Trial reportAdvances in therapy2024

Glucagon-Like Peptide 1 (GLP-1) Receptor Variants and Glycemic Response to Liraglutide: A Pharmacogenetics Study in Iranian People with Type 2 Diabetes Mellitus.

Maryam Eghbali, Fariba Alaei-Shahmiri, Nahid Hashemi-Madani, Zahra Emami, Ladan Mostafavi, Mojtaba Malek, Mohammad E Khamseh

Abstract readEquivalence TrialRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Advances in therapy, 2024. The graph read 2 numbers from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. Cited by 9 papers, 1 of them a synthesis that pooled it.

2numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

Read, but not usablea number the graph found but could not read as for or against

Glycemic controlcomparator not stated · t2dfeeds one cell of the map
OR 2.521.03 to 6.13P = 0.04
In genetic models, rs10305420 T allele homozygosity was associated with optimal glycemic response to liraglutide compared with heterozygous and wild-type homozygous states (recessive model: OR 3.28, 95% CI 1.41-7.65, P = 0.006; codominant model: OR 2.52, 95% CI 1.03-6.13, P = 0.04).
Glycemic controlcomparator not stated · t2dfeeds one cell of the map
OR 3.281.41 to 7.65P = 0.006
In genetic models, rs10305420 T allele homozygosity was associated with optimal glycemic response to liraglutide compared with heterozygous and wild-type homozygous states (recessive model: OR 3.28, 95% CI 1.41-7.65, P = 0.006; codominant model: OR 2.52, 95% CI 1.03-6.13, P = 0.04).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

GLP-1 receptor agonists×glycemic control

No readable resultOpen on the map →What to test next →

40 readable studies in this cell: 89 favour the treatment, 16 find no difference, 10 favour the comparator.

Belief with this paper
0.90replicated · 63 families support, 7 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017204463,297 enrolled · 2013
Δ -0.66-0.80 to -0.52
NCT036893742,274 enrolled · 2018
Δ -0.29-0.38 to -0.20
NCT039879191,879 enrolled · 2019
Δ -0.51-0.64 to -0.38
NCT026078651,864 enrolled · 2016
Δ -0.50-0.60 to -0.40
NCT013360231,663 enrolled · 2011
Treatment contrast -0.64-0.75 to -0.53
NCT040178321,441 enrolled · 2019
Δ -0.20-0.30 to -0.10
NCT018365231,398 enrolled · 2013
Δ -0.20-0.32 to -0.07
NCT019301881,231 enrolled · 2013
Δ -1.06-1.21 to -0.91
NCT007344741,202 enrolled · 2008
Δ -0.71-0.87 to -0.55
NCT020581471,170 enrolled · 2014
Δ -0.29-0.38 to -0.19
NCT003184611,091 enrolled · 2006
Δ -1.09-1.30 to -0.88
NCT021289321,089 enrolled · 2014
Δ -0.81-0.96 to -0.67

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · 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.

5 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

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

Corrections and comments

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

7 · Who and what money

Authors and funding

7 authors.

Maryam Eghbali *Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.
Fariba Alaei-Shahmiri *Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.
Nahid Hashemi-MadaniEndocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.
Zahra EmamiEndocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.
Ladan MostafaviEndocrine Research Center, Institute of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Mojtaba MalekResearch Center for Prevention of Cardiovascular Disease, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.
Mohammad E KhamsehEndocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran. khamseh.m@iums.ac.ir.ORCID http://orcid.org/0000-0003-4313-8440

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

introductionPharmacogenetics studies suggest that genetic variants have a possible influence on the inter-individual differences in therapeutic response to glucagon-like peptide 1 receptor agonists (GLP-1 RAs). We aimed to examine the potential role of genetic variability of glucagon-like peptide 1 receptor (GLP-1R) on glycemic response to GLP-1 RAs in a population of Iranian people with type 2 diabetes mellitus (T2DM).

methodsIn this study, we analyzed the data from participants in a non-inferiority randomized clinical trial between 2019 and 2020. Patients received liraglutide 1.8 mg/day subcutaneously for 24 weeks. They were stratified by the baseline hemoglobin A1c (HbA1c) into four categories: 7-7.99, 8-8.99, 9-9.99, and ≥ 10%. In each category, subjects with HbA1c reduction greater than the median ΔHbA1c value for that group were defined as optimal responders. The pooled number of optimal/suboptimal responders in the four groups was used for the comparison. We evaluated two genetic variants of GLP-1R, rs6923761 and rs10305420, using Sanger sequencing. Logistic regression analyses were performed to examine the associations of the GLP-1R variants with the glycemic response in different genetic models.

resultsOut of 233 participants, 120 individuals were optimal responders. Median HbA1c reduction was - 2.5% in the optimal responder group compared with - 1.0% in the suboptimal responder group (P < 0.001). In genetic models, rs10305420 T allele homozygosity was associated with optimal glycemic response to liraglutide compared with heterozygous and wild-type homozygous states (recessive model: OR 3.28, 95% CI 1.41-7.65, P = 0.006; codominant model: OR 2.52, 95% CI 1.03-6.13, P = 0.04). No significant association was found between rs6923761 variant and HbA1c reduction.

conclusionGLP-1R rs10305420 polymorphism can explain some of the inter-individual differences in glycemic response to liraglutide in a population of Iranian people with T2DM.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsLiraglutideMiddle Eastern PeopleGlucagon-Like Peptide 1Glycated HemoglobinHumansIranPharmacogeneticsGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsGlycated HemoglobinHypoglycemic AgentsLiraglutideGLP-1 receptor agonistsGLP-1 receptor variantsGlycemic responseType 2 diabetes mellitus

Identifiers

PMID38172377

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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 OpenQuestion graph.