SynthesisBMJ open2017

Effectiveness of sitagliptin compared to sulfonylureas for type 2 diabetes mellitus inadequately controlled on metformin: a systematic review and meta-analysis.

Manuj Sharma, Nicholas Beckley, Irwin Nazareth, Irene Petersen

Open access · goldAbstract readComparative StudyMeta-AnalysisSystematic Review
In one paragraph

Synthesis in BMJ open, 2017. The graph read 3 numbers from its abstract, feeding 4 cells of the map: it finds no clear difference in 1. Cited by 13 papers, 3 of them syntheses that pooled it.

3numbers the graph read from it
2cells of the map it votes in
13citing papers in PubMed, 3 pooled it
2.7field-weighted citation impact, top 9% 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 →
1 · no effect
Blood pressureno clear difference · head-to-head · t2d, obesityfeeds 2 cells of the map
OR 0.980.85 to 1.13
Meta-analysis of three homogenous RCTs revealed a statistically significant decrease in weight with sitagliptin when compared to sulfonylureas (weighted mean difference (WMD) -2.05 kg; 95% CI -2.38 to -1.71); however, a similar change from baseline in HbA1c (WMD 0.05; 95% CI -0.03 to 0.12), fasting glucose (WMD 0.11; 95% CI -0.08 to -0.29), blood pressure, lipids and the proportion achieving HbA1c <7% by study end (OR 0.98; 95% CI 0.85 to 1.13) was observed.Non-randomised studies identified consisted of four prospective and one retrospective cohort study.

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

Glycemic controlcomparator not stated · t2d, obesityfeeds 2 cells of the map
HR 0.650.57 to 0.73
Data from two cohort studies suggested that treatment change (HR 0.65; 95% CI 0.57 to 0.73) and insulin initiation (HR 0.76; 95% CI 0.65 to 0.90) were less likely among those prescribed sitagliptin; however, inadequate reporting of HbA1c at time of treatment change made interpreting results challenging.
Glycemic controlcomparator not stated · t2d, obesityfeeds 2 cells of the map
HR 0.760.65 to 0.90
Data from two cohort studies suggested that treatment change (HR 0.65; 95% CI 0.57 to 0.73) and insulin initiation (HR 0.76; 95% CI 0.65 to 0.90) were less likely among those prescribed sitagliptin; however, inadequate reporting of HbA1c at time of treatment change made interpreting results challenging.

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×blood pressure

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

6 readable studies in this cell: 0 favour the treatment, 3 find no difference, 3 favour the comparator.

Belief with this paper
0.25no deciding trial · 0 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT011066771,284 enrolled · 2010
Δ -2.87-4.46 to -1.28
NCT00676338820 enrolled · 2008
Δ -0.05-1.60 to 1.49
NCT01137812756 enrolled · 2010
Δ -5.91-7.64 to -4.17
NCT01059825375 enrolled · 2010
Δ -0.54-3.33 to 2.26
NCT01106690344 enrolled · 2010
Δ -4.07-6.88 to -1.25
NCT03429543175 enrolled · 2018
Δ 0.91-2.40 to 4.22

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

Sulfonylureas & glinides×blood pressure

InconclusiveOpen on the map →What to test next →

5 readable studies in this cell: 0 favour the treatment, 1 find no difference, 4 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 3 contradict · head-to-head
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT03332771954 enrolled · 2017
Δ -4.18-6.70 to -1.65
NCT02033889621 enrolled · 2013
Δ -4.50-6.81 to -2.19
NCT02419612444 enrolled · 2015
Δ -3.60-6.30 to -1.00
NCT00770653305 enrolled · 2007
Δ -2.49-5.40 to 0.42
NCT02564926125 enrolled · 2016
Δ -6.81-11.0 to -2.64

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

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.

Insulin×glycemic control

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

40 readable studies in this cell: 14 favour the treatment, 14 find no difference, 13 favour the comparator.

Belief with this paper
0.50contested · 9 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT036893742,274 enrolled · 2018
Δ -0.29-0.38 to -0.20
NCT037306622,002 enrolled · 2018
Δ -0.99-1.13 to -0.86
NCT013360231,663 enrolled · 2011
Treatment contrast -0.64-0.75 to -0.53
NCT038829701,444 enrolled · 2019
Δ -0.86-1.00 to -0.72
NCT045379231,428 enrolled · 2020
Δ -1.10-1.24 to -0.97
NCT032680051,264 enrolled · 2017
Δ -0.04-0.11 to 0.03
NCT020581471,170 enrolled · 2014
Δ -0.78-0.90 to -0.67
NCT021289321,089 enrolled · 2014
Δ -0.81-0.96 to -0.67
NCT009606611,036 enrolled · 2009
Δ -0.04-0.18 to 0.11
NCT00856986987 enrolled · 2009
Δ -0.52-0.68 to -0.36
NCT01117350978 enrolled · 2010
Δ 2.54-3.88 to 8.93
NCT03214380933 enrolled · 2017
Δ 0.06-0.05 to 0.16

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

13 citing papers in PubMed, 3 syntheses or guidelines pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Observational
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. 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

4 authors at 2 institutions in 2 countries.

Manuj SharmaDepartment of Primary Care and Population Health, University College London, London, UK.ORCID http://orcid.org/0000-0002-6235-9866
Nicholas BeckleyDepartment of Primary Care and Population Health, University College London, London, UK.
Irwin NazarethDepartment of Primary Care and Population Health, University College London, London, UK.
Irene PetersenDepartment of Primary Care and Population Health, University College London, London, UK.
University College London · GBAarhus University · DK

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.

objectiveTo assess the effectiveness of sitagliptin compared to sulfonylureas as add-on to metformin in adults with type 2 diabetes mellitus from both randomised controlled trials (RCTs) and 'real-world' non-randomised studies. METHODS AND ANALYSES: We conducted a systematic review of EMBASE, MEDLINE, CENTRAL and grey literature for RCTs and non-randomised studies. We reported outcomes relating to change in HbA1c, fasting glucose, weight, blood pressure and lipids from baseline and need for treatment change. No study investigating macrovascular and microvascular diabetes complications was found. Meta-analysis was used where studies were sufficiently homogenous.

resultsSeven RCTs and five non-randomised studies were eligible for inclusion from 1335 articles retrieved. Meta-analysis of three homogenous RCTs revealed a statistically significant decrease in weight with sitagliptin when compared to sulfonylureas (weighted mean difference (WMD) -2.05 kg; 95% CI -2.38 to -1.71); however, a similar change from baseline in HbA1c (WMD 0.05; 95% CI -0.03 to 0.12), fasting glucose (WMD 0.11; 95% CI -0.08 to -0.29), blood pressure, lipids and the proportion achieving HbA1c <7% by study end (OR 0.98; 95% CI 0.85 to 1.13) was observed.Non-randomised studies identified consisted of four prospective and one retrospective cohort study. Three of these five studies were of moderate/high quality, and results though less precise suggested similar real-world comparative glycaemic and weight effectiveness for both treatments. Data from two cohort studies suggested that treatment change (HR 0.65; 95% CI 0.57 to 0.73) and insulin initiation (HR 0.76; 95% CI 0.65 to 0.90) were less likely among those prescribed sitagliptin; however, inadequate reporting of HbA1c at time of treatment change made interpreting results challenging.

conclusionSitagliptin users experienced modest weight loss compared to gain with sulfonylureas; however, this difference was around 2 kg, which may not be of major clinical significance for most individuals. Similar change was observed across most other effectiveness outcomes reported. Further studies are needed to address longer-term effectiveness outcomes for sitagliptin compared to sulfonylureas as add-on to metformin. PROSPERO REGISTRATION NUMBER: CRD42016033983.

Indexed as

AdolescentAdultAgedAged, 80 and overBlood GlucoseDiabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsFemaleGlycated HemoglobinHumansHypoglycemic AgentsInsulinMaleMetforminMiddle AgedOutcome Assessment, Health CareBlood GlucoseDipeptidyl-Peptidase IV InhibitorsGlycated HemoglobinHypoglycemic AgentsInsulinMetforminSitagliptin PhosphateSulfonylurea Compoundsmeta-analysismetforminsitagliptinsulfonylureasystematic reviewtype 2 diabetes

Identifiers

PMID29084794
PMCPMC5665259
OpenAlexW2768026039

What OpenQuestion 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 OpenQuestion graph.