Evidence mapPaperPMID 37246799Full record

ArticleDiabetes, obesity & metabolism2023

Circulating levels of proglucagon-derived peptides are differentially regulated by the glucagon-like peptide-1 agonist liraglutide and the centrally acting naltrexone/bupropion and can predict future weight loss and metabolic improvements: A 6-month long interventional study.

Konstantinos Stefanakis, Alexander Kokkinos, Georgia Argyrakopoulou, Sofia K Konstantinidou, Stamatia Simati, Matina Kouvari, Ajay Kumar, Bhanu Kalra, Melina Kumar, Nikolaos Bontozoglou and 2 more

Open access · greenAbstract read
In one paragraph

Article in Diabetes, obesity & metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 3 pooled it
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 3 syntheses or guidelines pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Article
  6. Review
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Konstantinos StefanakisDivision of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Boston VA Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-5512-2388
Alexander KokkinosFirst Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.ORCID 0000-0002-5491-2545
Georgia ArgyrakopoulouDiabetes and Obesity Unit, Athens Medical Center, Athens, Greece.ORCID 0000-0001-5502-565X
Sofia K KonstantinidouFirst Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Stamatia SimatiFirst Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Matina KouvariDivision of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Boston VA Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-1558-194X
Ajay KumarAnsh Labs, Webster, Texas, USA.
Bhanu KalraAnsh Labs, Webster, Texas, USA.
Melina KumarAnsh Labs, Webster, Texas, USA.
Nikolaos BontozoglouDepartment of Radiology, Athens Medical Center, Athens, Greece.
Konstantina KyriakopoulouDepartment of Radiology, Athens Medical Center, Athens, Greece.
Christos S MantzorosDivision of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Boston VA Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0003-3755-8158
Athens Medical Center · GRBeth Israel Deaconess Medical Center · USNational and Kapodistrian University of Athens · GR

Funding

NIDDK NIH HHS K24 DK081913
6 · The paper itself

Abstract

aimTo investigate the changes of circulating levels of all proglucagon-derived peptides (PGDPs) in individuals with overweight or obesity receiving liraglutide (3 mg) or naltrexone/bupropion (32/360 mg), and to explore the association between induced changes in postprandial PGDP levels and body composition, as well as metabolic variables, after 3 and 6 months on treatment. MATERIALS AND

methodsSeventeen patients with obesity or with overweight and co-morbidities, but without diabetes, were assigned to receive once-daily oral naltrexone/bupropion 32/360 mg (n = 8) or once-daily subcutaneous liraglutide 3 mg (n = 9). Participants were assessed before treatment initiation and after 3 and 6 months on treatment. At the baseline and 3-month visits, participants underwent a 3-hour mixed meal tolerance test to measure fasting and postprandial levels of PGDPs, C-peptide, hunger and satiety. Clinical and biochemical indices of metabolic function, magnetic resonance-assessed liver steatosis and ultrasound-assessed liver stiffness were measured at each visit.

resultsBoth medications improved body weight and composition, carbohydrate and lipid metabolism, and liver fat and function. Naltrexone/bupropion produced a weight-independent increase in the levels of proglucagon (P < .001) and decreases in glucagon-like peptide-2 (GLP-2), glucagon and the major proglucagon fragment (P ≤ .01), whereas liraglutide markedly upregulated total glucagon-like peptide-1 (GLP-1) levels in a weight-independent manner (P = .04), and similarly downregulated the major proglucagon fragment, GLP-2 and glucagon (P < .01). PGDP levels at the 3-month visit were positively and independently correlated with improvements in fat mass, glycaemia, lipaemia and liver function, and negatively with reductions in fat-free mass, at both the 3- and 6-month visits.

conclusionsPGDP levels in response to liraglutide and naltrexone/bupropion are associated with improvements in metabolism. Our study provides support for the administration of the downregulated members of the PGDP family as replacement therapy (e.g. glucagon), in addition to the medications currently in use that induced their downregulation (e.g. GLP-1), and future studies should explore whether the addition of other PGDPs (e.g. GLP-2) could offer additional benefits.

Indexed as

GlucagonGlucagon-Like Peptide 1BupropionGlucagon-Like Peptide 2Glucagon-Like PeptidesHumansLiraglutideNaltrexoneObesityOverweightPeptidesProglucagonWeight LossBupropionGlucagonGlucagon-Like Peptide 1Glucagon-Like Peptide 2Glucagon-Like PeptidesLiraglutideNaltrexonePeptidesProglucagonbupropionglicentinGLP-1glucagonliraglutidenaltrexoneobesityoxyntomodulinproglucagon-derived peptidesweight loss

Identifiers

PMID37246799
PMCPMC10524619
OpenAlexW4378640370

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.