Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes

Wysham, Carol; Rosenstock, Julio; Vetter, Marion L.; Dong, Fang; Iqbal, Nayyar

doi:10.1111/dom.13056

Cited by 29 publications

(30 citation statements)

References 16 publications

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“…tide BID; however, SMPG data showed this differential effect on prandial glucose with exenatide BID only after specific meals following drug administration 26. Moreover, these results are not consistent with the meal tolerance test performed in DURATION-NEO-1 (exenatide QW autoinjector vs. exenatide BID), where there was no significant difference between treatments in premeal glucose values or postmeal excursion 27. In another meal tolerance test study assessing lixisenatide versus liraglutide, lixisenatide had a larger reduction in 4-hour postbreakfast area under the glucose curves compared with liraglutide 28.…”

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confidence: 69%

Relative contribution of basal and postprandial hyperglycaemia stratified by HbA1c categories before and after treatment intensification with dulaglutide

Umpiérrez

Pantalone

Atisso

et al. 2019

Diabetes Obesity Metabolism

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Aim: To assess the effect of dulaglutide on the relative contribution of basal hyperglycaemia (BHG) and postprandial hyperglycaemia (PPHG) to overall hyperglycaemia across HbA1c categories in patients with type 2 diabetes.Methods: Data from five phase 3 studies (N = 673) were pooled to assess the change in relative contributions of BHG and PPHG to overall hyperglycaemia across different HbA1c categories after 6 months of treatment intensification with dulaglutide 1.5 mg as monotherapy or with 1 or 2 oral medication(s) in patients with type 2 diabetes. BHG and PPHG were calculated using the area under the curve (AUC) of 7-point self-monitored plasma glucose concentration profiles. As a secondary objective, relative contribution of BHG and PPHG for dulaglutide versus liraglutide, exenatide BID and insulin glargine was assessed by individual studies at 6 months. Results: In pooled data, after 6 months of treatment intensification with dulaglutide 1.5 mg, there was a significant reduction from baseline in overall hyperglycaemia (AUC overall ) [(mean ± SE) -466.31 ± 18.32 mg*h/dL (P < 0.001)], BHG (AUC basal ) [(mean ± SE) -371.46 ± 16.36 mg*h/dL (P < 0.001)] and PPHG (AUC postprandial ) [(mean ± SE) -94.84 ± 7.97 mg*h/dL (P < 0.001)]. At baseline, relative contributions of BHG increased and PPHG decreased with increasing HbA1c levels. This pattern was maintained at 6 months, even as overall glycaemia improved with decreasing HbA1c values. Conclusions: In patients with type 2 diabetes, dulaglutide reduces HbA1c by lowering both basal and postprandial hyperglycaemia across various HbA1c levels. K E Y W O R D S basal insulin, dulaglutide, GLP-1 RAs, glycaemic control, type 2 diabetes 1 | INTRODUCTION Widely accepted treatment guidelines recommend an individualized treatment approach towards target HbA1c for patients with type 2 diabetes, based upon cardiovascular disease, life expectancy, disease duration, comorbidities, micro-and macrovascular complications, adherence and other patient-related factors. 1-4 HbA1c is a measure of overall glucose exposure during both fasting and postprandial state, and this interrelationship between the "glucose triad" of HbA1c, fasting glucose and postprandial glucose level changes with progression of the disease. 5 Monnier et al., in a study of 290 patients with type 2 diabetes managed with diet, metformin and/or sulphonylurea, showed that the relative contribution of postprandial hyperglycaemia (PPHG) decreases with increase in HbA1c and the relationship is the opposite for relative contribution of basal hyperglycaemia (BHG) to overall hyperglycaemia. 6 Moreover, the relative contribution of BHG and PPHG to overall hyperglycaemia in patients across a range of HbA1c levels of 7.3-10.2% (56.3-83.0 mmol/mol) was~50%, highlighting the need for drugs that impact both BHG and PPHG for a large proportion of patients. 6 In another study conducted by Riddle et al., in patients with mean baseline HbA1c of 8.7% (71.6 mmol/mol) treated with insulin glargine, the mean relative contribution of BHG t...

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confidence: 69%

Relative contribution of basal and postprandial hyperglycaemia stratified by HbA1c categories before and after treatment intensification with dulaglutide

Umpiérrez

Pantalone

Atisso

et al. 2019

Diabetes Obesity Metabolism

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“…Discrepancy with our study is probably attributable to the different definition of discontinuation. A possible reason for higher discontinuation rates with ExeOW compared with liraglutide is the formation of subcutaneous nodules, which occurred more frequently with the first than with the newest ExeOW injection device …”

Section: Discussionmentioning

confidence: 99%

Comparative effectiveness of exenatide once‐weekly versus liraglutide in routine clinical practice: A retrospective multicentre study and meta‐analysis of observational studies

Fadini

Bonora

Lapolla

et al. 2019

Diabetes Obesity Metabolism

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In this study, we retrospectively compared the effectiveness of exenatide once‐weekly (ExeOW) versus liraglutide in non‐insulin treated patients with type 2 diabetes followed under routine care. We also present a meta‐analysis of similar observational studies available in the literature. In our multicentre retrospective study, patients initiating ExeOW ( n = 204) or liraglutide ( n = 410) had similar baseline clinical characteristics. Change in HbA1c at 6 months was superimposable in the two groups (−0.7% ± 1.0%), and changes in body weight were also similar (ExeOW ‐2.2 ± 3.7 kg; liraglutide −2.5 ± 4.3 kg; p = 0.457). Discontinuation rates were numerically but not significantly lower for ExeOW versus liraglutide. Pooling these data with those of observational studies available in the literature yielded superimposable effects between the two groups for the change in HbA1c and body weight, with a higher risk of discontinuation (mainly based on pharmacy refill rates) for ExeOW. We conclude that, in patients under routine care, initiation of ExeOW provides similar benefits on HbA1c and body weight as initiation of liraglutide. These data help view the results of randomized controlled trials from the perspective of their application in routine clinical practice.

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“…In clinical studies with exenatide QWS, there were no new safety findings observed with the formulation when compared to studies conducted with exenatide QW (Blevins et al, ; Drucker et al, ; Gadde et al, ; Wysham et al, ). A study in moderately overweight subjects with type 2 diabetes mellitus reported no adverse effects following 90 days treatment with MCT oil at 18 g day −1 (equivalent to 1575 mg kg −1 week −1 in an 80 kg human) (Han et al, ).…”

Section: Discussionmentioning

confidence: 93%

Nonclinical safety and pharmacokinetics of Miglyol 812: A medium chain triglyceride in exenatide once weekly suspension

Buss¹,

Ryan²,

Baughman³

et al. 2018

J of Applied Toxicology

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Exenatide, a glucagon-like peptide-1 receptor agonist was originally developed as either a twice daily or once weekly injectable therapeutic for patients with type 2 diabetes. Exenatide QW suspension was developed for use with an autoinjector device, in which the microspheres are suspended in Miglyol 812, a mixture of medium chain triglycerides (MCTs). MCTs are a class of lipids whose fatty acid chains contain from six to 12 carbon atoms (medium chain fatty acids or MCFAs). While MCTs are edible oils present in many foods, including foodstuffs containing coconut and palm kernel oils, limited information is available regarding the oral and subcutaneous bioavailability of MCTs as well as safety following subcutaneous injection. These studies were designed to investigate the non-clinical pharmacokinetics and safety of MCTs. In a single dose pharmacokinetic study, MCFAs were rapidly detected in the plasma of rats following oral administration of either Miglyol 812 or tricaprylin at doses of 10 or 9.48 g kg , respectively. Following subcutaneous dosing with Miglyol 812, MCFAs were rapidly absorbed with a similar profile to that following oral dosing. Furthermore, the toxicity of Miglyol 812 alone was evaluated in a 3 month repeat dose toxicology studies in cynomolgus monkeys. In this study, weekly subcutaneous doses of 0.15 g kg did not elicit any treatment-related effects in cynomolgus monkeys. In conclusion, these studies alongside the available literature data show that Miglyol 812 is a safe excipient for use in subcutaneously administered therapeutics.

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Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes

Cited by 29 publications

References 16 publications

Relative contribution of basal and postprandial hyperglycaemia stratified by HbA1c categories before and after treatment intensification with dulaglutide

Relative contribution of basal and postprandial hyperglycaemia stratified by HbA1c categories before and after treatment intensification with dulaglutide

Comparative effectiveness of exenatide once‐weekly versus liraglutide in routine clinical practice: A retrospective multicentre study and meta‐analysis of observational studies

Nonclinical safety and pharmacokinetics of Miglyol 812: A medium chain triglyceride in exenatide once weekly suspension

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