs −2.6 h·mmol/L]; P < .0001). Change‐from‐baseline reductions in exposure to C‐peptide, fasting glycoalbumin levels, and the gastric emptying rate were greater in the lixisenatide than in the sitagliptin group. The incidence of treatment‐emergent adverse events was higher with lixisenatide (60.9%) than with sitagliptin (16.4%), with no serious events or severe hypoglycaemia reported.ConclusionLixisenatide reduced PPG significantly more than sitagliptin, when these agents were added to basal insulin glargine U100, and was well tolerated.

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Section: Discussionmentioning

confidence: 83%

Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study)

Yamada

Senda

Naito

et al. 2017

Diabetes Obesity Metabolism

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“…Once‐weekly exenatide has been shown to improve glycaemic control in a glucose‐dependent manner, with a low risk of hypoglycaemia, in people with type 2 diabetes 10. The extended‐release delivery method, glucose‐dependent effects on insulin and glucagon,11 and improved postprandial glucose (PPG) control observed with once‐weekly exenatide12 are proposed to lead to less glycaemic variability, although studies specifically designed to evaluate glycaemic variability with once‐weekly exenatide treatment have been limited.…”

Section: Introductionmentioning

confidence: 99%

Exenatide once weekly improved 24‐hour glucose control and reduced glycaemic variability in metformin‐treated participants with type 2 diabetes: a randomized, placebo‐controlled trial

Frías

Nakhle²,

Ruggles

et al. 2016

Diabetes Obesity Metabolism

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AimTo assess the effects of once‐weekly exenatide on 24‐hour glucose control and variability.Materials and methodsThis double‐blind, placebo‐controlled trial randomized metformin‐treated adults with type 2 diabetes to once‐weekly exenatide 2.0 mg or placebo. Continuous glucose monitoring (CGM) was performed at baseline and weeks 4 and 10. The primary outcome was change in CGM‐measured 24‐hour mean glucose level.ResultsIn the once‐weekly exenatide (n = 60) and placebo (n = 56) groups (modified intention‐to‐treat population), the baseline glycated haemoglobin (HbA1c) concentrations were 8.2% and 8.0%, respectively, and the fasting plasma glucose (FPG) concentration was 9.86 and 9.32 mmol/L, respectively. Once‐weekly exenatide significantly (p < 0.001) reduced 24‐hour mean glucose level versus placebo (week 4, −1.44 vs −0.29 mmol/L; week 10, −1.71 vs −0.17 mmol/L), with consistent control throughout the week. Once‐weekly exenatide significantly reduced FPG and 2‐hour postprandial glucose (PPG) levels versus placebo at week 4 (FPG, −1.65 vs −0.11 mmol/L; PPG, −1.79 vs −0.11 mmol/L) and week 10 (FPG, −2.32 vs −0.28 mmol/L; PPG, −2.46 vs −0.33 mmol/L). At week 10, once‐weekly exenatide reduced the mean amplitude of glucose excursions (MAGE; −0.84 vs 0.16 mmol/L) and standard deviation (s.d.) of mean glucose (−0.35 vs 0.04 mmol/L). By week 10, once‐weekly exenatide‐treated participants spent more time in euglycaemia (once‐weekly exenatide, 77% vs placebo, 58%), less time in hyperglycaemia (22% vs 42%), and a similar time in hypoglycaemia (0.7% vs 0.3%). Common adverse events were injection‐site nodule (once‐weekly exenatide, 10.0% vs placebo, 0.0%), urinary tract infection (6.7% vs 8.9%) and nausea (6.7% vs 0.0%).ConclusionsIn metformin‐treated participants with type 2 diabetes, once‐weekly exenatide significantly improved daily glucose control and reduced glycaemic variability at weeks 4 and 10, as shown by reductions in 24‐hour glucose, FPG and PPG levels, MAGE and s.d., and increased time spent in euglycaemia.

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“…Postprandial glucagon release is reduced and postprandial insulin release is enhanced 30; however, these GLP‐1RAs are less available during fasting states and are therefore less effective for reducing fasting measures. In contrast, for the long‐acting GLP‐1RAs exenatide once weekly, liraglutide, albiglutide and dulaglutide, effects on gastric emptying are not as strong as their short‐acting counterparts 31 or decline over time 32, probably as a result of the continuous GLP‐1RA exposure causing tachyphylaxis 33, leading to less pronounced PPG reductions 34. Instead, these agents appear to reduce HbA 1c concentration through sustained increase in fasting insulin 34, suppression of fasting glucagon 31, and subsequently lower fasting glucose levels.…”

Section: Effects Of Glp‐1ra Treatmentmentioning

confidence: 96%

“…Given that short‐acting GLP‐1RAs tend to exhibit greater postprandial control than long‐acting GLP‐1RAs 31, short‐acting GLP‐1RAs may be an appropriate choice for individuals on basal insulin exhibiting a postprandial glycaemic deficit. In contrast, long‐acting GLP‐1RAs may offer greater benefit to individuals requiring improvements in fasting glycaemic control.…”

Section: Treatment Intensification Of Basal Insulin With Glp‐1rasmentioning

confidence: 99%

Use of glucagon‐like peptide‐1 receptor agonists among individuals on basal insulin requiring treatment intensification

Trautmann¹,

Vora

2018

Diabet. Med.

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As Type 2 diabetes progresses, treatment is intensified with additional therapies in an effort to manage hyperglycaemia effectively and therefore avoid complications. When greater efficacy is required, options for injectable treatments include glucagon‐like peptide‐1 receptor agonists and insulin, which may be added on to oral glucose‐lowering treatments. Among individuals receiving long‐acting basal insulin as their first injectable treatment, ~40−60% are unable to achieve or maintain their target HbA1c goals. For these people, treatment intensification options are relatively limited and include the addition of short‐acting prandial insulin or a glucagon‐like peptide‐1 receptor agonist. Glucagon‐like peptide‐1 receptor agonists vary in their effects, with short‐ and long‐acting agents having a greater impact on postprandial and fasting hyperglycaemia, respectively. Studies comparing treatment intensification options have found both glucagon‐like peptide‐1 receptor agonists and prandial insulin to be effective in reducing HbA1c concentrations; however, recipients of glucagon‐like peptide‐1 receptor agonists lost weight and had a greater frequency of gastrointestinal adverse events, whereas those receiving prandial insulin gained weight and had a greater incidence of hypoglycaemia. In addition to the separate administration of a glucagon‐like peptide‐1 receptor agonist and basal insulin, fixed‐ratio combinations of a glucagon‐like peptide‐1 receptor agonist and basal insulin offer a single administration for both treatments but have less flexibility in dose titration than treatment with their individual components. For individuals who require treatment intensification beyond basal insulin, use of these various options allows physicians to target the individual needs of their patients for the achievement of optimal long‐term glycaemic control.

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Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study

Cited by 951 publications

References 36 publications

Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study)

Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study)

Exenatide once weekly improved 24‐hour glucose control and reduced glycaemic variability in metformin‐treated participants with type 2 diabetes: a randomized, placebo‐controlled trial

Use of glucagon‐like peptide‐1 receptor agonists among individuals on basal insulin requiring treatment intensification

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