Trial reportDiabetes, obesity & metabolism2022

Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ß-cell function in people with type 2 diabetes.

Ele Ferrannini, Elisabeth Niemoeller, Terry Dex, Soraly Servera, Andrea Mari

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2022. The graph read 1 number from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. It reports registered trial NCT02787551. Cited by 5 papers.

1number the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.5field-weighted citation impact, top 16% 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.

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

Glycemic controlcomparator not stated · obesity, t2dfeeds one cell of the map
increase 35.0p = .0032
GLP-1RA), while β-cell glucose sensitivity increased by a median 35% (p = .0032 vs.

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: 97 favour the treatment, 16 find no difference, 10 favour the comparator.

Belief with this paper
0.91replicated · 68 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.

NCT02787551 phase3completed

A 26-Week Randomized, Open-label, Active Controlled, Parallel-group, Study Assessing the Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination in Adults With Type 2 Diabetes Inadequately Controlled on GLP-1 Receptor Agonist and Metformin (Alone or With Pioglitazone and/or SGLT2 Inhibitors), Followed by a Fixed Ratio Combination Single-arm 26-Week Extension Period

Ran2016Enrolled514Registered outcomes18Posted comparisons6ConditionsType 2 Diabetes MellitusArmsalbiglutide, Background therapy: Oral Anti-diabetic Drug (Metformin, Pioglitazone, SGLT2 inhibitor), Dulaglutide, exenatide, Exenatide extended-release
Open the trial in the graph
5 · Its place in the literature

Who cites it

5 citing papers in PubMed, 12 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Review
  5. 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

5 authors at 4 institutions in 3 countries.

Ele FerranniniCNR Institute of Clinical Physiology, Pisa, Italy.ORCID 0000-0002-1384-1584
Elisabeth NiemoellerSanofi, Frankfurt, Germany.
Terry DexSanofi US, Bridgewater, New Jersey, USA.
Soraly ServeraSanofi US, Bridgewater, New Jersey, USA.
Andrea MariCNR Institute of Neuroscience, Padua, Italy.
Sanofi (United States) · USIstituto di Fisiologia Clinica · ITNeuroscience Institute · ITSanofi (Germany) · DE

Funding

Sanofi
8 · The paper itself

Abstract

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

aimMultiple studies support the efficacy of combining a glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in people with type 2 diabetes inadequately controlled on dual/triple oral therapy. Fixed-ratio combinations of basal insulin + GLP-1RA represent a further advance to facilitate management. We assessed the impact of fixed-ratio combination basal insulin + GLP-1RA treatment on β-cell function. MATERIALS AND

methodsWe analysed data from 351 participants in the LixiLan-G trial (NCT02787551) randomized to receive iGlarLixi (insulin glargine 100 U/ml + lixisenatide) or to continue daily/weekly GLP-1RA, both on top of metformin. Participants received a 2-h meal tolerance test before randomization and at study end (26 weeks), with timed plasma glucose and C-peptide determinations. β-cell function parameters were resolved using mathematical modelling.

resultsIn the GLP-1RA group (n = 162), both body weight and glycated haemoglobin decreased at week 26, yet none of the insulin secretion/β-cell function parameters changed significantly. In contrast, in the iGlarLixi group (n = 189), glycated haemoglobin decreased significantly more than in the GLP-1RA group (p < .0001) despite an increase in body weight (+1.7 ± 3.9 kg, p < .0001). Fasting and stimulated insulin secretion decreased at Week 26 (both p < .0001 vs. GLP-1RA), while β-cell glucose sensitivity increased by a median 35% (p = .0032 vs. GLP-1RA). The incremental meal tolerance test glucose area showed a larger reduction with iGlarLixi versus GLP-1RA (p < .0001).

conclusionsIn people with type 2 diabetes on metformin, 26-week treatment with iGlarLixi resulted in a marked improvement in β-cell function concomitant with sparing of endogenous insulin release and a reduction in meal absorption.

Indexed as

Diabetes Mellitus, Type 2MetforminBlood GlucoseBody WeightDrug CombinationsGlucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like Peptide-2 ReceptorGlycated HemoglobinHumansHypoglycemic AgentsInsulinInsulin GlarginePeptidesBlood GlucoseDrug CombinationsGlucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like Peptide-2 ReceptorGlycated HemoglobinHypoglycemic AgentsInsulinInsulin GlarginelixisenatideMetforminPeptidesglucagon-like peptide 1 receptor agonistiGlarLixiinsulin secretionmixed-meal tolerance testβ-cell function

Identifiers

PMID35257461
PMCPMC9314929
OpenAlexW4220949169

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
Read underepoch 390

Registered trials

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.