4.7 Review

GLP-1 physiology informs the pharmacotherapy of obesity

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Endocrinology & Metabolism

The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity

Martin Friedrichsen et al.

Summary: This study investigated the effects of once-weekly subcutaneous semaglutide 2.4 mg on gastric emptying, appetite, and energy intake in adults with obesity. The results showed that semaglutide significantly suppressed appetite, improved control of eating, and reduced food cravings, ad libitum energy intake, and body weight compared to placebo. However, there was no evidence of delayed gastric emptying with semaglutide at week 20.

DIABETES OBESITY & METABOLISM (2021)

Review Endocrinology & Metabolism

Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation

Brent A. McLean et al.

Summary: GLP-1 is produced in gut endocrine cells and in the brain to regulate islet function, satiety, and gut motility. However, there are challenges in determining direct vs indirect actions of GLP-1, as well as the technical difficulty in reliable detection of GLP-1R.

ENDOCRINE REVIEWS (2021)

Article Medicine, General & Internal

Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial

Thomas A. Wadden et al.

Summary: This study compared the effects of once-weekly subcutaneous semaglutide with placebo as an adjunct to intensive behavioral therapy and initial low-calorie diet for weight management in adults with overweight or obesity. The results showed that semaglutide led to significantly greater weight loss compared to placebo over 68 weeks, with a higher proportion of participants achieving weight loss goals. More research is needed to evaluate the long-term effectiveness of this treatment.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)

Article Medicine, General & Internal

Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, doubleblind, double-dummy, placebo-controlled, phase 3 trial

Melanie Davies et al.

Summary: In this study, once-weekly subcutaneous semaglutide 2.4 mg was shown to achieve a significantly greater and clinically meaningful weight reduction compared to placebo in adults with overweight or obesity and type 2 diabetes. Adverse events, particularly gastrointestinal events, were more common with semaglutide compared to placebo.

LANCET (2021)

Article Medicine, General & Internal

Once-Weekly Semaglutide in Adults with Overweight or Obesity

John P. H. Wilding et al.

Summary: The study demonstrates that for individuals with obesity, once-weekly use of 2.4 mg semaglutide in combination with lifestyle intervention can lead to sustained and clinically relevant weight loss, with significant improvements in cardiometabolic risk factors and physical functioning reported by participants.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Pharmacology & Pharmacy

Clinical Pharmacokinetics of Oral Semaglutide: Analyses of Data from Clinical Pharmacology Trials

Rune V. Overgaard et al.

Summary: A population pharmacokinetic model was used to investigate the absorption, distribution, and elimination of oral semaglutide for treating type 2 diabetes. The model accurately described concentration profiles across trials, with factors such as post-dose fasting time and body weight affecting semaglutide exposure. Despite relatively high within-subject variability in oral bioavailability, it was reduced considerably at steady state.

CLINICAL PHARMACOKINETICS (2021)

Review Endocrinology & Metabolism

Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials

Naveed Sattar et al.

Summary: The meta-analysis showed that GLP-1 receptor agonists can reduce the risk of major adverse cardiovascular events, all-cause mortality, hospital admission for heart failure, and worsening kidney function in patients with type 2 diabetes, regardless of structural homology.

LANCET DIABETES & ENDOCRINOLOGY (2021)

Article Medicine, General & Internal

Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial

Domenica Rubino et al.

Summary: Continuing treatment with semaglutide resulted in greater weight loss maintenance and improvement in other physical indicators compared to switching to placebo over a 48-week period in adults with overweight or obesity. The study also found that gastrointestinal events were more common with continued semaglutide, but discontinuation rates were similar between the two groups.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)

Article Medicine, General & Internal

Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial

Lone B. Enebo et al.

Summary: The study aimed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the combination of Cagrilintide and Semaglutide for weight management. Results showed that concomitant treatment with Cagrilintide and Semaglutide was well tolerated with an acceptable safety profile. Larger and longer trials are needed to fully assess the efficacy and safety of this treatment combination.

LANCET (2021)

Article Neurosciences

Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting

Nasim Biglari et al.

Summary: Biglari et al. discovered distinct subgroups of POMC neurons in the arcuate nucleus, each with unique molecular signatures and regulatory functions in feeding, revealing new insights into body weight control mechanisms.

NATURE NEUROSCIENCE (2021)

Article Medicine, General & Internal

A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis

Philip N. Newsome et al.

Summary: This phase 2 trial demonstrated that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution compared to placebo in patients with NASH, but did not show a significant between-group difference in the percentage of patients with an improvement in fibrosis stage.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Medicine, General & Internal

Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined

Julie R. Lundgren et al.

Summary: A strategy combining exercise and liraglutide therapy improved healthy weight loss maintenance more than either treatment alone. The combination strategy led to greater weight loss and improvements in metabolic health-related indicators.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Cell Biology

Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism

Diba Borgmann et al.

Summary: Distinct gut-innervating sensory neurons play differential roles in controlling feeding and glucoregulation, with some vagal afferents influencing meal termination and glucose tolerance through GLP1R activation, while others mainly regulate hepatic glucose production and normoglycemia through GPR65 expression.

CELL METABOLISM (2021)

Article Endocrinology & Metabolism

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

Tito Borner et al.

Summary: GIPR signaling blocks emesis and attenuates illness behaviors induced by GLP-1R activation while maintaining reduced food intake, weight loss, and improved glucose tolerance. The hindbrain AP/NTS is crucial for processing GLP-1R ligand-induced effects on food intake and weight suppression, as well as emetic stimuli.

DIABETES (2021)

Article Chemistry, Medicinal

Development of Cagrilintide, a Long-Acting Amylin Analogue

Thomas Kruse et al.

Summary: This article presents the development of a stable, lipidated long-acting amylin analogue called cagrilintide, which has shown significant weight loss effects in clinical trials, either alone or in combination with the GLP-1 analogue semaglutide. Adjustment of structure-activity relationships led to the selection of cagrilintide for clinical development as a treatment for obesity.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Medicine, General & Internal

Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes

Juan P. Frias et al.

Summary: The study showed that Tirzepatide was both noninferior and superior to Semaglutide in terms of the mean change in glycated hemoglobin levels for patients with type 2 diabetes over 40 weeks. Additionally, reductions in body weight were greater with Tirzepatide compared to Semaglutide, with similar rates of gastrointestinal adverse events reported in both groups.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Medicine, General & Internal

Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes

Hertzel C. Gerstein et al.

Summary: The trial compared the cardiovascular and renal outcomes of weekly injections of efpeglenatide versus a placebo in participants with type 2 diabetes and a history of cardiovascular disease or current kidney disease. The study found that the risk of cardiovascular events was lower with efpeglenatide treatment, and a composite renal outcome event was also reduced.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Medicine, Research & Experimental

GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice

Ricardo J. Samms et al.

Summary: Tirzepatide, a dual GIP and GLP-1 receptor agonist, improves insulin sensitivity in obese mice to a greater extent than GLP-1R agonism. This effect is associated with enhanced glucose disposal in white adipose tissue and reduction of branched-chain amino acids in the circulation. The upregulation of genes related to the catabolism of glucose, lipid, and BCAAs in brown adipose tissue contributes to the improved insulin sensitivity by tirzepatide.

JOURNAL OF CLINICAL INVESTIGATION (2021)

Article Endocrinology & Metabolism

A genetic map of the mouse dorsal vagal complex and its role in obesity

Mette Q. Ludwig et al.

Summary: The study indicates that DVC neuronal populations associated with obesity predisposition can suppress feeding, making them potential therapeutic targets for obesity treatment. By activating some of these neuronal populations, feeding in rodents can be decreased, highlighting their importance in regulating energy balance.

NATURE METABOLISM (2021)

Article Endocrinology & Metabolism

Central and peripheral GLP-1 systems independently suppress eating

Daniel I. Brierley et al.

Summary: GLP-1 suppresses eating through independent gut-brain circuits, with PPG(NTS) neurons not being necessary for the eating suppression effects of GLP-1 receptor agonists. Concurrent activation of PPG(NTS) neurons can more effectively suppress eating than using semaglutide alone.

NATURE METABOLISM (2021)

Article Endocrinology & Metabolism

Efficacy and safety of glucagon-like peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with obesity without type 2 diabetes mellitus: A randomized dose-ranging study

Maria Alba et al.

Summary: JNJ-64565111 significantly reduced body weight in individuals with obesity but was associated with a higher incidence of treatment-emergent adverse events.

CLINICAL OBESITY (2021)

Article Endocrinology & Metabolism

Efficacy and safety of glucagon-like peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with type 2 diabetes mellitus and obesity: A randomized dose-ranging study

Nicholas A. Di Prospero et al.

Summary: The study demonstrated that JNJ-64565111 significantly reduced body weight in a dose-dependent manner, but was associated with a higher incidence of treatment-emergent adverse events, no reduction in HbA1c, and increased levels of fasting plasma glucose and insulin.

CLINICAL OBESITY (2021)

Article Biotechnology & Applied Microbiology

Advances in oral peptide therapeutics

Daniel J. Drucker

NATURE REVIEWS DRUG DISCOVERY (2020)

Article Cardiac & Cardiovascular Systems

Liraglutide decreases energy expenditure and does not affect the fat fraction of supraclavicular brown adipose tissue in patients with type 2 diabetes

Huub J. van Eyk et al.

NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES (2020)

Article Medicine, General & Internal

A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity

Aaron S. Kelly et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Article Medicine, General & Internal

Obesity in adults: a clinical practice guideline

Sean Wharton et al.

CANADIAN MEDICAL ASSOCIATION JOURNAL (2020)

Article Medicine, Research & Experimental

Semaglutide lowers body weight in rodents via distributed neural pathways

Sanaz Gabery et al.

JCI INSIGHT (2020)

Article Medicine, General & Internal

Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

Mansoor Husain et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

Article Medicine, Research & Experimental

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

Daniel J. Drucker et al.

JOURNAL OF CLINICAL INVESTIGATION (2017)

Article Endocrinology & Metabolism

The glucagon-like peptide-1 receptor in the ventromedial hypothalamus reduces short-term food intake in male mice by regulating nutrient sensor activity

Melissa A. Burmeister et al.

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM (2017)

Article Endocrinology & Metabolism

Knockdown of GLP-1 Receptors in Vagal Afferents Affects Normal Food Intake and Glycemia

Jean-Philippe Krieger et al.

DIABETES (2016)

Article Endocrinology & Metabolism

Glucagon increases energy expenditure independently of brown adipose tissue activation in humans

V. Salem et al.

DIABETES OBESITY & METABOLISM (2016)

Article Physiology

Role of lateral septum glucagon-like peptide 1 receptors in food intake

Sarah J. Terrill et al.

AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY (2016)

Review Cell Biology

The Cardiovascular Biology of Glucagon-like Peptide-1

Daniel J. Drucker

CELL METABOLISM (2016)

Article Neurosciences

Astrocytes Regulate GLP-1 Receptor-Mediated Effects on Energy Balance

David J. Reiner et al.

JOURNAL OF NEUROSCIENCE (2016)

Article Medicine, General & Internal

Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes The SCALE Diabetes Randomized Clinical Trial

Melanie J. Davies et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2015)

Article Medicine, General & Internal

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

Xavier Pi-Sunyer et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

Article Endocrinology & Metabolism

GLP-1 Receptor Activation Modulates Appetite- and Reward-Related Brain Areas in Humans

Liselotte van Bloemendaal et al.

DIABETES (2014)

Article Medicine, Research & Experimental

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

Anna Secher et al.

JOURNAL OF CLINICAL INVESTIGATION (2014)

Article Endocrinology & Metabolism

Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt

Laura E. Rupprecht et al.

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM (2013)

Article Cardiac & Cardiovascular Systems

A Glucagon-Like Peptide-1 Analog Reverses the Molecular Pathology and Cardiac Dysfunction of a Mouse Model of Obesity

Mohammad Hossein Noyan-Ashraf et al.

CIRCULATION (2013)

Article Multidisciplinary Sciences

Glucagon-like peptide 1 receptor induced suppression of food intake, and body weight is mediated by central IL-1 and IL-6

Rozita Shirazi et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

Article Biochemistry & Molecular Biology

A Novel Human-Based Receptor Antagonist of Sustained Action Reveals Body Weight Control by Endogenous GLP-1

James T. Patterson et al.

ACS CHEMICAL BIOLOGY (2011)

Article Physiology

Brain activation following peripheral administration of the GLP-1 receptor agonist exendin-4

Elena-Dana Baraboi et al.

AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY (2011)

Article Neurosciences

Glucagon-Like Peptide 1 Receptors in Nucleus Accumbens Affect Food Intake

Amanda M. Dossat et al.

JOURNAL OF NEUROSCIENCE (2011)

Article Endocrinology & Metabolism

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

Alessandro Pocai et al.

DIABETES (2009)

Article Biochemistry & Molecular Biology

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

Jonathan W. Day et al.

NATURE CHEMICAL BIOLOGY (2009)

Article Cell Biology

The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting

Christine Longuet et al.

CELL METABOLISM (2008)

Article Medicine, Research & Experimental

Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure

Tanya Hansotia et al.

JOURNAL OF CLINICAL INVESTIGATION (2007)

Article Endocrinology & Metabolism

Leptin regulation of the anorexic response to glucagon-like peptide-1 receptor stimulation

Diana L. Williams et al.

DIABETES (2006)