Evidence map›DPP-4 inhibitors × glycemic control›PMID 29862619›Full record

Trial reportDiabetes, obesity & metabolism2018

Efficacy and safety of ipragliflozin as an add-on therapy to sitagliptin and metformin in Korean patients with inadequately controlled type 2 diabetes mellitus: A randomized controlled trial.

Kyung-Ah Han, Suk Chon, Choon Hee Chung, Soo Lim, Kwan-Woo Lee, SeiHyun Baik, Chang Hee Jung, Dong-Sun Kim, Kyong Soo Park, Kun-Ho Yoon and 5 more

Abstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2018. The graph read 5 numbers from its abstract, feeding 9 cells of the map: it supports the treatment in 6, favours the comparator in 3. Cited by 28 papers, 12 of them syntheses that pooled it.

5numbers the graph read from it
9cells of the map it votes in
28citing papers in PubMed, 12 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.

← favours the treatmentfavours the comparator →
-1.720 · no effect
Change in glycated haemoglobin (HbA1c) from baseline to end of treatment (EOT)ipragliflozin 50 mg/day as add-on therapy to metformin and sitagliptin vs placebo as add-on therapy to metformin and sitagliptinfavours the treatment · t2dfeeds 3 cells of the map
Δ -0.83-1.07 to -0.59P < .0001
The corresponding mean (SD) changes from baseline to EOT were -0.79 (0.59)% and 0.03 (0.84)%, respectively, in favour of ipragliflozin (adjusted mean difference -0.83% [95% CI -1.07 to -0.59]; P < .0001).
FeedsMetformin×adverse events & safetySGLT2 inhibitors×adverse events & safetyDPP-4 inhibitors×adverse events & safety
Homeostatic model assessment of insulin resistanceipragliflozin 50 mg/day as add-on therapy to metformin and sitagliptin vs placebo as add-on therapy to metformin and sitagliptinfavours the treatment · t2dfeeds 3 cells of the map
Δ -0.99< .05
Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference -1.64 mmol/L, -1.50 μU/mL, -1.72 kg, and -0.99, respectively; P < .05 for all).
FeedsMetformin×glycemic controlSGLT2 inhibitors×glycemic controlDPP-4 inhibitors×glycemic control
Fasting plasma glucoseipragliflozin 50 mg/day as add-on therapy to metformin and sitagliptin vs placebo as add-on therapy to metformin and sitagliptinfavours the treatment · t2dfeeds 3 cells of the map
Δ -1.64< .05
Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference -1.64 mmol/L, -1.50 μU/mL, -1.72 kg, and -0.99, respectively; P < .05 for all).
FeedsMetformin×glycemic controlSGLT2 inhibitors×glycemic controlDPP-4 inhibitors×glycemic control
Body weightipragliflozin 50 mg/day as add-on therapy to metformin and sitagliptin vs placebo as add-on therapy to metformin and sitagliptinfavours the treatment · t2dfeeds 3 cells of the map
Δ -1.72< .05
Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference -1.64 mmol/L, -1.50 μU/mL, -1.72 kg, and -0.99, respectively; P < .05 for all).
FeedsMetformin×body weight & compositionSGLT2 inhibitors×body weight & compositionDPP-4 inhibitors×body weight & composition

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

Fasting serum insulinipragliflozin 50 mg/day as add-on therapy to metformin and sitagliptin vs placebo as add-on therapy to metformin and sitagliptindirection of benefit for this outcome is not defined · t2dfeeds 3 cells of the map
Δ -1.50< .05
Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference -1.64 mmol/L, -1.50 μU/mL, -1.72 kg, and -0.99, respectively; P < .05 for all).
FeedsMetformin×glycemic controlSGLT2 inhibitors×glycemic controlDPP-4 inhibitors×glycemic control

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

SupportsOpen 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 it
0.82This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2018
Δ -0.99
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

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 · 2018
Δ -0.99
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
The study to understand the genetics of the acute response to metformi…PMID 25812009 · 1,033 enrolled · 2008
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

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 · 2018
Δ -0.99
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

DPP-4 inhibitors×adverse events & safety

ContradictsOpen on the map →What to test next →

34 readable studies in this cell: 12 favour the treatment, 17 find no difference, 5 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 19 contradict · against placebo
Without it
0.00This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2018
Δ -0.83-1.07 to -0.59
NCT040178321,441 enrolled · 2019
Δ -0.20-0.30 to -0.10
NCT020991101,233 enrolled · 2014
Δ -3.20-11.7 to 5.50
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 0.00-2.30 to 2.30
NCT004499301,050 enrolled · 2007
Δ -7.30-10.6 to -4.20
NCT008389031,049 enrolled · 2009
Δ -0.35-0.53 to -0.17
NCT01023581784 enrolled · 2009
Δ -0.57-0.87 to -0.27
NCT01682759751 enrolled · 2012
Δ -6.90-13.9 to 0.10
NCT02738879746 enrolled · 2016
Δ -2.10-9.10 to 5.00
NCT01217073685 enrolled · 2010
Δ 6.20-6.20 to 18.4
NCT01890122647 enrolled · 2013
Δ -0.49-0.70 to -0.28

DPP-4 inhibitors×body weight & composition

SupportsOpen on the map →What to test next →

29 readable studies in this cell: 8 favour the treatment, 8 find no difference, 13 favour the comparator.

Belief with this paper
0.50contested · 4 families support, 4 contradict · against placebo
Without it
0.43This paper moves it by +0.07.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2018
Δ -1.72
NCT026078651,864 enrolled · 2016
Δ -2.50-3.00 to -2.00
NCT011066771,284 enrolled · 2010
Δ -2.40-3.00 to -1.80
NCT007344741,202 enrolled · 2008
Δ -1.70-2.27 to -1.14
NCT007010901,035 enrolled · 2008
Δ -2.00-2.30 to -1.60
NCT00575588891 enrolled · 2007
Δ -2.20-2.70 to -1.70
NCT00676338820 enrolled · 2008
Δ -1.28-1.92 to -0.63
NCT00432276803 enrolled · 2007
Δ -0.50-1.03 to 0.04
NCT01137812756 enrolled · 2010
Δ -2.80-3.30 to -2.20
NCT01682759751 enrolled · 2012
IRR -3.70-10.6 to 3.30
NCT01438814689 enrolled · 2011
Δ 0.620.25 to 0.98
NCT02849080504 enrolled · 2016
Δ -1.90-2.60 to -1.20
NCT00642278451 enrolled · 2008
Δ 0.40-0.50 to 1.40

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 · 2018
Δ -0.83-1.07 to -0.59
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

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 · 2018
Δ -1.72
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
Effect of Metformin Added to Insulin on Glycemic Control Among Overwei…PMID 26624824 · 164 enrolled · 2013
Δ 17.05.00 to 29.0
Weight and Glucose Reduction Observed with a Combination of Nutritiona…PMID 27093610 · 53 enrolled · 2013
increase 1.26-0.24 to 2.75
A randomized, 48-week, placebo-controlled trial of intensive lifestyle…PMID 15302293 · 2004
weight loss -16.2-60.2 to -4.40
Outcomes in children of women with type 2 diabetes exposed to metformi…PMID 36746160 · 2023
Δ 0.07-0.31 to 0.45
Effects of metformin on the body composition in subjects with risk fac…PMID 15715892 · 2005
increase 16.5
Metformin for the prevention of diabetes among people with HIV and eit…PMID 37460828 · 2023
Δ -1.47-2.58 to -0.35

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 · 2018
Δ -0.83-1.07 to -0.59
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×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 · 2018
Δ -1.72
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

28 citing papers in PubMed, 12 syntheses or guidelines pooled it.

  1. Pooled it
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  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Review
  18. Article
  19. Metformin for the Treatment of Type 2 Diabetes in Asian Adults: A Systematic Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025
    Review
  20. Article
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

15 authors.

Kyung-Ah HanNowon Eulji Medical Center, Eulji University, Seoul, Korea.
Suk ChonKyung Hee University Hospital, Seoul, Korea.
Choon Hee ChungYonsei University Wonju Severance Christian Hospital, Gangwon, Korea.
Soo LimSeoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Korea.ORCID 0000-0002-4137-1671
Kwan-Woo LeeAjou University Hospital, Suwon-si, Korea.
SeiHyun BaikKorea University Guro Hospital, Seoul, Korea.
Chang Hee JungDepartment of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.ORCID 0000-0003-4043-2396
Dong-Sun KimDepartment of Endocrinology and Metabolism, Hanyang University Hospital, Seoul, Korea.
Kyong Soo ParkDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kun-Ho YoonDepartment of Endocrinology and Metabolism, Seoul St. Mary's Hospital, Catholic University Medical College, Seoul, Korea.
In-Kyu LeeDepartment of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.
Bong-Soo ChaDepartment of Internal Medicine, Yonsei University Severance Hospital, Seoul, Korea.ORCID 0000-0003-0542-2854
Taishi SakataniBiostatistics Group, Japan-Asia Data Science, Development, Astellas Pharma Inc., Tokyo, Japan.
Sumi ParkClinical Research Team, Development Department, Astellas Pharma Korea, Inc., Seoul, Korea.
Moon-Kyu LeeDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.ORCID 0000-0002-8728-7184

Funding

Astellas Pharma Korea, Inc.
8 · The paper itself

Abstract

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

aimTo evaluate the efficacy and safety of ipragliflozin vs placebo as add-on therapy to metformin and sitagliptin in Korean patients with type 2 diabetes mellitus (T2DM).

methodsThis double-blind, placebo-controlled, multi-centre, phase III study was conducted in Korea in 2015 to 2017. Patients were randomized to receive either ipragliflozin 50 mg/day or placebo once daily for 24 weeks in addition to metformin and sitagliptin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to end of treatment (EOT).

resultsIn total, 143 patients were randomized and 139 were included in efficacy analyses (ipragliflozin: 73, placebo: 66). Baseline mean (SD) HbA1c levels were 7.90 (0.69)% for ipragliflozin add-on and 7.92 (0.79)% for placebo. The corresponding mean (SD) changes from baseline to EOT were -0.79 (0.59)% and 0.03 (0.84)%, respectively, in favour of ipragliflozin (adjusted mean difference -0.83% [95% CI -1.07 to -0.59]; P < .0001). More ipragliflozin-treated patients than placebo-treated patients achieved HbA1c target levels of <7.0% (44.4% vs 12.1%) and < 6.5% (12.5% vs 1.5%) at EOT (P < .05 for both). Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference -1.64 mmol/L, -1.50 μU/mL, -1.72 kg, and -0.99, respectively; P < .05 for all). Adverse event rates were similar between groups (ipragliflozin: 51.4%; placebo: 50.0%). No previously unreported safety concerns were noted.

conclusionsIpragliflozin as add-on to metformin and sitagliptin significantly improved glycaemic variables and demonstrated a good safety profile in Korean patients with inadequately controlled T2DM.

Indexed as

AdultAgedBlood GlucoseDiabetes Mellitus, Type 2Double-Blind MethodDrug Therapy, CombinationFemaleGlucosidesGlycated HemoglobinHumansMaleMetforminMiddle AgedRepublic of KoreaSitagliptin PhosphateThiophenesBlood GlucoseGlucosidesGlycated HemoglobinipragliflozinMetforminSitagliptin PhosphateThiophenesDPP-4 inhibitoripragliflozinKoreanrandomized controlled trialSGLT2 inhibitortype 2 diabetes mellitus

Identifiers

PMID29862619
PMCPMC6175352

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
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.