Exenatide twice daily versus glimepiride for prevention of glycaemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA): an open-label, randomised controlled trial

Gallwitz, Baptist; Guzmán, Juan Rosas; Dotta, Francesco; Guerci, Bruno; Simó, Rafael; Basson, Bruce R.; Festa, Andreas; Kiljański, Jacek; Sapin, Hélène; Trautmann, Michael E.; Schernthaner, Guntram

doi:10.1016/s0140-6736(12)60479-6

Cited by 137 publications

(120 citation statements)

References 29 publications

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“…However, exenatide resulted in significant weight reduction while SUs were weight neutral or resulted in weight gain [Derosa et al 2010[Derosa et al , 2011. Exenatide also demonstrated greater durability than glimepiride with fewer treatment failures (41% versus 54%) and longer duration before treatment failure (180 weeks versus 142 weeks) when added to metformin [Gallwitz et al 2012 [Pratley et al 2010]. In a 1-year extension of this trial, liraglutide maintained significant reductions in HbA1c, FBG, and body weight over sitagliptin [Pratley et al 2011].…”

Section: Short-acting Glp-1 Rasmentioning

confidence: 83%

Efficacy and tolerability of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus

Harris

McCarty

2014

Therapeutic Advances in Endocrinology

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Glucagon-like peptide-1 (GLP-1) has been evaluated for use in the treatment of type 2 diabetes mellitus (T2DM) due to its role in glucose regulation. Four GLP-1 receptor agonists (RAs) are currently indicated for T2DM in the USA. Exenatide and liraglutide are short-acting and require twice-daily and daily dosing, respectively. Two longer acting agents, exenatide long-acting release (LAR) and albiglutide, were formulated to allow for once-weekly dosing. All four GLP-1 RAs have demonstrated reductions in hemoglobin A1c, fasting blood glucose, and body weight both as monotherapy and in combination with first-and secondline diabetes agents including metformin, sulfonylureas, thiazolidinediones, and insulin. Greater glycemic control was seen with liraglutide compared with the other GLP-1 treatment options; however, the two long-acting agents were superior to exenatide twice daily. All agents were well tolerated with most adverse events being mild or moderate in nature. The most common adverse event was transient nausea which typically resolved 4-8 weeks after treatment initiation. Long-acting agents had lower rates of nausea but an increased incidence of injection site reactions. Trials have suggested GLP-1 RAs may improve cardiovascular risk factors including blood pressure, lipid parameters and inflammatory markers. Future trials are needed to confirm the clinical outcomes of these agents. Overall, GLP-1 RAs will provide benefit for patients with T2DM intolerable to or not reaching glycemic goals with first-line agents, especially in patients in need of weight loss.

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Section: Short-acting Glp-1 Rasmentioning

confidence: 83%

Efficacy and tolerability of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus

Harris

McCarty

2014

Therapeutic Advances in Endocrinology

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“…The NICE approach also may underestimate the risks of hypoglycemia and weight gain with sulfonylureas and risks of heart failure and fractures with glitazones. GLP-1 RAs, apart from producing durable and clinically meaningful reduction in HbA 1c , have several other advantages such as promotion of weight loss, reduction of blood pressure, and a favorable safety profile (with the exception of nausea and vomiting that wane with time) and may be beneficial at an earlier stage in the therapeutic algorithm (10,26,32,33,37, [76][77][78][79][80]. While some of the clinical trial data as well as the American Association of Clinical Endocrinologists (AACE) algorithm support early use of GLP-1 RAs, this may not be the preferred approach for all patients owing to high cost and the nature of injection therapy.…”

Section: Sglt2i: Adverse Effectsmentioning

confidence: 99%

Positioning SGLT2 Inhibitors/Incretin-Based Therapies in the Treatment Algorithm

2016

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S154Diabetes Care Volume 39, Supplement 2, August 2016 SGLT2 THERAPYsensitizer (6,7). GLP-1 is part of the physiological system signaling satiety (8,9), reduces food intake and promotes weight loss in humans (10), and delays gastric emptying (11). Early studies showed that continuous subcutaneous GLP-1 infusion effectively lowered fasting and postprandial glucose levels and promoted weight loss in patients with T2DM (12). However, endogenous human GLP-1 has a short half-life (2-3 min) due to breakdown in the circulation by protease enzymes, notably, dipeptidyl peptidase (DPP)-4, which cleaves the molecule to leave the inactive GLP-1 (9-36). Hence, native GLP-1 has limited therapeutic efficacy. Pharmaceutical development took two routes: inhibition of the DPP-4-degrading enzyme and prolongation of the biological half-life by developing DPP-4-resistant GLP-1 receptor agonists (GLP-1 RAs). DPP-4 InhibitorsFour oral DPP-4 inhibitors (DPP-4i) are approved for use in both the U.S. and the European Union (sitagliptin, saxagliptin, alogliptin, and linagliptin) ( Table 1). Vildagliptin is approved in the European Union but not the U.S. Several other agents of this class are marketed worldwide (for example, omaragliptin and trelagliptin are available only in Japan). All five DPP-4i appear to have similar efficacy in terms of glucose lowering. An 18-week, phase 3b, multicenter, double-blind trial of saxagliptin versus sitagliptin has demonstrated noninferiority as add-on therapy to metformin (13). Trelagliptin, a once-weekly DPP-4i, was studied against alogliptin once daily and has demonstrated noninferiority in the Japanese population studied (14). Meta-analysis of DPP-4i has shown an average HbA 1c reduction (20.74%) (15) that is slightly less efficacious than sulfonylureas when used as monotherapy and similar to metformin and pioglitazone (16) but inferior to GLP-1 RAs. DPP-4i can be used in combination with other oral agents or with basal insulin (17), although the reduction of HbA 1c with insulin is modest (18,19). The DPP-4i are weight neutral and have a low risk of hypoglycemia. DPP-4i: Adverse EffectsIn general, the adverse effect profile of the DPP-4i is quite favorable. With the exception of linagliptin, the DPP-4i require dose reduction in patients with renal impairment. Some concern has been raised about the risk of pancreatitis and pancreatic cancer, based on preclinical studies and reports from postmarketing surveillance studies. However, the current data do not support a likely association (20). The U.S. Food and Drug Administration (FDA) has recently issued a warning about the possibility of joint pain developing during DPP-4i treatment after review of 33 cases reported over the past 8 years. However, the potential mechanism(s) are uncertain and a causal link is unproven, although symptoms appear to resolve after treatment withdrawal (21). Several large cardiovascular (CV) outcome trials have been completed, comparing these agents with placebo on the background of standard diabetes care (Table 2), and have ...

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“…12 Newer classes of antidiabetic agents (thiazolidinediones, 17 GLP-1 agonists 18 or SGLT2 inhibitors 19 ) appear to have a more durable effect on HbA1c than SUs, however, implying superior long-term control of glycaemia.…”

Section: Durability Of Actionmentioning

confidence: 99%

This house believes that sulphonylureas should not be used routinely as second-line treatments for patients with type 2 diabetes

2016

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Exenatide twice daily versus glimepiride for prevention of glycaemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA): an open-label, randomised controlled trial

Cited by 137 publications

References 29 publications

Efficacy and tolerability of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus

Efficacy and tolerability of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus

Positioning SGLT2 Inhibitors/Incretin-Based Therapies in the Treatment Algorithm

This house believes that sulphonylureas should not be used routinely as second-line treatments for patients with type 2 diabetes

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