Trial reportDiabetes, obesity & metabolism2023

Bexagliflozin as an adjunct to metformin for the treatment of type 2 diabetes in adults: A 24-week, randomized, double-blind, placebo-controlled trial.

Yuan-Di Halvorsen, Annie L Conery, John Paul Lock, Wenjiong Zhou, Mason W Freeman

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2023. The graph read 7 numbers from its abstract, feeding 8 cells of the map: it supports the treatment in 6, favours the comparator in 2. Cited by 8 papers.

7numbers the graph read from it
8cells of the map it votes in
8citing papers in PubMed
3.2field-weighted citation impact, top 7% 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.

← favours the treatmentfavours the comparator →
-9.830 · no effect
Change in glycated haemoglobin (HbA1c) from baseline to week 24bexagliflozin plus metformin vs placebo plus metforminfavours the treatment · t2dfeeds 2 cells of the map
Δ -0.53-0.74 to -0.32< .0001
RESULTS: The mean change in HbA1c was -1.09% (95% CI -1.24%, -0.94%) in the bexagliflozin arm and -0.56% (-0.71%, -0.41%) in the placebo arm, a difference of -0.53% (-0.74%, -0.32%; p < .0001).
Fasting plasma glucosebexagliflozin plus metformin vs placebo plus metforminfavours the treatment · t2dfeeds 2 cells of the map
Δ -1.35-1.83 to -0.86< .0001
Placebo-adjusted changes from baseline SBP, fasting plasma glucose and body mass were -7.07 mmHg (-9.83, -4.32; p < .0001), -1.35 mmol/L (-1.83, -0.86; p < .0001) and -2.51 kg (-3.45, -1.57; p < .0001).
Systolic blood pressure (SBP)bexagliflozin plus metformin vs placebo plus metforminfavours the treatment · t2dfeeds 2 cells of the map
Δ -7.07-9.83 to -4.32< .0001
Placebo-adjusted changes from baseline SBP, fasting plasma glucose and body mass were -7.07 mmHg (-9.83, -4.32; p < .0001), -1.35 mmol/L (-1.83, -0.86; p < .0001) and -2.51 kg (-3.45, -1.57; p < .0001).
Change in glycated haemoglobin (HbA1c) from baseline to week 24bexagliflozin plus metformin vs placebo plus metforminfavours the treatment · t2dfeeds 2 cells of the map
Δ -0.70-0.92 to -0.48< .0001
Excluding observations after rescue medication, the intergroup difference was -0.70% (-0.92, -0.48; p < .0001).

The authors add: Excluding observations after rescue medication

Glycemic controlfavours the treatment · against placebo · t2dfeeds one cell of the map
mean change -1.09-1.24 to -0.94
RESULTS: The mean change in HbA1c was -1.09% (95% CI -1.24%, -0.94%) in the bexagliflozin arm and -0.56% (-0.71%, -0.41%) in the placebo arm, a difference of -0.53% (-0.74%, -0.32%; p < .0001).
Body massbexagliflozin plus metformin vs placebo plus metforminfavours the treatment · t2dfeeds 2 cells of the map
Δ -2.51-3.45 to -1.57< .0001
Placebo-adjusted changes from baseline SBP, fasting plasma glucose and body mass were -7.07 mmHg (-9.83, -4.32; p < .0001), -1.35 mmol/L (-1.83, -0.86; p < .0001) and -2.51 kg (-3.45, -1.57; p < .0001).

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

Change in glycated haemoglobin (HbA1c) from baseline to week 24bexagliflozin plus metformin (open label arm), in participants with HbA1c >10.5%describes a change within one group, not a comparison · t2dfeeds 2 cells of the map
Δ -2.82-3.23 to -2.41
The open label group change in HbA1c was -2.82% (-3.23%, -2.41%).

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.

Metformin×adverse events & safety

ContradictsOpen on the map →What to test next →

22 readable studies in this cell: 9 favour the treatment, 8 find no difference, 5 favour the comparator.

Belief with this paper
0.27contested · 4 families support, 11 contradict · against placebo
Without it
0.29This paper moves it by −0.02.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2023
Δ -0.53-0.74 to -0.32
NCT017190031,413 enrolled · 2012
Adjusted mean -0.72-0.95 to -0.48
NCT018093271,186 enrolled · 2013
Δ -0.40-0.59 to -0.21
NCT022730501,136 enrolled · 2014
Δ -8.90-13.3 to -4.50
NCT01126580807 enrolled · 2010
Δ -0.22-0.36 to -0.08
NCT01023581784 enrolled · 2009
Δ -0.67-0.96 to -0.37
NCT00386100688 enrolled · 2006
Δ 1.47-14.8 to 20.8
NCT01217073685 enrolled · 2010
Δ 1.00-9.80 to 13.1
NCT01890122647 enrolled · 2013
Δ -0.68-0.89 to -0.47
NCT00727857600 enrolled · 2007
Δ 0.860.51 to 1.22
NCT01958671461 enrolled · 2013
Δ -2.60-13.1 to 8.10
NCT00328172302 enrolled · 2006
Δ -0.85-1.10 to -0.59
NCT01485614200 enrolled · 2012
Δ 2.40-10.0 to 14.9

SGLT2 inhibitors×adverse events & safety

ContradictsOpen on the map →What to test next →

38 readable studies in this cell: 18 favour the treatment, 19 find no difference, 1 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 26 contradict · against placebo
Without it
0.00This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2023
Δ -0.53-0.74 to -0.32
NCT011374742,996 enrolled · 2010
Δ -0.46-0.59 to -0.33
NCT017190031,413 enrolled · 2012
Adjusted mean -0.33-0.56 to -0.10
NCT020991101,233 enrolled · 2014
Δ 1.40-7.40 to 10.1
NCT018093271,186 enrolled · 2013
Δ -0.46-0.66 to -0.27
NCT01649297983 enrolled · 2012
Δ -0.61-0.79 to -0.44
NCT02580591977 enrolled · 2015
Δ -0.28-0.46 to -0.11
NCT02414958730 enrolled · 2015
Δ -0.54-0.66 to -0.41
NCT01381900678 enrolled · 2011
Δ -0.51-0.64 to -0.37
NCT02033889621 enrolled · 2013
Δ 1.50-2.10 to 5.40
NCT02532855614 enrolled · 2015
Δ -2.80-10.7 to 5.10
NCT02630706506 enrolled · 2015
Δ -6.00-16.5 to 4.60
NCT02036515464 enrolled · 2014
Δ -5.70-16.5 to 5.20

SGLT2 inhibitors×glycemic control

SupportsOpen on the map →What to test next →

40 readable studies in this cell: 81 favour the treatment, 11 find no difference, 4 favour the comparator.

Belief with this paper
0.92replicated · 70 families support, 6 contradict · against placebo
Without it
0.92This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2023
Δ -1.35-1.83 to -0.86
NCT010326294,330 enrolled · 2009
Δ 2.79-1.57 to 7.15
NCT011374742,996 enrolled · 2010
Δ -0.46-0.59 to -0.33
NCT011956622,245 enrolled · 2010
Δ -0.61-0.76 to -0.46
NCT010956661,484 enrolled · 2010
Δ -0.59-0.76 to -0.42
NCT009688121,452 enrolled · 2009
Δ -0.01-0.11 to 0.09
NCT017190031,413 enrolled · 2012
Adjusted mean -0.33-0.56 to -0.10
NCT011066771,284 enrolled · 2010
Δ -0.62-0.76 to -0.48
NCT016060071,282 enrolled · 2012
Δ -0.59-0.81 to -0.37
NCT006732311,240 enrolled · 2008
Δ -0.45-0.59 to -0.31
NCT020991101,233 enrolled · 2014
Δ -0.43-0.60 to -0.27
NCT006609071,217 enrolled · 2008
Δ 0.00-0.11 to 0.11
NCT018093271,186 enrolled · 2013
Δ -0.46-0.66 to -0.27

Metformin×glycemic control

SupportsOpen on the map →What to test next →

40 readable studies in this cell: 41 favour the treatment, 13 find no difference, 7 favour the comparator.

Belief with this paper
0.84replicated · 32 families support, 6 contradict · against placebo
Without it
0.84This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2023
Δ -1.35-1.83 to -0.86
NCT017190031,413 enrolled · 2012
Adjusted mean -0.72-0.95 to -0.48
NCT018093271,186 enrolled · 2013
Δ -0.40-0.59 to -0.21
NCT022730501,136 enrolled · 2014
Δ -0.89-1.08 to -0.69
NCT008598981,093 enrolled · 2009
Δ -0.53-0.74 to -0.32
Δ -0.85-43.8 to 26.7
NCT00643851994 enrolled · 2008
Δ -0.86-1.11 to -0.62
NCT01708902876 enrolled · 2012
Δ -1.00-1.23 to -0.78
NCT00676338820 enrolled · 2008
Δ -0.05-0.26 to 0.17
NCT01126580807 enrolled · 2010
Δ -0.22-0.36 to -0.08
NCT01023581784 enrolled · 2009
Δ -0.67-0.96 to -0.37
NCT01076088744 enrolled · 2010
Δ -0.84-1.15 to -0.52
NCT00386100688 enrolled · 2006
Δ -0.49-0.67 to -0.30

Metformin×blood pressure

SupportsOpen on the map →What to test next →

6 readable studies in this cell: 2 favour the treatment, 3 find no difference, 1 favour the comparator.

Belief with this paper
0.40contested · 1 family supports, 1 contradict · against placebo
Without it
0.00This paper moves it by +0.40.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2023
Δ -7.07-9.83 to -4.32
NCT00676338820 enrolled · 2008
Δ 0.36-1.02 to 1.73

Metformin×body weight & composition

SupportsOpen on the map →What to test next →

19 readable studies in this cell: 7 favour the treatment, 6 find no difference, 6 favour the comparator.

Belief with this paper
0.50contested · 8 families support, 4 contradict · against placebo
Without it
0.50This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2023
Δ -2.51-3.45 to -1.57
NCT018093271,186 enrolled · 2013
Δ -0.90-1.60 to -0.20
NCT008598981,093 enrolled · 2009
Δ -1.37-2.03 to -0.71
NCT00643851994 enrolled · 2008
Δ -0.05-0.72 to 0.61
NCT02932475831 enrolled · 2017
Δ 0.04
NCT00676338820 enrolled · 2008
Δ -0.04-0.61 to 0.53
NCT02980276535 enrolled · 2017
Δ -0.70-1.30 to -0.20
Δ 17.05.00 to 29.0
increase 1.26-0.24 to 2.75
weight loss -16.2-60.2 to -4.40

SGLT2 inhibitors×blood pressure

SupportsOpen on the map →What to test next →

38 readable studies in this cell: 24 favour the treatment, 14 find no difference, 0 favour the comparator.

Belief with this paper
0.88established · 14 families support, 2 contradict · against placebo
Without it
0.87This paper moves it by +0.01.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2023
Δ -7.07-9.83 to -4.32
NCT010326294,330 enrolled · 2009
Δ -2.96-4.00 to -1.91
NCT011374742,996 enrolled · 2010
Δ -3.05-4.87 to -1.24
NCT011956622,245 enrolled · 2010
Δ -4.28-6.54 to -2.02
NCT011066771,284 enrolled · 2010
Δ -2.87-4.46 to -1.28
NCT020991101,233 enrolled · 2014
Δ -2.76-4.69 to -0.83
NCT018093271,186 enrolled · 2013
Δ -1.91-3.64 to -0.18
NCT02580591977 enrolled · 2015
Δ -2.10-3.90 to -0.20
NCT01042977964 enrolled · 2010
Δ -2.71-4.28 to -1.15
NCT03332771954 enrolled · 2017
Δ -4.18-6.70 to -1.65
NCT00984867833 enrolled · 2009
Δ -0.86-3.75 to 2.03
NCT03351478770 enrolled · 2017
Δ -2.05-4.87 to 0.76
NCT01137812756 enrolled · 2010
Δ -5.91-7.64 to -4.17

SGLT2 inhibitors×body weight & composition

SupportsOpen on the map →What to test next →

40 readable studies in this cell: 62 favour the treatment, 9 find no difference, 2 favour the comparator.

Belief with this paper
0.98established · 50 families support, 1 contradict · against placebo
Without it
0.98This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2023
Δ -2.51-3.45 to -1.57
NCT010326294,330 enrolled · 2009
Δ -2.96-3.47 to -2.45
NCT010956661,484 enrolled · 2010
Δ -1.10-1.65 to -0.56
NCT009688121,452 enrolled · 2009
Δ -5.20-5.70 to -4.70
NCT017190031,413 enrolled · 2012
Adjusted mean -2.50-3.33 to -1.68
NCT011066771,284 enrolled · 2010
Δ -2.40-3.00 to -1.80
NCT016060071,282 enrolled · 2012
Δ -2.05-2.73 to -1.37
NCT006732311,240 enrolled · 2008
Δ -1.00-1.50 to -0.49
NCT020991101,233 enrolled · 2014
Δ -1.85-2.48 to -1.22
NCT006609071,217 enrolled · 2008
Δ -4.65-5.14 to -4.17
NCT018093271,186 enrolled · 2013
Δ -0.90-1.60 to -0.20
NCT010956531,179 enrolled · 2010
Δ -1.37-2.01 to -0.73
NCT008598981,093 enrolled · 2009
Δ -1.97-2.64 to -1.30
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

8 citing papers in PubMed, 16 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. 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 3 institutions in 1 country.

Yuan-Di HalvorsenTranslational Medicine Group, Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.ORCID 0000-0003-2490-8024
Annie L ConeryTranslational Medicine Group, Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
John Paul LockDiabetes Center of Excellence, Department of Medicine, University of Massachusetts, Worcester, Massachusetts, USA.
Wenjiong ZhouHopkins Consulting LLC, Philadelphia, Pennsylvania, USA.
Mason W FreemanTranslational Medicine Group, Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.ORCID 0000-0002-5254-9244
Massachusetts General Hospital · USPhiladelphia Fire Department · USUniversity of Massachusetts Chan Medical School · US

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.

aimTo evaluate the relative safety and effectiveness of bexagliflozin as an adjunct to metformin for the treatment of type 2 diabetes mellitus.

methodsIn total, 317 participants were randomized to receive bexagliflozin or placebo plus metformin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24, with secondary endpoints for systolic blood pressure (SBP), fasting plasma glucose and weight loss. An open label arm enrolled participants with HbA1c >10.5% and was analysed separately.

resultsThe mean change in HbA1c was -1.09% (95% CI -1.24%, -0.94%) in the bexagliflozin arm and -0.56% (-0.71%, -0.41%) in the placebo arm, a difference of -0.53% (-0.74%, -0.32%; p < .0001). Excluding observations after rescue medication, the intergroup difference was -0.70% (-0.92, -0.48; p < .0001). The open label group change in HbA1c was -2.82% (-3.23%, -2.41%). Placebo-adjusted changes from baseline SBP, fasting plasma glucose and body mass were -7.07 mmHg (-9.83, -4.32; p < .0001), -1.35 mmol/L (-1.83, -0.86; p < .0001) and -2.51 kg (-3.45, -1.57; p < .0001). Adverse events affected 42.4% and 47.2% of subjects in the bexagliflozin and placebo arms, respectively; fewer subjects in the bexagliflozin arm experienced serious adverse events.

conclusionsBexagliflozin produced clinically meaningful improvement in glycaemic control, estimated glomerular filtration rate and SBP when added to metformin in a population of adults with diabetes.

Indexed as

Diabetes Mellitus, Type 2MetforminAdultBlood GlucoseDouble-Blind MethodDrug Therapy, CombinationGlycated HemoglobinHumansHypoglycemic AgentsPyransTreatment OutcomebexagliflozinBlood GlucoseGlycated HemoglobinHypoglycemic AgentsMetforminPyransbexagliflozinbody massFPGHbA1csafetySBPSGLT2tolerability

Identifiers

PMID37409573
OpenAlexW4383302901

What Socratic holds

Texttitle and abstract
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.