Recent Advances in Incretin-Based Pharmacotherapies for the Treatment of Obesity and Diabetes

The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling

(2021) Qian Zhang et al.   Cell Metabolism

Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity

(2021) Thomas A. Wadden et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial

(2021) Melanie Davies et al.   LANCET

Once-Weekly Semaglutide in Adults with Overweight or Obesity

(2021) John P.H. Wilding et al.   NEW ENGLAND JOURNAL OF MEDICINE

Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity

(2021) Domenica Rubino et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing

(2021) Georgina K.C. Dowsett et al.   Molecular Metabolism

GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs

(2021) Dario Giugliano et al.   Cardiovascular Diabetology

80-LB: Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, Is Effective and Safe When Added to Basal Insulin for Treatment of Type 2 Diabetes (SURPASS-5)

(2021) DOMINIK DAHL et al.   DIABETES

GIP Receptor Agonism Attenuates GLP-1 Receptor Agonist Induced Nausea and Emesis in Preclinical Models

(2021) Tito Borner et al.   DIABETES

Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial

(2021) Julio Rosenstock et al.   LANCET

Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial

(2021) Bernhard Ludvik et al.   LANCET

Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes

(2021) Juan P. Frías et al.   NEW ENGLAND JOURNAL OF MEDICINE

Spatiotemporal GLP-1 and GIP receptor signaling and trafficking/recycling dynamics induced by selected receptor mono- and dual-agonists

(2021) Aaron Novikoff et al.   Molecular Metabolism

Wegovy (semaglutide): a new weight loss drug for chronic weight management

(2021) Gurdeep Singh et al.   JOURNAL OF INVESTIGATIVE MEDICINE

Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial

(2021) Stefano Del Prato et al.   LANCET

Anti-obesity drug discovery: advances and challenges

(2021) Timo D. Müller et al.   NATURE REVIEWS DRUG DISCOVERY

Efficacy and tolerability of tirzepatide, a dual glucose‐dependent insulinotropic peptide and glucagon‐like peptide‐1 receptor agonist in patients with type 2 diabetes: A 12‐week, randomized, double‐blind, placebo‐controlled study to evaluate different dose‐escalation regimens

(2020) Juan Pablo Frias et al.   DIABETES OBESITY & METABOLISM

GIP as a therapeutic target in diabetes and obesity: insight from incretin co-agonists

(2020) Jens Juul Holst et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Young-onset type 2 diabetes mellitus — implications for morbidity and mortality

(2020) Dianna J. Magliano et al.   Nature Reviews Endocrinology

How May GIP Enhance the Therapeutic Efficacy of GLP-1?

(2020) Ricardo J. Samms et al.   TRENDS IN ENDOCRINOLOGY AND METABOLISM

Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist

(2020) Francis S. Willard et al.   JCI Insight

Targeting the GIPR for obesity: To agonize or antagonize? Potential mechanisms

(2020) Jonathan E. Campbell   Molecular Metabolism

The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials

(2020) Thinzar Min et al.   Diabetes Therapy

Lack of Treatment Persistence and Treatment Nonadherence as Barriers to Glycaemic Control in Patients with Type 2 Diabetes

(2019) Bruno Guerci et al.   Diabetes Therapy

Sacubitril/valsartan augments postprandial plasma concentrations of active GLP-1 when combined with sitagliptin in men

(2019) Nicolai J Wewer Albrechtsen et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

The Discovery and Development of Liraglutide and Semaglutide

(2019) Lotte Bjerre Knudsen et al.   Frontiers in Endocrinology

Glucose-Dependent Insulinotropic Polypeptide Receptor-Expressing Cells in the Hypothalamus Regulate Food Intake

(2019) Alice E. Adriaenssens et al.   Cell Metabolism

Gut-derived GIP activates central Rap1 to impair neural leptin sensitivity during overnutrition

(2019) Kentaro Kaneko et al.   JOURNAL OF CLINICAL INVESTIGATION

Glucagon-like peptide 1 (GLP-1)

(2019) T.D. Müller et al.   Molecular Metabolism

Increased Body Weight and Fat Mass After Subchronic GIP Receptor Antagonist, but Not GLP-2 Receptor Antagonist, Administration in Rats

(2019) Sara Baldassano et al.   Frontiers in Endocrinology

The glucose-dependent insulinotropic polypeptide signaling axis in the central nervous system

(2019) A.E. Adriaenssens et al.   PEPTIDES

GIP has neuroprotective effects in Alzheimer and Parkinson’s disease models

(2019) Zhen Qiang Zhang et al.   PEPTIDES

GIP and the gut-bone axis – Physiological, pathophysiological and potential therapeutic implications

(2019) Signe Stensen et al.   PEPTIDES

Physiological roles of the GIP receptor in murine brown adipose tissue

(2019) Jacqueline L. Beaudry et al.   Molecular Metabolism

Mono-PEGylates of exenatide in branched and dimeric structures can improve in vivo stability and hypoglycemic bioactivity

(2019) Ngoc-Thanh Thi Nguyen et al.   JOURNAL OF BIOTECHNOLOGY

Recent advances of GIP and future horizons

(2019) Jens Juul Holst et al.   PEPTIDES

Pharmacological antagonism of the incretin system protects against diet-induced obesity

(2019) Berit Svendsen et al.   Molecular Metabolism

MEDI0382, a GLP-1-glucagon receptor dual agonist, meets safety and tolerability endpoints in a single-dose, healthy-subject, randomised, phase 1 study

(2018) Philip D. Ambery et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Xenopus -derived glucagon-like peptide-1 and polyethylene-glycosylated glucagon-like peptide-1 receptor agonists: long-acting hypoglycaemic and insulinotropic activities with potential therapeutic utilities

(2018) Jing Han et al.   BRITISH JOURNAL OF PHARMACOLOGY

OWL833, an Orally Active Nonpeptide GLP-1 Receptor Agonist, Improves Glucose Tolerance by Increasing Insulin Secretion and Reduces Food Intake of Cynomolgus Monkeys

(2018) TAKAHIRO KAWAI et al.   DIABETES

Continuing rise of Type 2 diabetes incidence in children and young people in the UK

(2018) T. P. Candler et al.   DIABETIC MEDICINE

Liraglutide, a human glucagon-like peptide-1 analogue, stimulates AKT-dependent survival signalling and inhibits pancreatic β-cell apoptosis

(2018) Katerina Kapodistria et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

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

Type 2 diabetes in adolescents and young adults

(2018) Nadia Lascar et al.   Lancet Diabetes & Endocrinology

C-terminal site-specific PEGylated Exendin-4 analog: A long-acting glucagon like Peptide-1 receptor agonist, on glycemic control and beta cell function in diabetic db/db mice

(2018) Daoqi Tang et al.   JOURNAL OF PHARMACOLOGICAL SCIENCES

Anti-Obesity Therapy: from Rainbow Pills to Polyagonists

(2018) T. D. Müller et al.   PHARMACOLOGICAL REVIEWS

Protective effects of glucagon-like peptide-1 (GLP-1) analogue exenatide against glucose and fructose-induced neurotoxicity

(2018) Asghar Khalilnezhad et al.   INTERNATIONAL JOURNAL OF NEUROSCIENCE

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

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

Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist

(2018) Stephen T. Buckley 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

LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept

(2018) Tamer Coskun et al.   Molecular Metabolism

Health Effects of Overweight and Obesity in 195 Countries over 25 Years

(2017)   NEW ENGLAND JOURNAL OF MEDICINE

A systematic review of genetic syndromes with obesity

(2017) Y. Kaur et al.   Obesity Reviews

On the origin of obesity: identifying the biological, environmental and cultural drivers of genetic risk among human populations

(2017) A. Qasim et al.   Obesity Reviews

Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation

(2017) G.A. Bray et al.   Obesity Reviews

The New Biology and Pharmacology of Glucagon

(2017) T. D. Müller et al.   PHYSIOLOGICAL REVIEWS

Economic Burden of Obesity: A Systematic Literature Review

(2017) Maximilian Tremmel et al.   International Journal of Environmental Research and Public Health

Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review

(2016) Igho J. Onakpoya et al.   BMC Medicine

Unimolecular Polypharmacy for Treatment of Diabetes and Obesity

(2016) Matthias H. Tschöp et al.   Cell Metabolism

Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity

(2016) M. Pigeyre et al.   CLINICAL SCIENCE

Self-reported Barriers to Adherence and Persistence to Treatment With Injectable Medications for Type 2 Diabetes

(2016) C. Victor Spain et al.   CLINICAL THERAPEUTICS

PEGylation of Biopharmaceuticals: A Review of Chemistry and Nonclinical Safety Information of Approved Drugs

(2016) Peter L. Turecek et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

(2016) Steven P. Marso et al.   NEW ENGLAND JOURNAL OF MEDICINE

Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

(2016) Steven P. Marso et al.   NEW ENGLAND JOURNAL OF MEDICINE

Reappraisal of GIP Pharmacology for Metabolic Diseases

(2016) Brian Finan et al.   TRENDS IN MOLECULAR MEDICINE

Comprehensive alpha, beta and delta cell transcriptomes reveal that ghrelin selectively activates delta cells and promotes somatostatin release from pancreatic islets

(2016) Michael R. DiGruccio et al.   Molecular Metabolism

A healthy gastrointestinal microbiome is dependent on dietary diversity

(2016) Mark L. Heiman et al.   Molecular Metabolism

Health Benefits of Long-Term Weight-Loss Maintenance

(2015) Christian F. Rueda-Clausen et al.   Annual Review of Nutrition

Species-specific action of (Pro3)GIP - a full agonist at human GIP receptors, but a partial agonist and competitive antagonist at rat and mouse GIP receptors

(2015) A H Sparre-Ulrich et al.   BRITISH JOURNAL OF PHARMACOLOGY

Novel Pentapeptide GLP-1 (32-36) Amide Inhibitsβ-Cell ApoptosisIn Vitroand Improves Glucose Disposal in Streptozotocin-Induced Diabetic Mice

(2015) Lidan Sun et al.   Chemical Biology & Drug Design

Pancreatic glucose-dependent insulinotropic polypeptide (GIP) (1–30) expression is upregulated in diabetes and PEGylated GIP(1–30) can suppress the progression of low-dose-STZ-induced hyperglycaemia in mice

(2015) Tsuyoshi Yanagimachi et al.   DIABETOLOGIA

Long-acting hypoglycemic effects of PEGylated FGF21 and insulin glargine in mice with type 1 diabetes

(2015) Pengfei Xu et al.   JOURNAL OF DIABETES AND ITS COMPLICATIONS

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

(2015) Xavier Pi-Sunyer et al.   NEW ENGLAND JOURNAL OF MEDICINE

Adipose Tissue Dysfunction and Impaired Metabolic Health in Human Obesity: A Matter of Oxygen?

(2015) Gijs H. Goossens et al.   Frontiers in Endocrinology

Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans

(2014) Rune E. Kuhre et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Hindbrain nucleus tractus solitarius glucagon-like peptide-1 receptor signaling reduces appetitive and motivational aspects of feeding

(2014) Amber L. Alhadeff et al.   AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY

A solid-phase PEGylation strategy for protein therapeutics using a potent FGF21 analog

(2014) Lintao Song et al.   BIOMATERIALS

Cardiovascular Effects of Current and Future Anti-Obesity Drugs

(2014) Simon Comerma-Steffensen et al.   Current Vascular Pharmacology

The Human GLP-1 Analogs Liraglutide and Semaglutide: Absence of Histopathological Effects on the Pancreas in Nonhuman Primates

(2014) C. F. Gotfredsen et al.   DIABETES

GLP-1 Receptor Localization in Monkey and Human Tissue: Novel Distribution Revealed With Extensively Validated Monoclonal Antibody

(2014) Charles Pyke et al.   ENDOCRINOLOGY

Pharmacology, Physiology, and Mechanisms of Incretin Hormone Action

(2013) Jonathan E. Campbell et al.   Cell Metabolism

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

(2013) C. Clemmensen et al.   DIABETES

Identification and Characterization of GLP-1 Receptor-Expressing Cells Using a New Transgenic Mouse Model

(2013) P. Richards et al.   DIABETES

Pegylated Fgf21 rapidly normalizes insulin-stimulated glucose utilization in diet-induced insulin resistant mice

(2013) Raul C. Camacho et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

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

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

Efficacy and Safety of the Once-Daily GLP-1 Receptor Agonist Lixisenatide in Monotherapy: A randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono)

(2012) V. A. Fonseca et al.   DIABETES CARE

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

GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus

(2012) Juris J. Meier   Nature Reviews Endocrinology

Structure-based mutagenesis reveals the albumin-binding site of the neonatal Fc receptor

(2012) Jan Terje Andersen et al.   Nature Communications

Fc fusion to Glucagon-like peptide-1 inhibits degradation by human DPP-IV, increasing its half-life in serum and inducing a potent activity for human GLP-1 receptor activation

(2011) Dong-Myung Kim et al.   BMB Reports

Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides

(2011) Robert E. Steinert et al.   BRITISH JOURNAL OF NUTRITION

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

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

FGF21 Analogs of Sustained Action Enabled by Orthogonal Biosynthesis Demonstrate Enhanced Antidiabetic Pharmacology in Rodents

(2011) J. Mu et al.   DIABETES

Glucose-Dependent Insulinotropic Polypeptide: A Bifunctional Glucose-Dependent Regulator of Glucagon and Insulin Secretion in Humans

(2011) M. Christensen et al.   DIABETES

Benefits of Modest Weight Loss in Improving Cardiovascular Risk Factors in Overweight and Obese Individuals With Type 2 Diabetes

(2011) R. R. Wing et al.   DIABETES CARE

Encapsulation of Exenatide in Poly-(d,l-Lactide-Co-Glycolide) Microspheres Produced an Investigational Long-Acting Once-Weekly Formulation for Type 2 Diabetes

(2011) Mary Beth DeYoung et al.   Diabetes Technology & Therapeutics

State of the art in PEGylation: The great versatility achieved after forty years of research

(2011) Gianfranco Pasut et al.   JOURNAL OF CONTROLLED RELEASE

Comparison of sub-chronic metabolic effects of stable forms of naturally occurring GIP(1-30) and GIP(1-42) in high fat fed mice

(2011) V. A. Gault et al.   JOURNAL OF ENDOCRINOLOGY

Adipocyte expression of the glucose-dependent insulinotropic polypeptide receptor involves gene regulation by PPARγ and histone acetylation

(2011) Su-Jin Kim et al.   JOURNAL OF LIPID RESEARCH

The worldwide epidemiology of type 2 diabetes mellitus—present and future perspectives

(2011) Lei Chen et al.   Nature Reviews Endocrinology

A Better Anti-Diabetic Recombinant Human Fibroblast Growth Factor 21 (rhFGF21) Modified with Polyethylene Glycol

(2011) Zhifeng Huang et al.   PLoS One

The Glucagonostatic and Insulinotropic Effects of Glucagon-Like Peptide 1 Contribute Equally to Its Glucose-Lowering Action

(2010) K. J. Hare et al.   DIABETES

Glucose-Dependent Insulinotropic Polypeptide May Enhance Fatty Acid Re-esterification in Subcutaneous Abdominal Adipose Tissue in Lean Humans

(2010) M. Asmar et al.   DIABETES

Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein

(2010) Wolfgang Glaesner et al.   DIABETES-METABOLISM RESEARCH AND REVIEWS

Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review

(2010) J J Reilly et al.   INTERNATIONAL JOURNAL OF OBESITY

Importance of Neonatal FcR in Regulating the Serum Half-Life of Therapeutic Proteins Containing the Fc Domain of Human IgG1: A Comparative Study of the Affinity of Monoclonal Antibodies and Fc-Fusion Proteins to Human Neonatal FcR

(2010) Takuo Suzuki et al.   JOURNAL OF IMMUNOLOGY

GIP increases human adipocyte LPL expression through CREB and TORC2-mediatedtrans-activation of theLPLgene

(2010) Su-Jin Kim et al.   JOURNAL OF LIPID RESEARCH

Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial

(2010) Richard M Bergenstal et al.   LANCET

Persistence with injectable antidiabetic agents in members with type 2 diabetes in a commercial managed care organization

(2009) Catherine E. Cooke et al.   CURRENT MEDICAL RESEARCH AND OPINION

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

The recycling and transcytotic pathways for IgG transport by FcRn are distinct and display an inherent polarity

(2009) Salit Tzaban et al.   JOURNAL OF CELL BIOLOGY

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

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

PEGylation of Human Serum Albumin: Reaction of PEG-Phenyl-Isothiocyanate with Protein

(2008) Fantao Meng et al.   BIOCONJUGATE CHEMISTRY

Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes

(2008) P. V. Højberg et al.   DIABETOLOGIA

Caudal Brainstem Processing Is Sufficient for Behavioral, Sympathetic, and Parasympathetic Responses Driven by Peripheral and Hindbrain Glucagon-Like-Peptide-1 Receptor Stimulation

(2008) Matthew R. Hayes et al.   ENDOCRINOLOGY

Functional expression of glucose-dependent insulinotropic polypeptide receptors is coupled to differentiation in a human adipocyte model

(2008) R E Weaver et al.   INTERNATIONAL JOURNAL OF OBESITY

Treatment with the Dipeptidyl Peptidase-4 Inhibitor Vildagliptin Improves Fasting Islet-Cell Function in Subjects with Type 2 Diabetes

(2008) David A. D'Alessio et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

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

 -Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic   cells

(2008) N. Sonoda 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