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Diabetes, obesity and metabolism
The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update
Agnieszka Jakubowska, Carel W. le Roux, Adie Viljoen
Endocrinol Metab. 2024;39(1):12-22.   Published online February 14, 2024
DOI: https://doi.org/10.3803/EnM.2024.1942
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  • 214 Download
  • 1 Crossref
AbstractAbstract PDFPubReader   ePub   
Obesity is the fifth leading risk factor for global deaths with numbers continuing to increase worldwide. In the last 20 years, the emergence of pharmacological treatments for obesity based on gastrointestinal hormones has transformed the therapeutic landscape. The successful development of glucagon-like peptide-1 (GLP-1) receptor agonists, followed by the synergistic combined effect of glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists achieved remarkable weight loss and glycemic control in those with the diseases of obesity and type 2 diabetes. The multiple cardiometabolic benefits include improving glycemic control, lipid profiles, blood pressure, inflammation, and hepatic steatosis. The 2023 phase 2 double-blind, randomized controlled trial evaluating a GLP-1/GIP/glucagon receptor triagonist (retatrutide) in patients with the disease of obesity reported 24.2% weight loss at 48 weeks with 12 mg retatrutide. This review evaluates the current available evidence for GLP-1 receptor agonists, dual GLP-1/GIP receptor co-agonists with a focus on GLP-1/GIP/glucagon receptor triagonists and discusses the potential future benefits and research directions.

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  • New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review
    Jorge E. Jalil, Luigi Gabrielli, María Paz Ocaranza, Paul MacNab, Rodrigo Fernández, Bruno Grassi, Paulina Jofré, Hugo Verdejo, Monica Acevedo, Samuel Cordova, Luis Sanhueza, Douglas Greig
    International Journal of Molecular Sciences.2024; 25(8): 4407.     CrossRef
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Diabetes
A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans
Jack Alistair Sargeant, Joseph Henson, James Adam King, Thomas Yates, Kamlesh Khunti, Melanie Jane Davies
Endocrinol Metab. 2019;34(3):247-262.   Published online September 26, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.3.247
  • 11,554 View
  • 422 Download
  • 57 Web of Science
  • 59 Crossref
AbstractAbstract PDFPubReader   ePub   

Weight loss is an important goal in the management of several chronic conditions, including type 2 diabetes mellitus, and pharmacological therapies that aid weight loss are appealing. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are novel glucose-lowering therapies that have been shown to induce clinically significant reductions in body weight. However, this weight loss may not be attributed solely to fat mass (FM). Given the importance of skeletal muscle and lean body mass (LBM) on cardio-metabolic health and physical function, we reviewed the available literature reporting the effects of GLP-1RAs and SGLT2is on body composition. Results demonstrate that, in most circumstances, the weight loss associated with both therapies predominantly comprises a reduction in FM, although significant heterogeneity exists between studies. In over half of the studies identified, the proportion of LBM reduction ranged between 20% and 50% of total weight lost, which is consistent with diet-induced weight loss and bariatric surgery. No clear differences existed between GLP-1RAs and SGLT2is. Consequently, the loss of LBM and skeletal muscle associated with weight loss induced by GLP-1RAs and SGLT2is warrants attention. Strategies to preserve skeletal muscle and improve physical function, for example through structured exercise, are of great importance.

Citations

Citations to this article as recorded by  
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  • Once-weekly semaglutide administered after laparoscopic sleeve gastrectomy: Effects on body weight, glycemic control, and measured nutritional metrics in Japanese patients having both obesity and type 2 diabetes
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    ELISSA DRIGGIN, PARAG GOYAL
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    Daniel Lee, Jacqueline Capeau
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  • Marked weight loss on liraglutide 3.0 mg: Real‐life experience of a Swiss cohort with obesity
    Sara Santini, Nathalie Vionnet, Jérôme Pasquier, Elena Gonzalez‐Rodriguez, Montserrat Fraga, Nelly Pitteloud, Lucie Favre
    Obesity.2023; 31(1): 74.     CrossRef
  • Early type 2 diabetes treatment intensification with glucagon‐like peptide‐1 receptor agonists in primary care: An Australian perspective on guidelines and the global evidence
    Roy Rasalam, Sarah Abdo, Gary Deed, Richard O'Brien, Jane Overland
    Diabetes, Obesity and Metabolism.2023; 25(4): 901.     CrossRef
  • The effects of weight‐lowering pharmacotherapies on physical activity, function and fitness: A systematic review and meta‐analysis of randomized controlled trials
    Rishi Jobanputra, Jack A. Sargeant, Abdullah Almaqhawi, Ehtasham Ahmad, Franciskos Arsenyadis, David R. Webb, Louisa Y. Herring, Kamlesh Khunti, Melanie J. Davies, Thomas Yates
    Obesity Reviews.2023;[Epub]     CrossRef
  • Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation: a randomized controlled trial
    Rasmus M. Sandsdal, Christian R. Juhl, Simon B. K. Jensen, Julie R. Lundgren, Charlotte Janus, Martin B. Blond, Mads Rosenkilde, Adrian F. Bogh, Lasse Gliemann, Jens-Erik B. Jensen, Charalambos Antoniades, Bente M. Stallknecht, Jens J. Holst, Sten Madsbad
    Cardiovascular Diabetology.2023;[Epub]     CrossRef
  • Impact of novel glucose‐lowering therapies on physical function in people with type 2 diabetes: A systematic review and meta‐analysis of randomised placebo‐controlled trials
    Ehtasham Ahmad, Franciskos Arsenyadis, Abdullah Almaqhawi, Mary Barker, Rishi Jobanputra, Jack A. Sargeant, David R. Webb, Thomas Yates, Melanie J. Davies
    Diabetic Medicine.2023;[Epub]     CrossRef
  • Cancer cachexia as a blueprint for treating obesity
    Nikolai P. Jaschke, Tilman D. Rachner
    Trends in Endocrinology & Metabolism.2023; 34(7): 395.     CrossRef
  • The sun is rising on a new era of pharmacotherapy for obesity: some words of caution
    Peter N. Benotti, Bruce R. Bistrian
    Surgery for Obesity and Related Diseases.2023; 19(9): 1075.     CrossRef
  • Liraglutide Protects Against Diastolic Dysfunction and Improves Ventricular Protein Translation
    Cody Rutledge, Angela Enriquez, Kevin Redding, Mabel Lopez, Steven Mullett, Stacy L. Gelhaus, Michael Jurczak, Eric Goetzman, Brett A. Kaufman
    Cardiovascular Drugs and Therapy.2023;[Epub]     CrossRef
  • Effect of sodium-glucose transporter 2 inhibitors on sarcopenia in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
    Sha Zhang, Zhan Qi, Yidong Wang, Danfei Song, Deqiu Zhu
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Cysteine‐lowering treatment with mesna against obesity: Proof of concept and results from a human phase I, dose‐finding study
    Kathrine J. Vinknes, Thomas Olsen, Hasse Khiabani Zaré, Nasser E. Bastani, Emma Stolt, Anja F. Dahl, Roger D. Cox, Helga Refsum, Kjetil Retterstøl, Anders Åsberg, Amany Elshorbagy
    Diabetes, Obesity and Metabolism.2023; 25(11): 3161.     CrossRef
  • Repurposing Drugs for Diabetes Mellitus as Potential Pharmacological Treatments for Sarcopenia – A Narrative Review
    Miles D. Witham, Antoneta Granic, Ewan Pearson, Sian M. Robinson, Avan A. Sayer
    Drugs & Aging.2023; 40(8): 703.     CrossRef
  • Introduction to the dietary management of obesity in adults
    Vivian Lee
    Clinical Medicine.2023; 23(4): 304.     CrossRef
  • Efficacy and safety of the sodium‐glucose co‐transporter‐2 inhibitor empagliflozin in elderly Japanese adults (≥65 years) with type 2 diabetes: A randomized, double‐blind, placebo‐controlled, 52‐week clinical trial (EMPA‐ELDERLY)
    Daisuke Yabe, Kosuke Shiki, Gosuke Homma, Thomas Meinicke, Yuji Ogura, Yutaka Seino
    Diabetes, Obesity and Metabolism.2023; 25(12): 3538.     CrossRef
  • Independent Link Between Use of Mineralocorticoid Receptor Antagonists and Muscle Wasting in Heart Failure Patients Not Receiving Renin-Angiotensin System Inhibitors
    Ryo Numazawa, Satoshi Katano, Toshiyuki Yano, Ryohei Nagaoka, Katsuhiko Ohori, Hidemichi Kouzu, Suguru Honma, Yusuke Fujisawa, Kotaro Yamano, Arata Osanami, Masayuki Koyama, Akiyoshi Hashimoto, Masato Furuhashi
    Circulation Journal.2023; 88(1): 10.     CrossRef
  • Sodium-glucose co-transporter 2 inhibitors and Sarcopenia: A controversy that must be solved
    Baris Afsar, Rengin Elsurer Afsar
    Clinical Nutrition.2023; 42(12): 2338.     CrossRef
  • Oral semaglutide improves body composition and preserves lean mass in patients with type 2 diabetes: a 26-week prospective real-life study
    Sara Volpe, Giuseppe Lisco, Margherita Fanelli, Davide Racaniello, Valentina Colaianni, Valentina Lavarra, Domenico Triggiani, Lucilla Crudele, Vincenzo Triggiani, Carlo Sabbà, Giovanni De Pergola, Giuseppina Piazzolla
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  • The Effects of Sodium–Glucose Cotransporter 2 Inhibitors on Body Composition in Type 2 Diabetes Mellitus: A Narrative Review
    Soodeh Jahangiri, Mojtaba Malek, Sanjay Kalra, Mohammad E. Khamseh
    Diabetes Therapy.2023; 14(12): 2015.     CrossRef
  • Relationship between sodium–glucose cotransporter-2 inhibitors and muscle atrophy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
    Chengdong Xia, Yufeng Han, Chunhui Yin, Ruyue Geng, Zhenfei Liu, Yongle Du, Mingkun Yu
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  • The Role of Lifestyle Modification with Second-Generation Anti-obesity Medications: Comparisons, Questions, and Clinical Opportunities
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  • Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age
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  • Effect of Empagliflozin Versus Placebo on Body Fluid Balance in Patients With Acute Myocardial Infarction and Type 2 Diabetes Mellitus: Subgroup Analysis of the EMBODY Trial
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Original Articles
Miscellaneous
Effects of Serum Albumin, Calcium Levels, Cancer Stage and Performance Status on Weight Loss in Parathyroid Hormone-Related Peptide Positive or Negative Patients with Cancer
Ji-Yeon Lee, Namki Hong, Hye Ryun Kim, Byung Wan Lee, Eun Seok Kang, Bong-Soo Cha, Yong-ho Lee
Endocrinol Metab. 2018;33(1):97-104.   Published online March 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.1.97
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  • 8 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

A recent animal study showed that parathyroid hormone-related peptide (PTHrP) is associated with cancer cachexia by promoting adipose tissue browning, and we previously demonstrated that PTHrP predicts weight loss (WL) in patients with cancer. In this study, we investigated whether prediction of WL by PTHrP is influenced by clinical factors such as serum albumin, corrected calcium levels, cancer stage, and performance status (PS).

Methods

A cohort of 219 patients with cancer whose PTHrP level was measured was enrolled and followed for body weight (BW) changes. Subjects were divided into two groups by serum albumin (cutoff value, 3.7 g/dL), corrected calcium (cutoff value, 10.5 mg/dL), cancer stage (stage 1 to 3 or 4), or PS (Eastern Cooperative Oncology Group 0 to 1 or 2 to 4), respectively. Clinically significant WL was defined as either percent of BW change (% BW) <−5% or % BW <−2% plus body mass index (BMI) <20 kg/m2.

Results

After a median follow-up of 327 days, 74 patients (33.8%) experienced clinically significant WL. A positive PTHrP level was associated with a 2-fold increased risk of WL after adjusting for age, baseline BMI, serum albumin, corrected calcium level, cancer stage, and PS. The effect of PTHrP on WL remained significant in patients with low serum albumin, stage 4 cancer, and good PS. Regardless of calcium level, the effect of PTHrP on WL was maintained, although there was an additive effect of higher calcium and PTHrP levels.

Conclusion

Early recognition of patients with advanced cancer who are PTHrP positive with hypercalcemia or hypoalbuminemia is needed for their clinical management.

Citations

Citations to this article as recorded by  
  • Can Patients with Electrolyte Disturbances Be Safely and Effectively Treated in a Hospital-at-Home, Telemedicine-Controlled Environment? A Retrospective Analysis of 267 Patients
    Cohn May, Gueron Or, Segal Gad, Zubli Daniel, Hakim Hila, Fizdel Boris, Liber Pninit, Amir Hadar, Barkai Galia
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    Bahar Zehra Camurdanoglu Weber, Dilsad H. Arabaci, Serkan Kir
    Frontiers in Oncology.2022;[Epub]     CrossRef
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Effect of Weight Loss on Endothelial Function in Obese Premenopausal Women.
Se Woong Ma, Se Hwa Kim, Hyo Sung Nam, Kee Myoung Jung, Byung Hyun Yu, Yong Ju Lee, Seok O Park, Sung Kil Lim
J Korean Endocr Soc. 2006;21(6):506-514.   Published online December 1, 2006
DOI: https://doi.org/10.3803/jkes.2006.21.6.506
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AbstractAbstract PDF
BACKGROUND
Endothelial dysfunction, a pathological feature of obesity, can predict the occurrence of cardiovascular disease. The endothelial function was compared in obese, non-obese, and type 2 diabetic women, and the effect of weight loss on endothelial function in obese premenopausal women was also investigated. METHODS: Twenty type 2 diabetes patients, 35 obese and 20 non-obese non-diabetic subjects were recruited. Both the endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIV) were measured. The body composition, serum lipid, serum adiponectin and resistin were also measured. Weight loss in obese women was obtained by 6 months of calorific restriction, aerobic exercise and medication (sibutramine or orlistat). RESULTS: EDV was significantly impaired in the type 2 diabetes and obese groups compared to the control group (6.0 +/- 1.3% in diabetes group, 6.7 +/- 3.9% in obese group, 12.4 +/- 4.1% in control group, P < 0.01, respectively). The mean weight loss after 6 months was 8.5 +/- 3.2 kg (P < 0.001) in the obese group. There was a significant increase in EDV after weight loss (from 5.8 +/- 3.5% to 12.3 +/- 3.9%, P < 0.05). There was no change in EIV after weight loss. In addition, weight loss was associated with significant reductions in the levels of high-sensitivity C-reactive protein (hs-CRP) and serum triglyceride (P < 0.05, respectively). However, there were no significant changes in the serum adiponectin and resistin levels after weight loss. CONCLUSIONS: Our data demonstrated that weight loss was associated with improved endothelial function in obese premenopausal women, as assessed by brachial artery EDV and reduced hs-CRP.
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Case Report
A Case of Isolated ACTH Deficiency with Rapid Deterioration.
Sung Kwan Hong, Eun Joo Lee, Ki Soo Kim, Chul Ryong Lee, Hyung Joo Park, Hun Ho Song, Young Soo Lee
J Korean Endocr Soc. 1999;14(2):396-400.   Published online January 1, 2001
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AbstractAbstract PDF
Isolated ACTH deficiency is a rare disorder, and usually characterized by its chronic course. The 59 year-old woman patient who had been healthy until 2 months ago, admitted because of abdomial pain, general weakness and loss of weight about 12kg for 2 months. She looked a little pallor but color of skin was not remarkable. Blood pressure, serum electrolyte, and glucose on admission were within normal range. Serum calcium was elevated with the value of 12.6mg/dL, which was normalized after hydration. Cortisol response to RI induced hypoglycemia did not show any response. Anterior pituitary hormone except ACTH showed normal response during combined pituitary hormone stimulation test. These clinical and laboratory finding reveals that isolated ACTH deficiency was developed in a short term period. There were no abnormalities in sellar MRI except pineal cyst. Her complaints were disappeared dramatically after hydroccetisone replacement at 4th. hospital day. Here we report a case of isolated ACTH deficiency, which was rapidly developed, with hypercalcemia, abdominal pain, and loss of weight about 12kg for 2 months.
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Original Article
Effects of B3-adrenergic Receptor Gene Mutation on the Body Fat Distribution and Weight Loss in Obese Subjects.
Sung Kil Lim, Young Duk Song, Hyun Chul Lee, Kap Bum Huh, Kyung Rae Kim, Seok Won Park, Seok Joo Kwon, Eun Young Cho, Jong Ho Lee
J Korean Endocr Soc. 1998;13(4):590-600.   Published online January 1, 2001
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AbstractAbstract PDF
BACKGROUND
Recently, missense mutation of the B3-adrenergic receptor gene has been shown to be associated with early onset of type 2 diabetes, abdominal obesity and an increased capacity to gain weight. This study was performed to investigate the effects of Trp64Arg mutation in the B3-adrenergic receptor gene on body fat distribution and weight loss in obese subjects. METHODS: Determination of the B3-adrenergic receptor gene mutation with restriction enzyme digestion method, anthropometry, various biochemical studies, including oral glucose tolerance test were performed in 99 obese and 35 control subjects. Body fat distributions were also evaluated by computerized tomography before and after weight-reduction program. RESULTS: I) There were no differences in the frequencies of Trp64Arg mutation in the B3-adrenergic receptor gene between obese and control subjects (15.2 vs 12.9 %). 2) The obese subjects with Trp64Arg mutation had higher waist to hip circumference ratio(WHR) (0.93 +/- 0.05 vs 0.87 +/- 0.04, p<0.001), visceral fat area (115.0 +/- 25.9 vs 86.4 +/- 41.4 cm, p=0.01), but decreased plasma free fatty acid (618.0 +/- 163.1 vs 817.5 +/- 248.2 pEq/L, p=0.001), and triglyceride level (118.7 +/- 36.2 vs 158.4 +/- 105.8 mg/dL, p=0.015) than those without mutation. 3) The obese subjects with Trp64Arg mutation had smaller decreases in weight (-3.4 vs -5.1 kg, p<0.001), body fat content (-2.1 vs -3.8 %, p<0.001), WHR (-0.01 vs -0.03, p=0.025), and abdominal fat masses (total, subcutaneous, and visceral fat) after weight-reduction program than those without mutation. CONCLUSION: Trp64Arg mutation in the B3-adrenergic receptor gene might be one of genetic loci contributing to central obesity and a predictor of difficulty in losing weight in obese subjects.
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Endocrinol Metab : Endocrinology and Metabolism