CNS-targeting pharmacological interventions for the metabolic syndrome

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans

(2019) Satish Patel et al.   Cell Metabolism

Melanocortin-4 Receptor Signalling: Importance for Weight Regulation and Obesity Treatment

(2019) Peter Kühnen et al.   TRENDS IN MOLECULAR MEDICINE

Activation of Agrp neurons modulates memory-related cognitive processes in mice

(2019) Marcelo R. Zimmer et al.   PHARMACOLOGICAL RESEARCH

IL1R1 is required for celastrol’s leptin-sensitization and antiobesity effects

(2019) Xudong Feng et al.   NATURE MEDICINE

The Hypothalamic Arcuate Nucleus-Median Eminence is a Target for Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1

(2019) Jenny M. Brown et al.   DIABETES

A GLP-1:CCK fusion peptide harnesses the synergistic effects on metabolism of CCK-1 and GLP-1 receptor agonism in mice

(2018) David C. Hornigold et al.   APPETITE

Obesity

(2018) Kishore M. Gadde et al.   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study

(2018) Philip Ambery et al.   LANCET

MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency

(2018) Karine Clément et al.   NATURE MEDICINE

Gut hormone polyagonists for the treatment of type 2 diabetes

(2018) Sara J. Brandt et al.   PEPTIDES

How and why do gastrointestinal peptides influence food intake?

(2018) Stephen C. Woods et al.   PHYSIOLOGY & BEHAVIOR

Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial

(2018) Richard E Pratley et al.   Lancet Diabetes & Endocrinology

Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis

(2018) M Angelyn Bethel et al.   Lancet Diabetes & Endocrinology

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

(2018) Daniel J. Drucker   DIABETES

Celastrol Induced Weight Loss is Driven by Hypophagia and Independent From UCP1

(2018) Katrin Pfuhlmann et al.   DIABETES

A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo-controlled first-in-human and first-in-patient trials

(2018) Joachim Tillner et al.   DIABETES OBESITY & METABOLISM

Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial

(2018) Patrick M O'Neil et al.   LANCET

Genetic identification of leptin neural circuits in energy and glucose homeostases

(2018) Jie Xu et al.   NATURE

Fluorescent blood–brain barrier tracing shows intact leptin transport in obese mice

(2018) Luke Harrison et al.   INTERNATIONAL JOURNAL OF OBESITY

Celastrol Promotes Weight Loss in Diet-Induced Obesity by Inhibiting the Protein Tyrosine Phosphatases PTP1B and TCPTP in the Hypothalamus

(2018) Eleni Kyriakou et al.   JOURNAL OF MEDICINAL CHEMISTRY

Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial

(2018) Juan Pablo Frias et al.   LANCET

Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61): a randomised, placebo-controlled trial

(2018) Erin A Bohula et al.   LANCET

Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism

(2018) Cristina García-Cáceres et al.   NATURE NEUROSCIENCE

Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models

(2018) Elizabeth A. Killion et al.   Science Translational Medicine

Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism

(2018) Piotr A. Mroz et al.   Molecular Metabolism

Targeted delivery of antisense oligonucleotides to pancreatic β-cells

(2018) C. Ämmälä et al.   Science Advances

Blaming the Brain for Obesity: Integration of Hedonic and Homeostatic Mechanisms

(2017) Hans-Rudolf Berthoud et al.   GASTROENTEROLOGY

Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes

(2017) Melanie Davies et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

A potent, selective, and orally bioavailable inhibitor of the protein-tyrosine phosphatase PTP1B improves insulin and leptin signaling in animal models

(2017) Navasona Krishnan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand

(2017) Linda Yang et al.   NATURE MEDICINE

GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates

(2017) Shannon E Mullican et al.   NATURE MEDICINE

The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL

(2017) Paul J Emmerson et al.   NATURE MEDICINE

Evolution of physicochemical properties of melanin concentrating hormone receptor 1 (MCHr1) antagonists

(2016) Anders Johansson   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Effects of Moderate and Subsequent Progressive Weight Loss on Metabolic Function and Adipose Tissue Biology in Humans with Obesity

(2016) Faidon Magkos et al.   Cell Metabolism

A meta-analysis comparing clinical effects of short- or long-acting GLP-1 receptor agonists versus insulin treatment from head-to-head studies in type 2 diabetic patients

(2016) Mirna S. Abd El Aziz et al.   DIABETES OBESITY & METABOLISM

Renaissance of leptin for obesity therapy

(2016) Carmelo Quarta et al.   DIABETOLOGIA

Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents

(2016) Jarrad M Scarlett et al.   NATURE MEDICINE

Withaferin A is a leptin sensitizer with strong antidiabetic properties in mice

(2016) Jaemin Lee et al.   NATURE MEDICINE

Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist

(2016) Peter Kühnen et al.   NEW ENGLAND JOURNAL OF MEDICINE

Treatment of Obesity with Celastrol

(2015) Junli Liu et al.   CELL

Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding

(2015) Marcelo O. Dietrich et al.   CELL

Diet-Induced Obese Mice Retain Endogenous Leptin Action

(2015) Nickki Ottaway et al.   Cell Metabolism

Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding

(2015) Michael J. Waterson et al.   Cell Metabolism

Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide

(2015) Jesper Lau et al.   JOURNAL OF MEDICINAL CHEMISTRY

Antagonism of gastric inhibitory polypeptide (GIP) by palmitoylation of GIP analogues with N- and C-terminal modifications improves obesity and metabolic control in high fat fed mice

(2015) V. Pathak et al.   MOLECULAR AND CELLULAR ENDOCRINOLOGY

The anti-diabetic effects of GLP-1-gastrin dual agonist ZP3022 in ZDF rats

(2015) Jolanta Skarbaliene et al.   PEPTIDES

AgRP Neurons Regulate Bone Mass

(2015) Jae Geun Kim et al.   Cell Reports

Meteorin-like Is a Hormone that Regulates Immune-Adipose Interactions to Increase Beige Fat Thermogenesis

(2014) Rajesh R. Rao et al.   CELL

O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat

(2014) Hai-Bin Ruan et al.   CELL

Adipsin Is an Adipokine that Improves β Cell Function in Diabetes

(2014) James C. Lo et al.   CELL

GLP-1–oestrogen attenuates hyperphagia and protects from beta cell failure in diabetes-prone New Zealand obese (NZO) mice

(2014) Robert W. Schwenk et al.   DIABETOLOGIA

The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss

(2014) Anna Secher et al.   JOURNAL OF CLINICAL INVESTIGATION

Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial

(2014) Kathleen M Dungan et al.   LANCET

A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents

(2014) Brian Finan et al.   NATURE MEDICINE

Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study

(2014) Richard E Pratley et al.   Lancet Diabetes & Endocrinology

GLP-1 receptor agonists: a review of head-to-head clinical studies

(2014) Jennifer M. Trujillo et al.   Therapeutic Advances in Endocrinology and Metabolism

The insulin sensitizing effect of topiramate involves KATPchannel activation in the central nervous system

(2013) C P Coomans et al.   BRITISH JOURNAL OF PHARMACOLOGY

GLP-1/Glucagon Coagonism Restores Leptin Responsiveness in Obese Mice Chronically Maintained on an Obesogenic Diet

(2013) C. Clemmensen et al.   DIABETES

Efficacy and Safety of Lixisenatide Once Daily Versus Exenatide Twice Daily in Type 2 Diabetes Inadequately Controlled on Metformin: A 24-week, randomized, open-label, active-controlled study (GetGoal-X)

(2013) J. Rosenstock et al.   DIABETES CARE

Effects of Naltrexone Sustained- Release/Bupropion Sustained-Release Combination Therapy on Body Weight and Glycemic Parameters in Overweight and Obese Patients With Type 2 Diabetes

(2013) P. Hollander et al.   DIABETES CARE

A novel long-acting glucose-dependent insulinotropic peptide analogue: enhanced efficacy in normal and diabetic rodents

(2013) K. Tatarkiewicz et al.   DIABETES OBESITY & METABOLISM

Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

(2013) Eric D. Berglund et al.   JOURNAL OF CLINICAL INVESTIGATION

Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults

(2013) Louis J. Aronne et al.   Obesity

Eight-year weight losses with an intensive lifestyle intervention: The look AHEAD study

(2013)   Obesity

Improved Glucose Control and Reduced Body Weight in Rodents with Dual Mechanism of Action Peptide Hybrids

(2013) James L. Trevaskis et al.   PLoS One

Effects of lixisenatide once daily on gastric emptying in type 2 diabetes — Relationship to postprandial glycemia

(2013) Martin Lorenz et al.   REGULATORY PEPTIDES

Unimolecular Dual Incretins Maximize Metabolic Benefits in Rodents, Monkeys, and Humans

(2013) B. Finan et al.   Science Translational Medicine

Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21

(2012) Timo D. Müller et al.   JOURNAL OF PEPTIDE SCIENCE

Neutral antagonism at the cannabinoid 1 receptor: a safer treatment for obesity

(2012) F J Meye et al.   MOLECULAR PSYCHIATRY

A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis

(2012) Pontus Boström et al.   NATURE

Targeted estrogen delivery reverses the metabolic syndrome

(2012) Brian Finan et al.   NATURE MEDICINE

AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors

(2012) Marcelo O Dietrich et al.   NATURE NEUROSCIENCE

The Opioid System and Food Intake: Homeostatic and Hedonic Mechanisms

(2012) Ruben Nogueiras et al.   Obesity Facts

Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study

(2011) W Timothy Garvey et al.   AMERICAN JOURNAL OF CLINICAL NUTRITION

NPY receptors as potential targets for anti-obesity drug development

(2011) Ernie Yulyaningsih et al.   BRITISH JOURNAL OF PHARMACOLOGY

Intracellular Signals Mediating the Food Intake-Suppressive Effects of Hindbrain Glucagon-like Peptide-1 Receptor Activation

(2011) Matthew R. Hayes et al.   Cell Metabolism

Rapid Tachyphylaxis of the Glucagon-Like Peptide 1-Induced Deceleration of Gastric Emptying in Humans

(2011) M. A. Nauck et al.   DIABETES

A 5-week study of the pharmacokinetics and pharmacodynamics of LY2189265, a novel, long-acting glucagon-like peptide-1 analogue, in patients with type 2 diabetes

(2011) P. Barrington et al.   DIABETES OBESITY & METABOLISM

Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial

(2011) Kishore M Gadde et al.   LANCET

Controlled-Release Phentermine/Topiramate in Severely Obese Adults: A Randomized Controlled Trial (EQUIP)

(2011) David B. Allison et al.   Obesity

Pharmacokinetics and Pharmacodynamics of Exenatide Extended-Release After Single and Multiple Dosing

(2010) Mark Fineman et al.   CLINICAL PHARMACOKINETICS

Central and Peripheral Molecular Targets for Antiobesity Pharmacotherapy

(2010) M A Valentino et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Lorcaserin, A 5-HT2CReceptor Agonist, Reduces Body Weight by Decreasing Energy Intake without Influencing Energy Expenditure

(2010) Corby K. Martin et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

(2010) Frank L Greenway et al.   LANCET

The metabolic actions of glucagon revisited

(2010) Kirk M. Habegger et al.   Nature Reviews Endocrinology

Multicenter, Placebo-Controlled Trial of Lorcaserin for Weight Management

(2010) Steven R. Smith et al.   NEW ENGLAND JOURNAL OF MEDICINE

Effect of Sibutramine on Cardiovascular Outcomes in Overweight and Obese Subjects

(2010) W. Philip T. James et al.   NEW ENGLAND JOURNAL OF MEDICINE

Inhibition of PTP1B by Trodusquemine (MSI-1436) Causes Fat-specific Weight Loss in Diet-induced Obese Mice

(2010) Kristen A. Lantz et al.   Obesity

The novel cannabinoid CB1 antagonist AM6545 suppresses food intake and food-reinforced behavior

(2010) P.A. Randall et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Brain serotonin system in the coordination of food intake and body weight

(2010) Daniel D. Lam et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Harmonizing the Metabolic Syndrome

(2009) K.G.M.M. Alberti et al.   CIRCULATION

Potent and Selective Agonism of the Melanocortin Receptor 4 With MK-0493 Does Not Induce Weight Loss in Obese Human Subjects: Energy Intake Predicts Lack of Weight Loss Efficacy

(2009) R Krishna et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Glucagon-Like Peptide 1/Glucagon Receptor Dual Agonism Reverses Obesity in Mice

(2009) A. Pocai et al.   DIABETES

Safety, tolerability, pharmacodynamics and pharmacokinetics of albiglutide, a long-acting glucagon-like peptide-1 mimetic, in healthy subjects

(2009) M. A. Bush et al.   DIABETES OBESITY & METABOLISM

Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)

(2009) John B Buse et al.   LANCET

Metabolic Syndrome and Cancer

(2009) Pooja Pothiwala et al.   Metabolic Syndrome and Related Disorders

A new glucagon and GLP-1 co-agonist eliminates obesity in rodents

(2009) Jonathan W Day et al.   Nature Chemical Biology

‘Liking’ and ‘wanting’ food rewards: Brain substrates and roles in eating disorders

(2009) Kent C. Berridge   PHYSIOLOGY & BEHAVIOR

America’s First Amphetamine Epidemic 1929–1971

(2008) Nicolas Rasmussen   AMERICAN JOURNAL OF PUBLIC HEALTH

Ghrelin Modulates Brain Activity in Areas that Control Appetitive Behavior

(2008) Saima Malik et al.   Cell Metabolism

Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas

(2008) J. de Heer et al.   DIABETOLOGIA

Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial

(2008) Arne Astrup et al.   LANCET

Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study

(2008) Daniel J Drucker et al.   LANCET

5-HT2CRs Expressed by Pro-Opiomelanocortin Neurons Regulate Energy Homeostasis

(2008) Yong Xu et al.   NEURON

Modulation of Blood Pressure by Central Melanocortinergic Pathways

(2008) Jerry R. Greenfield et al.   NEW ENGLAND JOURNAL OF MEDICINE

Leptin responsiveness restored by amylin agonism in diet-induced obesity: Evidence from nonclinical and clinical studies

(2008) J. D. Roth et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Effect of exenatide on gastric emptying and relationship to postprandial glycemia in type 2 diabetes

(2008) Helle Linnebjerg et al.   REGULATORY PEPTIDES

Mutations in ligands and receptors of the leptin–melanocortin pathway that lead to obesity

(2008) I Sadaf Farooqi et al.   Nature clinical practice. Endocrinology & metabolism

Supraphysiological doses of intravenous PYY3-36 cause nausea, but no additional reduction in food intake

(2008) Carel W le Roux et al.   ANNALS OF CLINICAL BIOCHEMISTRY

Serotonin 5-HT2CReceptor Agonist Promotes Hypophagia via Downstream Activation of Melanocortin 4 Receptors

(2007) Daniel D. Lam et al.   ENDOCRINOLOGY