Five Weeks of Treatment with the GLP-1 Analogue Liraglutide Improves Glycaemic Control and Lowers Body weight in Subjects with Type 2 Diabetes

Nauck, Michael A.; Hompesch, Marcus; Filipczak, R.; Le, Teplinskaia; Zdravković, Milan; Gumprecht, Jakub

doi:10.1055/s-2006-924230

Cited by 127 publications

(93 citation statements)

References 11 publications

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“…These effects make GLP-1 a potent blood glucoselowering agent with multiple potential beneficial effects [14], potentially able to modulate the progression of Type 2 diabetes [15][16][17]. It is therefore of interest from the point of view of Type 2 diabetes therapy [16].Native GLP-1 is rapidly metabolized by dipeptidyl peptidase-4, which is found in multiple tissues and cell types, as well as in the circulation [18].…”

Section: Introductionmentioning

confidence: 99%

Effect of renal impairment on the pharmacokinetics of the GLP‐1 analogue liraglutide

Jacobsen

Hindsberger

Robson

et al. 2009

Brit J Clinical Pharma

194

127

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Patients with Type 2 diabetes are likely to have or to develop renal impairment, which affects the pharmacokinetics of some antidiabetic treatments.• Whether dosing of the once-daily human glucagon-like peptide-1 analogue liraglutide should be modified in patients with renal impairment has not previously been studied. WHAT THIS STUDY ADDS• Renal dysfunction was not found to increase the exposure of liraglutide. • Hence, no dose adjustment is expected to be required in patients with Type 2 diabetes and renal impairment treated with liraglutide. AIMSTo investigate whether dose adjustment of the once-daily human glucagon-like peptide-1 analogue liraglutide is required in patients with varying stages of renal impairment. METHODSA cohort of 30 subjects, of whom 24 had varying degrees of renal impairment and six had normal renal function, were given a single dose of liraglutide, 0.75 mg subcutaneously, and completed serial blood sampling for plasma liraglutide measurements for pharmacokinetic estimation. RESULTSNo clear trend for change in pharmacokinetics was evident across groups with increasing renal dysfunction. While the between-group comparisons of the area under the liraglutide concentrationcurve (AUC) did not demonstrate equivalence [estimated ratio AUCsevere/AUChealthy 0.73, 90% confidence interval (CI) 0.57, 0.94; and AUC (continuous ambulatory peritoneal dialysis)CAPD/AUChealthy 0.74, 90% CI 0.56, 0.97], the regression analysis of log(AUC) for subjects with normal renal function and mild-to-severe renal impairment showed no significant effect of decreasing creatinine clearance on the pharmacokinetics of liraglutide. The expected AUC ratio between the two subjects with the lowest and highest creatinine clearance in the study was estimated to be 0.88 (95% CI 0.58, 1.34) (NS). Degree of renal impairment did not appear to be associated with an increased risk of adverse events. CONCLUSIONSThis study indicated no safety concerns regarding use of liraglutide in patients with renal impairment. Renal dysfunction was not found to increase exposure of liraglutide, and patients with Type 2 diabetes and renal impairment should use standard treatment regimens of liraglutide. There is, however, currently limited experience with liraglutide in patients beyond mild-stage renal disease.

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Section: Introductionmentioning

confidence: 99%

Effect of renal impairment on the pharmacokinetics of the GLP‐1 analogue liraglutide

Jacobsen

Hindsberger

Robson

et al. 2009

Brit J Clinical Pharma

194

127

View full text Add to dashboard Cite

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“…No patient experienced hypoglycemic episodes (major or minor), and there was no treatment-related anti-liraglutide antibody induction (91). Treatment-related induction of antiliraglutide antibodies has not been observed in liraglutide studies to date (74,91).…”

Section: Liraglutidementioning

confidence: 88%

“…Finally, treatment using each dose of liraglutide was associated with significant declines in the proinsulin:insulin ratio. In a previous active comparator study, adjunctive treatment using liraglutide, titrated from 0.5 to 2.0 mg/day over 5 weeks, in tandem with metformin 1000 mg twice daily significantly reduced FG by 3.9 mmol/l (70 mg/dl; P!0.05) and HbA1c by 0.8% (P!0.05) compared with metformin monotherapy and significantly lowered FG by 1.2 mmol/l (22 mg/dl; P!0.05) and body weight by 2.9 kg (P!0.05 compared with metformin together with a sulfonylurea) (74).…”

Section: Liraglutidementioning

confidence: 98%

“…Incretin mimetics include exenatide (Byetta, Amylin Pharmaceuticals, San Diego, CA, USA; Eli Lilly), a 39-amino acid peptide amide previously termed AC2993 (60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72). Other incretin mimetics include the investigational agents liraglutide (73)(74)(75)(76)(77)(78), which is also known as NN2211 (Novo Nordisk, Bagsvaerd, Denmark), and a human recombinant GLP-1-albumin conjugate (known as albugon; GlaxoSmithKline, Human Genome Sciences) (79,80) and the GLP-1 receptor agonist ZP10 (Sanofi-Aventis, Bridgewater, NJ, USA), of which a prolonged-release formulation is being investigated.…”

Section: Overview Of Current and Emerging Therapies Exploiting The Enmentioning

confidence: 99%

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Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide 1 receptor agonists or insulin for patients with inadequate glycemic control?

Gaal¹,

Gutkin²,

Nauck³

2008

European Journal of Endocrinology

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Type 2 diabetes mellitus is associated with progressive decreases in pancreatic b-cell function. Most patients thus require increasingly intensive treatment, including oral combination therapies followed by insulin. Fear of hypoglycemia is a potential barrier to treatment adherence and glycemic control, while weight gain can exacerbate hyperglycemia or insulin resistance. Administration of insulin can roughly mimic physiologic insulin secretion but does not address underlying pathophysiology. Glucagon-like peptide 1 (GLP-1) is an incretin hormone released by the gut in response to meal intake that helps to maintain glucose homeostasis through coordinated effects on islet a-and b-cells, inhibiting glucagon output, and stimulating insulin secretion in a glucose-dependent manner. Biological effects of GLP-1 include slowing gastric emptying and decreasing appetite. Incretin mimetics (GLP-1 receptor agonists with more suitable pharmacokinetic properties versus GLP-1) significantly lower hemoglobin A1c, body weight, and postprandial glucose excursions in humans and significantly improve b-cell function in vivo (animal data). These novel incretin-based therapies offer the potential to reduce body weight or prevent weight gain, although the durability of these effects and their potential long-term benefits need to be studied further. This article reviews recent clinical trials comparing therapy with the incretin mimetic exenatide to insulin in patients with oral treatment failure, identifies factors consistent with the use of each treatment, and delineates areas for future research.European Journal of Endocrinology 158 773-784

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“…Incretin mimetics (GLP-1 agonists; exenatide, liraglutide) are given subcutaneously and have been shown in phase III trials to reduce fasting and postprandial glucose, improve insulin sensitivity, and reduce HbA1c [121,122] and are associated with modest but significant weight loss [123]. Adverse effects such as nausea appear to be mild and transient [121].…”

Section: Incretin Mimeticsmentioning

confidence: 99%

Current and novel therapies for the treatment of nonalcoholic steatohepatitis

Poorten

George

2007

Hepatol Int

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The worldwide epidemic of obesity and the metabolic syndrome has made nonalcoholic fatty liver disease (NAFLD), one of the most important liver diseases of our time. NAFLD is now the commonest cause of abnormal liver test results in industrialized countries and its incidence is rising. The current treatment of nonalcoholic steatohepatitis (NASH) has focused on lifestyle modification to achieve weight loss and modification of risk factors, such as insulin resistance, dyslipidemia, and hyperglycemia associated with the metabolic syndrome. With our increasing understanding of the pathogenesis of NASH, have come a plethora of new pharmacologic options with great potential to modify the natural history of NAFLD and NASH. This article focuses on a number of novel molecular targets for the treatment of NASH as well as the evidence for currently available therapy. It should be noted, however, that in part because of the long natural history of NASH and NAFLD, no therapy to date has been shown to unequivocally alter liver-related morbidity and mortality in these patients.

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Five Weeks of Treatment with the GLP-1 Analogue Liraglutide Improves Glycaemic Control and Lowers Body weight in Subjects with Type 2 Diabetes

Cited by 127 publications

References 11 publications

Effect of renal impairment on the pharmacokinetics of the GLP‐1 analogue liraglutide

Effect of renal impairment on the pharmacokinetics of the GLP‐1 analogue liraglutide

Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide 1 receptor agonists or insulin for patients with inadequate glycemic control?

Current and novel therapies for the treatment of nonalcoholic steatohepatitis

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