Trial reportDiabetes, obesity & metabolism2022

Long-term effects of dapagliflozin plus saxagliptin versus glimepiride on a background of metformin in patients with type 2 diabetes: Results of a 104-week extension to a 52-week randomized, phase 3 study and liver fat MRI substudy.

Juan P Frías, Jill Maaske, Lisa Suchower, Lars Johansson, Paul D Hockings, Nayyar Iqbal, John P H Wilding

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2022. The graph read 1 number from its abstract, feeding 4 cells of the map, but none could be read as for or against, so it casts no vote. It reports registered trial NCT02419612. Cited by 5 papers, 2 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 2 pooled it
0.9field-weighted citation impact, top 25% 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 4 cells of the map
OR 2.101.23 to 3.42P = 0.006
At week 156, 21.4% of DAPA+SAXA+MET versus 11.7% of GLIM+MET participants achieved therapeutic glycaemic response (HbA1c <53 mmol/mol; odds ratio 2.1, 95% CI 1.23-3.42; P = 0.006).

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.

DPP-4 inhibitors×glycemic control

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

40 readable studies in this cell: 59 favour the treatment, 19 find no difference, 24 favour the comparator.

Belief with this paper
0.82replicated · 56 families support, 12 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT015282542,004 enrolled · 2012
Slope -0.02-0.05 to 0.00
NCT026078651,864 enrolled · 2016
Δ -0.50-0.60 to -0.40
NCT001216671,462 enrolled · 2005
Δ -0.73-0.92 to -0.53
NCT040178321,441 enrolled · 2019
Δ -0.20-0.30 to -0.10
NCT011066771,284 enrolled · 2010
Δ -0.62-0.76 to -0.48
NCT016060071,282 enrolled · 2012
Δ -0.27-0.48 to -0.05
NCT004827291,246 enrolled · 2007
Δ -0.60-0.78 to -0.43
NCT020991101,233 enrolled · 2014
Δ -0.46-0.63 to -0.30
NCT019301881,231 enrolled · 2013
Δ -1.06-1.21 to -0.91
NCT007344741,202 enrolled · 2008
Δ -0.71-0.87 to -0.55
NCT022730501,136 enrolled · 2014
Δ -0.21-0.41 to -0.02
NCT004499301,050 enrolled · 2007
Δ 0.140.06 to 0.21

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

Metformin×glycemic control

No readable resultOpen 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 itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
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

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

SGLT2 inhibitors×glycemic control

No readable resultOpen 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 itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
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

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

Sulfonylureas & glinides×glycemic control

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

31 readable studies in this cell: 7 favour the treatment, 13 find no difference, 11 favour the comparator.

Belief with this paper
0.83established · 5 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
This paper’s trial, registry resultNCT02419612 · 444 enrolled · 2015
Δ -0.37-0.57 to -0.18
NCT017093055,570 enrolled · 2012
Δ 0.190.02 to 0.36
NCT009688121,452 enrolled · 2009
Δ -0.01-0.11 to 0.09
NCT006609071,217 enrolled · 2008
Δ 0.00-0.11 to 0.11
NCT003184611,091 enrolled · 2006
Δ -0.02-0.19 to 0.15
NCT008389031,049 enrolled · 2009
Δ -0.27-0.45 to -0.09
Δ 0.640.33 to 0.95
NCT03332771954 enrolled · 2017
Δ 0.12-0.12 to 0.36
NCT02471404939 enrolled · 2015
Δ 0.160.03 to 0.30
NCT00614120929 enrolled · 2008
Δ -0.06-0.23 to 0.11
NCT00575588891 enrolled · 2007
Δ 0.06-0.05 to 0.16
NCT01682759751 enrolled · 2012
Δ 0.180.06 to 0.30
NCT00294723746 enrolled · 2006
Δ -0.62-0.83 to -0.42
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.

NCT02419612 phase3completed

A 52-week International, Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel Group, Phase 3bTrial With a Blinded 104-week Long -Term Extension Period to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Glimepiride in Combination With Metformin ≥1500 mg in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Therapy Alone

Ran2015Enrolled444Registered outcomes8Posted comparisons8ConditionsDiabetesArmsdapagliflozin, Glimepiride, Placebo, Saxagliptin
Open the trial in the graph
5 · Its place in the literature

Who cites it

5 citing papers in PubMed, 2 syntheses or guidelines pooled it, 9 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Trial
  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

7 authors at 5 institutions in 3 countries.

Juan P FríasNational Research Institute, Los Angeles, California, USA.ORCID 0000-0001-9486-1255
Jill MaaskeAstraZeneca, Gaithersburg, Maryland, USA.
Lisa SuchowerKelly Services, Gaithersburg, Maryland, USA.
Lars JohanssonAntaros Medical AB, BioVenture Hub, Mölndal, Sweden.
Paul D HockingsAntaros Medical AB, BioVenture Hub, Mölndal, Sweden.
Nayyar IqbalAstraZeneca, Gaithersburg, Maryland, USA.
John P H WildingObesity and Endocrinology Research Group, Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.ORCID 0000-0003-2839-8404
Antaros Medical (Sweden) · SEAstraZeneca (United States) · USKelly Services (United States) · USNational Research Institute · USUniversity of Liverpool · GB

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 report the results of a 104-week extension to a 52-week study in which dapagliflozin plus saxagliptin (DAPA+SAXA) improved glycaemic control, liver fat and metabolic variables compared with glimepiride (GLIM) in participants with type 2 diabetes (T2D) receiving background metformin. MATERIALS AND

methodsThis extension to a 52-week global, multicentre, parallel-group, active-controlled, double-blind study (NCT02419612) continued randomized participants (1:1) on DAPA+SAXA (10/5 mg) plus placebo, or GLIM (1-6 mg) plus placebo, once daily. Eligible participants were aged ≥18 years, had T2D (glycated haemoglobin [HbA1c] 58.5-91.3 mmol/mol [7.5%-10.5%]), and a body mass index of 20.0 to 45.0 kg/m

resultsOverall, 382 participants entered and 338 completed the 104-week extension period (MRI substudy, n = 82). The need for treatment intensification during the 156-week period was lower for DAPA+SAXA+MET (37.0%) than GLIM+MET (55.6%; hazard ratio 0.52, 95% confidence interval [CI] 0.39-0.68; P < 0.001). At week 156, 21.4% of DAPA+SAXA+MET versus 11.7% of GLIM+MET participants achieved therapeutic glycaemic response (HbA1c <53 mmol/mol; odds ratio 2.1, 95% CI 1.23-3.42; P = 0.006). DAPA+SAXA+MET led to greater adjusted mean reductions from baseline in liver fat and visceral and subcutaneous adipose tissue volumes versus GLIM+MET at week 122 (least-squares mean difference from GLIM+MET -4.89%, -0.41 L and -0.44 L, respectively; nominal P values ≤ 0.008). Safety was consistent with that of the monocomponents.

conclusionsOverall, glycaemic control, metabolic benefits and efficacy were better maintained with DAPA+SAXA+MET than with GLIM+MET in T2D.

Indexed as

Diabetes Mellitus, Type 2MetforminAdamantaneAdipose TissueAdolescentAdultBenzhydryl CompoundsDipeptidesDouble-Blind MethodDrug Therapy, CombinationGlucosidesGlycated HemoglobinHumansHypoglycemic AgentsLiverMagnetic Resonance ImagingAdamantaneBenzhydryl CompoundsdapagliflozinDipeptidesglimepirideGlucosidesGlycated HemoglobinHypoglycemic AgentsMetforminsaxagliptinSulfonylurea CompoundsdapagliflozinDPP-4 inhibitorliverphase III studysulphonylureastype 2 diabetes

Identifiers

PMID34514692
PMCPMC9293136
OpenAlexW3199448784

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.