Discovery, characterization, and clinical development of the glucagon-like peptides

Drucker, Daniel J.; Habener, Joel F.; Holst, Jens J.

doi:10.1172/jci97233

Cited by 295 publications

(250 citation statements)

References 106 publications

Supporting

Mentioning

238

Contrasting

Unclassified

Order By: Relevance

“…Liraglutide (gift of NovoNordisk, Bagsværd, Denmark) was dissolved in 0.1 M phosphate‐buffered saline (pH 7.4) for systemic injections. Liraglutide is a selective GLP‐1R agonist in humans and rodents …”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Liraglutide pharmacotherapy reduces body weight and improves glycaemic control in juvenile obese/hyperglycaemic male and female rats

Liberini

Lhamo

Ghidewon

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

Aims: To examine whether the glucagon-like peptide-1 receptor agonist liraglutide could be used in juvenile male and female rats as an anti-obesity/diabetic pharmaceutical to prevent not only adolescent obesity/hyperglycaemia, but also early-adult onset obesity. Material and Methods: Pregnant dams were fed either standard chow or a high-fat, highsucrose diet (HFSD) from gestational day 2, throughout pregnancy and lactation. Offspring were weaned onto the respective maternal diet. Juveniles received daily subcutaneous injection of liraglutide (50 μg/kg, from postnatal day [PND]30 to PND40 and 200 μg/kg from PND40 to PND60) or vehicle. Food intake, body weight and glycaemic levels were evaluated across the experimental period.Results: Chronic liraglutide administration in juveniles prevented body weight gain in males and retained a normoglycaemic profile in both male and female rats.Conclusion: These preclinical data suggest that maternal and early-life consumption of an HFSD increases caloric intake, body weight gain and hyperglycaemia, a collective set of unwanted metabolic effects that appear to be treatable in juveniles with liraglutide pharmacotherapy intervention. K E Y W O R D Sanimal pharmacology, GLP-1 analogue, liraglutide, neuropharmacology

show abstract

Section: Methodsmentioning

confidence: 99%

“…Liraglutide is a selective GLP-1R agonist in humans and rodents. 9,[24][25][26][27] 2.3 | Effects of chronic daily administration of liraglutide in juvenile male and female rats on body weight gain and food intake…”

Section: Drugsmentioning

confidence: 99%

Liraglutide pharmacotherapy reduces body weight and improves glycaemic control in juvenile obese/hyperglycaemic male and female rats

Liberini

Lhamo

Ghidewon

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…It seems timely to ask whether the agency-mandated warnings surrounding pancreatitis and MTC for GLP-1R agonists do more harm than good, given the associated apprehension versus the actual clinical data from CVOTs and the potential for reduction of MACE and cardiovascular death. The therapeutic benefit of the GLP-1 system for diabetes and obesity is now firmly established, based on a combination of robust basic and clinical science (1,33). Although we still have much to learn, the road ahead is well paved, brightly illuminated, and holds much promise for ongoing innovation in the treatment of metabolic disease.…”

Section: Areas Of Uncertaintymentioning

confidence: 99%

“…Much of our original understanding of glucagon-like peptide 1 (GLP-1) biology stems from studies in obese animals and humans, with and without diabetes, examining the actions of native GLP-1 (1). Notably, the actions of GLP-1 are highly conserved from small animals to primates, enabling the pivotal demonstration that continuous GLP-1 administration for 6 weeks reduced glucose and body weight while improving insulin sensitivity in human subjects with type 2 diabetes (T2D) (2).…”

mentioning

confidence: 99%

“…Notably, the actions of GLP-1 are highly conserved from small animals to primates, enabling the pivotal demonstration that continuous GLP-1 administration for 6 weeks reduced glucose and body weight while improving insulin sensitivity in human subjects with type 2 diabetes (T2D) (2). The finding that native GLP-1 was rapidly cleared by the kidney and highly sensitive to enzymatic inactivation by dipeptidyl peptidase 4 (DPP-4) shifted the focus for clinical development away from native GLP-1 and toward longer-acting degradation-resistant GLP-1 receptor (GLP-1R) agonists (1). The recent findings that some, but not all, GLP-1R agonists reduce the rates of cardiovascular events in humans with T2D has heightened the interest in mechanisms linking GLP-1R activation to cardioprotection.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Ascending GLP-1 Road From Clinical Safety to Reduction of Cardiovascular Complications

Drucker

2018

Diabetes

Self Cite

View full text Add to dashboard Cite

Glucagon-like peptide 1 (GLP-1) was originally identified as a gut-derived incretin hormone that lowered glycemia through potentiation of glucose-dependent insulin secretion. Subsequent studies expanded the actions of GLP-1 to include inhibition of glucagon secretion, gastric emptying, and appetite, collectively useful attributes for a glucose-lowering agent. The introduction of GLP-1 receptor (GLP-1R) agonists for the treatment of diabetes was associated with questions surrounding their safety, principally with regard to medullary thyroid cancer, pancreatitis, and pancreatic cancer, yet cardiovascular outcome trials subsequently revealed reductions in rates of stroke, myocardial infarction, and cardiovascular death with a paucity of major safety signals. We discuss the controversies, unanswered questions, and established use of GLP-1R agonists from a mechanistic and clinical perspective. We highlight methods for detection and cellular sites of GLP-1R expression, key uncertainties, recent insights, and experimental caveats surrounding the use of GLP-1R agonists for the treatment of diabetes and the reduction of diabetes-related complications.

show abstract

Evaluation of the Cascade of Diabetes Care in the United States, 2005-2016

et al. 2019

View full text Add to dashboard Cite

IMPORTANCE Treatment advances in diabetes can meaningfully improve outcomes only if they effectively reach the populations at risk. OBJECTIVES To evaluate whether the cascade of US diabetes care, defined as diabetes diagnosis, linkage to care, and achievement of individual and combined treatment targets, improved from 2005 to 2016 and to investigate potential disparities in US diabetes care. DESIGN, SETTING, AND PARTICIPANTS Nationally representative, serial cross-sectional studies included in the 2005-2016 National Health and Nutrition Examination Survey were evaluated. Data on nonpregnant US adults (age Ն18 years) with diabetes who had reported fasting for 9 or more hours (n = 1742 diagnosed and 746 undiagnosed) were included. Data analysis was performed from August 1, 2018, to May 10, 2019.

show abstract

Discovery, characterization, and clinical development of the glucagon-like peptides

Cited by 295 publications

References 106 publications

Liraglutide pharmacotherapy reduces body weight and improves glycaemic control in juvenile obese/hyperglycaemic male and female rats

Liraglutide pharmacotherapy reduces body weight and improves glycaemic control in juvenile obese/hyperglycaemic male and female rats

The Ascending GLP-1 Road From Clinical Safety to Reduction of Cardiovascular Complications

Evaluation of the Cascade of Diabetes Care in the United States, 2005-2016

Contact Info

Product

Resources

About