A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity

Kelly, Aaron S.; Auerbach, Pernille; Barrientos-Pérez, Margarita; Gies, Inge; Hale, Paula M; Marcus, Claude; Mastrandrea, Lucy D.; Prabhu, Nandana; Arslanian, Silva; Investigators, Nn Trial

doi:10.1056/nejmoa1916038

Cited by 422 publications

(437 citation statements)

References 33 publications

Supporting

Mentioning

375

Contrasting

Unclassified

Order By: Relevance

“…The beneficial effects may be secondary to weight loss rather than direct effects on insulin sensitivity and cellular metabolic pathways. This is consistent with the results of a study of liraglutide in obese adolescents in which weight loss was achieved without significant change in other MetS parameters, such as insulin sensitivity and lipid levels [ 179 ]. The GLP-1 receptor agonists are safe but associated with significant symptoms of nausea and vomiting in some subjects [ 176 ].…”

Section: Approaches To Prevent or Reverse The Progression From Mhosupporting

confidence: 91%

Exploring Therapeutic Targets to Reverse or Prevent the Transition from Metabolically Healthy to Unhealthy Obesity

Dagpo

Nolan

Delghingaro-Augusto

2020

Cells

View full text Add to dashboard Cite

The prevalence of obesity and obesity-related metabolic comorbidities are rapidly increasing worldwide, placing a huge economic burden on health systems. Excessive nutrient supply combined with reduced physical exercise results in positive energy balance that promotes adipose tissue expansion. However, the metabolic response and pattern of fat accumulation is variable, depending on the individual’s genetic and acquired susceptibility factors. Some develop metabolically healthy obesity (MHO) and are resistant to obesity-associated metabolic diseases for some time, whereas others readily develop metabolically unhealthy obesity (MUO). An unhealthy response to excess fat accumulation could be due to susceptibility intrinsic factors (e.g., increased likelihood of dedifferentiation and/or inflammation), or by pathogenic drivers extrinsic to the adipose tissue (e.g., hyperinsulinemia), or a combination of both. This review outlines the major transcriptional factors and genes associated with adipogenesis and regulation of adipose tissue homeostasis and describes which of these are disrupted in MUO compared to MHO individuals. It also examines the potential role of pathogenic insulin hypersecretion as an extrinsic factor capable of driving the changes in adipose tissue which cause transition from MHO to MUO. On this basis, therapeutic approaches currently available and emerging to prevent and reverse the transition from MHO to MUO transition are reviewed.

show abstract

Section: Approaches To Prevent or Reverse The Progression From Mhosupporting

confidence: 91%

Exploring Therapeutic Targets to Reverse or Prevent the Transition from Metabolically Healthy to Unhealthy Obesity

Dagpo

Nolan

Delghingaro-Augusto

2020

Cells

View full text Add to dashboard Cite

show abstract

“…Levels of TG, apo B, and non-HDL-C rose from baseline to the end of the first year and remained at a higher level for the next 2 years. Only improved glycemic control and weight loss have been associated with improvement in lipid levels Liraglutide [86,87] ↓ ↔ ↔ No differences were apparent in longer term studies. Unclear if the results due mostly normal lipids at baseline/limited sample size Bariatric surgery [88][89][90][91][92] ↓ ↑ Mild ↓ Minor complications were higher in adolescent studies.…”

Section: Ongoing Clinical Studies For Dyslipidemia In T2dmentioning

confidence: 99%

Dyslipidemia in Pediatric Type 2 Diabetes Mellitus

Sunil

Ashraf

2020

Curr Diab Rep

View full text Add to dashboard Cite

Purpose of Review Cardiovascular (CV) disease is a major cause of mortality in type 2 diabetes mellitus (T2D). Dyslipidemia is prevalent in children with T2D and is a known risk factor for CVD. In this review, we critically examine the epidemiology, pathophysiology, and recommendations for dyslipidemia management in pediatric T2D. Recent Findings Dyslipidemia is multifactorial and related to poor glycemic control, insulin resistance, inflammation, and genetic susceptibility. Current guidelines recommend lipid screening after achieving glycemic control and annually thereafter. The desired lipid goals are low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL, high-density lipoprotein cholesterol (HDL-C) > 35 mg/dL, and triglycerides (TG) < 150 mg/dL. Summary If LDL-C remains > 130 mg/dL after 6 months, statins are recommended with a treatment goal of < 100 mg/dL. If fasting TG are > 400 mg/dL or non-fasting TG are > 1000 mg/dL, fibrates are recommended. Although abnormal levels of atherogenic TG-rich lipoproteins, apolipoprotein B, and non-HDL-C are commonly present in pediatric T2D, their measurement is not currently considered in risk assessment or management.

show abstract

“…Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut-derived incretin hormones, known to stimulate insulin secretion for glycemic control, and in the case of GLP-1, also recognized to promote satiety, which has led to the development of a GLP-1 receptor (GLP-1R) agonist (GLP-1RA) as an obesity therapy 1 . More recently, therapies targeting the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) have shown efficacy preclinically in preventing weight gain 2 – 5 .…”

Section: Introductionmentioning

confidence: 99%

Chronic glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism desensitizes adipocyte GIPR activity mimicking functional GIPR antagonism

et al. 2020

View full text Add to dashboard Cite

Antagonism or agonism of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) prevents weight gain and leads to dramatic weight loss in combination with glucagon-like peptide-1 receptor agonists in preclinical models. Based on the genetic evidence supporting GIPR antagonism, we previously developed a mouse anti-murine GIPR antibody (muGIPR-Ab) that protected diet-induced obese (DIO) mice against body weight gain and improved multiple metabolic parameters. This work reconciles the similar preclinical body weight effects of GIPR antagonists and agonists in vivo, and here we show that chronic GIPR agonism desensitizes GIPR activity in primary adipocytes, both differentiated in vitro and adipose tissue in vivo, and functions like a GIPR antagonist. Additionally, GIPR activity in adipocytes is partially responsible for muGIPR-Ab to prevent weight gain in DIO mice, demonstrating a role of adipocyte GIPR in the regulation of adiposity in vivo.

show abstract

A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity

Cited by 422 publications

References 33 publications

Exploring Therapeutic Targets to Reverse or Prevent the Transition from Metabolically Healthy to Unhealthy Obesity

Exploring Therapeutic Targets to Reverse or Prevent the Transition from Metabolically Healthy to Unhealthy Obesity

Dyslipidemia in Pediatric Type 2 Diabetes Mellitus

Chronic glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism desensitizes adipocyte GIPR activity mimicking functional GIPR antagonism

Contact Info

Product

Resources

About