Pronounced reduction of postprandial glucagon by lixisenatide: a meta‐analysis of randomized clinical trials

Åhrén, Bo; Gautier, Jean‐François; Berria, Rachele; Stager, William; Aronson, Ronnie; Bailey, Clifford J.

doi:10.1111/dom.12290

Cited by 27 publications

(39 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Baseline HbA1c was the characteristic most closely associated with a glycemic response to saxagliptin. This is consistent with findings that higher baseline HbA1c is associated with a greater reduction in HbA1c with DPP-4 inhibitors [21,24] and other oral antidiabetes medications [25]. HOMA-2%β values can be a functional result (insulin secretion stimulated pharmacologically) rather than a biological improvement in β-cell functionality.…”

Section: Discussionsupporting

confidence: 89%

Saxagliptin Responder Analysis: A Pooled Analysis of 5 Clinical Trials

Sjöstrand¹,

Leibowitz²

2016

J Diabetes Metab

View full text Add to dashboard Cite

Objective: To assess the treatment response of patients with T2DM to saxagliptin at 24 weeks based on their initial response to saxagliptin at 12 weeks.Methods: Data were pooled from five 24-week, randomized, placebo-controlled trials of saxagliptin. Patients (N=1994) were categorized by change in glycated hemoglobin (HbA1c) after 12 weeks of saxagliptin treatment as responders (HbA1c decrease ≥ 0.5%; 61% of saxagliptin-treated patients), intermediate responders (HbA1c decrease ≥ 0.2% and <0.5%; 14% of patients), and nonresponders (HbA1c decrease <0.2%; 25% of patients). [-4.8%, 5.6%]). Baseline characteristics that were associated with glycemic response to saxagliptin included higher baseline HbA1c (P<0.0001), higher HOMA-2%β (P<0.0001), lower fasting insulin (P=0.0006), shorter T2DM duration (P=0.033), and male sex (P=0.031). Results Conclusion:Responders, who comprised 61% of saxagliptin-treated patients analyzed, derived significant benefit from saxagliptin, with a ~1% decline in HbA1c and increased β-cell function at 24 weeks compared with nonresponders.

show abstract

Section: Discussionsupporting

confidence: 89%

Saxagliptin Responder Analysis: A Pooled Analysis of 5 Clinical Trials

Sjöstrand¹,

Leibowitz²

2016

J Diabetes Metab

View full text Add to dashboard Cite

show abstract

“…An important evidence for this was the demonstration that subjects with type 2 diabetes had higher baseline glucagon levels than non-diabetic subjects and these levels were not suppressed by a carbohydrate meal, as was the case in the non-diabetics [47]. The hyperglucagonemia in type 2 diabetes which is less suppressible by raising glucose has been confirmed in many studies [48] and is clearly evident by the correlation in improvement in glycemia and reduction in glucagon by dipeptidyl peptidase-4 (DPP-4) inhibition [49] and GLP-1 receptor agonism [50]. We have also in our long-term population study in Malmö evaluated the contribution of perturbations in glucagon secretion for changes in glucose tolerance.…”

Section: Glucagon Is An Important Player In Diabetesmentioning

confidence: 99%

“…This has been enforced by the successful improvement of hyperglycemia by DPP-4 inhibition and GLP-1 receptor agonism in association with reduction in glucagon [49,50]. The first demonstration that GLP-1 reduces glucagon diabetes was presented by Gutniak et al, who showed that GLP-1 infusion in subjects with type 2 diabetes reduced glucagon levels after meal ingestion ( Fig.…”

Section: Glucagon Is a Target For Treatment Of Diabetesmentioning

confidence: 99%

Glucagon – Early breakthroughs and recent discoveries

Åhrén

2015

Peptides

View full text Add to dashboard Cite

“…Lixisenatide significantly decreases HbA 1c and postprandial glucose when used as monotherapy or add-on therapy [210][211][212][213][214][215][250][251][252][253][254][255][256][257] . In a meta-analysis of RCTs, compared with placebo, lixisenatide treatment produced reductions in 2 h postprandial glucose from baseline (LSMD −4.9 mmol/l, P <0.001), glucose excursion (LSMD −4.5 mmol/l, P <0.001) and postprandial glucagon (LSMD −19.0 ng/l, P <0.001) 256 .…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

2016

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.

show abstract

Pronounced reduction of postprandial glucagon by lixisenatide: a meta‐analysis of randomized clinical trials

Cited by 27 publications

References 42 publications

Saxagliptin Responder Analysis: A Pooled Analysis of 5 Clinical Trials

Saxagliptin Responder Analysis: A Pooled Analysis of 5 Clinical Trials

Glucagon – Early breakthroughs and recent discoveries

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Contact Info

Product

Resources

About