A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management

New England Journal of Medicine, Journal Year: 2015, Volume and Issue: 373(1), P. 11 - 22

Published: July 1, 2015

Obesity is a chronic disease with serious health consequences, but weight loss difficult to maintain through lifestyle intervention alone. Liraglutide, glucagon-like peptide-1 analogue, has been shown have potential benefit for management at once-daily dose of 3.0 mg, injected subcutaneously.We conducted 56-week, double-blind trial involving 3731 patients who did not type 2 diabetes and had body-mass index (BMI; the in kilograms divided by square height meters) least 30 or BMI 27 if they treated untreated dyslipidemia hypertension. We randomly assigned 2:1 ratio receive subcutaneous injections liraglutide mg (2487 patients) placebo (1244 patients); both groups received counseling on modification. The coprimary end points were change body proportions losing 5% more than 10% their initial weight.At baseline, mean (±SD) age was 45.1±12.0 years, 106.2±21.4 kg, 38.3±6.4; total 78.5% women 61.2% prediabetes. At week 56, group lost 8.4±7.3 kg weight, those 2.8±6.5 (a difference -5.6 kg; 95% confidence interval, -6.0 -5.1; P<0.001, last-observation-carried-forward imputation). A 63.2% as compared 27.1% (P<0.001), 33.1% 10.6%, respectively, (P<0.001). most frequently reported adverse events mild moderate nausea diarrhea. Serious occurred 6.2% 5.0% group.In this study, liraglutide, an adjunct diet exercise, associated reduced improved metabolic control. (Funded Novo Nordisk; SCALE Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.).

Language: Английский

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Glucagon-like peptide 1 (GLP-1)

Molecular Metabolism, Journal Year: 2019, Volume and Issue: 30, P. 72 - 130

Published: Sept. 30, 2019

Background: The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential.Among the numerous metabolic effects of GLP-1 are glucose-dependent stimulation insulin secretion, decrease gastric emptying, inhibition food intake, increase natriuresis and diuresis, modulation rodent b-cell proliferation.GLP-1 also has cardio-and neuroprotective effects, decreases inflammation apoptosis, implications for learning memory, reward behavior, palatability.Biochemically modified enhanced potency sustained action, receptor agonists successfully in clinical use treatment type-2 diabetes, several GLP-1-based pharmacotherapies evaluation obesity.Scope review: In this review, we provide detailed overview on nature its pharmacology discuss therapeutic various diseases.Major conclusions: Since discovery, emerged as pleiotropic myriad functions that go well beyond classical identification an incretin hormone.The beneficial render interesting candidate development to treat obesity, neurodegenerative disorders

Language: Английский

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Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1

Cell Metabolism, Journal Year: 2018, Volume and Issue: 27(4), P. 740 - 756

Published: April 1, 2018

Language: Английский

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3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

The Lancet, Journal Year: 2017, Volume and Issue: 389(10077), P. 1399 - 1409

Published: Feb. 23, 2017

Language: Английский

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The Discovery and Development of Liraglutide and Semaglutide

Frontiers in Endocrinology, Journal Year: 2019, Volume and Issue: 10

Published: April 12, 2019

The discovery of glucagon-like peptide-1 (GLP-1), an incretin hormone with important effects on glycemic control and body weight regulation, led to efforts extend its half-life make it therapeutically effective in people type 2 diabetes (T2D). development short- then long-acting GLP-1 receptor agonists (GLP-1RAs) followed. Our article charts the analogs liraglutide and, subsequently, semaglutide. We examine chemistry employed designing semaglutide, human nonhuman studies used investigate their cellular targets pharmacological effects, ongoing investigations into new applications formulations these drugs. Reversible binding albumin was for systemic protraction optimal fatty acid linker combinations identified maximize while maintaining (GLP-1R) potency. GLP-1RAs mediate via this receptor, which is expressed pancreas, gastrointestinal tract, heart, lungs, kidneys brain. GLP-1Rs pancreas brain have been shown account respective improvements that are evident Both semaglutide also positively affect cardiovascular (CV) outcomes individuals T2D, although precise mechanism still being explored. Significant loss, through effect reduce energy intake, approval (3.0 mg) treatment obesity, indication currently under investigation Other include nonalcoholic liver disease (NASH) use oral formulation T2D. In summary, rational design has two analogs, made a vast contribution management T2D terms control, weight, blood pressure, lipids, beta-cell function CV outcomes. Furthermore, may provide additional benefits relation adherence. addition obesity NASH.

Language: Английский

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The Cardiovascular Biology of Glucagon-like Peptide-1

Cell Metabolism, Journal Year: 2016, Volume and Issue: 24(1), P. 15 - 30

Published: June 25, 2016

Language: Английский

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Cardiovascular Actions and Clinical Outcomes With Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors

Circulation, Journal Year: 2017, Volume and Issue: 136(9), P. 849 - 870

Published: Aug. 28, 2017

Potentiation of glucagon-like peptide-1 (GLP-1) action through selective GLP-1 receptor (GLP-1R) agonism or by prevention enzymatic degradation inhibition dipeptidyl peptidase-4 (DPP-4) promotes glycemic reduction for the treatment type 2 diabetes mellitus glucose-dependent control insulin and glucagon secretion. GLP-1R agonists also decelerate gastric emptying, reduce body weight food intake lower circulating lipoproteins, inflammation, systolic blood pressure. Preclinical studies demonstrate that both DPP-4 inhibitors exhibit cardioprotective actions in animal models myocardial ischemia ventricular dysfunction incompletely characterized mechanisms. The results cardiovascular outcome trials human subjects with increased risk have demonstrated a benefit (significant time to first major adverse event) liraglutide (LEADER trial [Liraglutide Effect Action Diabetes: Evaluation Cardiovascular Ourcome Results], −13%) semaglutide (SUSTAIN-6 [Trial Evaluate Other Long-term Outcomes Semaglutide], −24%). In contrast, examining safety shorter-acting agonist lixisenatide (ELIXA [Evaluation Lixisenatide Acute Coronary Syndrom]) saxagliptin (SAVOR-TIMI 53 [Saxagliptin Assessment Vascular Recorded Patients With Diabetes Mellitus-Thrombolysis Myocardial Infarction 53]), alogliptin (EXAMINE [Examination Alogliptin Versus Standard Care Type Mellitus Syndrome]), sitagliptin (TECOS Evaluating Sitagliptin]) found these agents neither nor decreased events. Here we review inhibitors, focus on translation mechanisms derived from preclinical complementary findings clinical studies. We highlight areas uncertainty requiring more careful scrutiny ongoing basic science As newer potent coagonists are being developed mellitus, obesity, nonalcoholic steatohepatitis, delineation potential underlie immediate relevance disease.

Language: Английский

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Effect of liraglutide, a glucagon‐like peptide‐1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)—a multicentre, double‐blind, randomised, placebo‐controlled trial

European Journal of Heart Failure, Journal Year: 2016, Volume and Issue: 19(1), P. 69 - 77

Published: Oct. 28, 2016

Language: Английский

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Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease

Physiological Reviews, Journal Year: 2015, Volume and Issue: 95(2), P. 513 - 548

Published: April 1, 2015

The preproglucagon gene ( Gcg) is expressed by specific enteroendocrine cells (L-cells) of the intestinal mucosa, pancreatic islet α-cells, and a discrete set neurons within nucleus solitary tract. Gcg encodes multiple peptides including glucagon, glucagon-like peptide-1, peptide-2, oxyntomodulin, glicentin. Of these, glucagon GLP-1 have received most attention because important roles in glucose metabolism, involvement diabetes other disorders, application to therapeutics. generally accepted model that improves homeostasis indirectly via stimulation nutrient-induced insulin release reducing secretion. Yet body literature surrounding physiology reveals an incompletely understood complex system includes peripheral central actions regulate energy homeostasis. On hand, established principally as counterregulatory hormone, increasing response physiological challenges threaten adequate blood levels driving production restore euglycemia. However, there also exists potential role for regulating expenditure has recently been suggested pharmacological studies. It becoming apparent cross-talk between proglucagon derived-peptides, e.g., inhibits secretion, some additive or synergistic interaction dual glucagon/GLP-1 agonists cause more weight loss than single agonists. In this review, we discuss functions both comparing contrasting how these function, variably concert opposition,

Language: Английский

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From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options

JHEP Reports, Journal Year: 2019, Volume and Issue: 1(4), P. 312 - 328

Published: July 19, 2019

The worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to have reached 25% or more in adults. NAFLD prevalent obese individuals, but may also affect non-obese insulin-resistant individuals. associated with a 2- 3-fold increased risk developing type 2 diabetes (T2D), which be higher patients severe – fibrosis increases this risk. In NAFLD, not only the close association obesity, impairment many metabolic pathways, including decreased hepatic insulin sensitivity and secretion, increase T2D related comorbidities. Conversely, steatohepatitis, end-stage disease. Genetics mechanisms involving dysfunctional adipose tissue, lipotoxicity glucotoxicity appear play role. review, we discuss altered pathophysiological that underlie development vice versa. Although there no approved therapy for treatment NASH, pharmacological agents currently available treat could potentially useful management NASH.

Language: Английский

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