Literature DB >> 31177183

Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study.

Preeshila Behary1, George Tharakan1, Kleopatra Alexiadou1, Nicholas Johnson2, Nicolai J Wewer Albrechtsen3,4, Julia Kenkre1, Joyceline Cuenco1, David Hope1, Oluwaseun Anyiam1, Sirazum Choudhury1, Haya Alessimii1, Ankur Poddar1, James Minnion1, Chedie Doyle1, Gary Frost1, Carel Le Roux1,5, Sanjay Purkayastha6, Krishna Moorthy6, Waljit Dhillo1, Jens J Holst7, Ahmed R Ahmed6, A Toby Prevost2, Stephen R Bloom1, Tricia M Tan8.   

Abstract

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity. RESEARCH DESIGN AND METHODS: In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (n = 15) or saline (n = 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were 1) body weight, 2) fructosamine levels, 3) glucose and insulin during a mixed meal test (MMT), 4) energy expenditure (EE), 5) energy intake (EI), and 6) mean glucose and measures of glucose variability during continuous glucose monitoring.
RESULTS: GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (P = 0.025) with GOP (mean change -4.4 [95% CI -5.3, -3.5] kg) versus saline (-2.5 [-4.1, -0.9] kg). GOP led to a greater improvement (P = 0.0026) in fructosamine (-44.1 [-62.7, -25.5] µmol/L) versus saline (-11.7 [-18.9, -4.5] µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD.
CONCLUSIONS: GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.
© 2019 by the American Diabetes Association.

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Year:  2019        PMID: 31177183     DOI: 10.2337/dc19-0449

Source DB:  PubMed          Journal:  Diabetes Care        ISSN: 0149-5992            Impact factor:   19.112


  20 in total

Review 1.  Bariatric Surgery in the Treatment of Type 2 Diabetes.

Authors:  Alison H Affinati; Nazanene H Esfandiari; Elif A Oral; Andrew T Kraftson
Journal:  Curr Diab Rep       Date:  2019-12-04       Impact factor: 4.810

2.  Length of biliopancreatic limb in Roux-en-Y gastric bypass and its impact on post-operative outcomes in metabolic and obesity surgery-systematic review and meta-analysis.

Authors:  Anna Kamocka; Swathikan Chidambaram; Simon Erridge; Gauri Vithlani; Alexander Dimitri Miras; Sanjay Purkayastha
Journal:  Int J Obes (Lond)       Date:  2022-08-04       Impact factor: 5.551

3.  Vertical sleeve gastrectomy induces enteroendocrine cell differentiation of intestinal stem cells through bile acid signaling.

Authors:  Ki-Suk Kim; Bailey Ce Peck; Yu-Han Hung; Kieran Koch-Laskowski; Landon Wood; Priya H Dedhia; Jason R Spence; Randy J Seeley; Praveen Sethupathy; Darleen A Sandoval
Journal:  JCI Insight       Date:  2022-06-08

4.  Targeting the Enteroendocrine System for Treatment of Obesity.

Authors:  Emily L Miedzybrodzka; Fiona M Gribble; Frank Reimann
Journal:  Handb Exp Pharmacol       Date:  2022

5.  Effect of left gastric artery embolization on obesity and ghrelin/leptin levels in pigs.

Authors:  Hui Liu; Xiangying Li; Rihui Chen; Dingcheng Liu; Chao Tong
Journal:  Am J Transl Res       Date:  2021-05-15       Impact factor: 4.060

Review 6.  Leveraging the Gut to Treat Metabolic Disease.

Authors:  Ruth E Gimeno; Daniel A Briere; Randy J Seeley
Journal:  Cell Metab       Date:  2020-03-17       Impact factor: 27.287

Review 7.  Gastrointestinal Peptides as Therapeutic Targets to Mitigate Obesity and Metabolic Syndrome.

Authors:  Kleopatra Alexiadou; Tricia M-M Tan
Journal:  Curr Diab Rep       Date:  2020-05-21       Impact factor: 4.810

Review 8.  Proglucagon-Derived Peptides as Therapeutics.

Authors:  Ryan A Lafferty; Finbarr P M O'Harte; Nigel Irwin; Victor A Gault; Peter R Flatt
Journal:  Front Endocrinol (Lausanne)       Date:  2021-05-18       Impact factor: 5.555

9.  Proglucagon peptide secretion profiles in type 2 diabetes before and after bariatric surgery: 1-year prospective study.

Authors:  Kleopatra Alexiadou; Joyceline Cuenco; James Howard; Nicolai Jacob Wewer Albrechtsen; Ibiyemi Ilesanmi; Anna Kamocka; George Tharakan; Preeshila Behary; Paul R Bech; Ahmed R Ahmed; Sanjay Purkayastha; Robert Wheller; Matthieu Fleuret; Jens Juul Holst; Stephen R Bloom; Bernard Khoo; Tricia M-M Tan
Journal:  BMJ Open Diabetes Res Care       Date:  2020-03

10.  Oxyntomodulin May Distinguish New-Onset Diabetes After Acute Pancreatitis From Type 2 Diabetes.

Authors:  Sakina H Bharmal; Jaelim Cho; Charlotte E Stuart; Gisselle C Alarcon Ramos; Juyeon Ko; Maxim S Petrov
Journal:  Clin Transl Gastroenterol       Date:  2020-02       Impact factor: 4.396

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