ArticlePloS one2018

Comparison of antidiabetic drugs added to sulfonylurea monotherapy in patients with type 2 diabetes mellitus: A network meta-analysis.

Dan Qian, Tiantian Zhang, Xiangping Tan, Peiying Zheng, Zhuoru Liang, Jingmei Xie, Jie Jiang, Bing Situ

Open access · goldFull text readNetwork Meta-Analysis
In one paragraph

Article in PloS one, 2018. The graph read 6 numbers from its abstract, feeding 6 cells of the map: it finds no clear difference in 1. Cited by 10 papers, 3 of them syntheses that pooled it.

6numbers the graph read from it
6cells of the map it votes in
10citing papers in PubMed, 3 pooled it
1.1field-weighted citation impact, top 20% 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.

Ratios

← favours the treatmentfavours the comparator →
0.250.521 · no effect
Hypoglycaemiano clear difference · head-to-head · obesity, t2dfeeds one cell of the map
OR 0.580.29 to 1.18
Compared with GLP-1RA, all agents were associated with a lower risk of hypoglycemia, except Met [OR, 0.58 (95% CI: 0.29 to 1.18)] and basal insulin [OR, 0.76 (95% CI: 0.27 to 2.17)], which appeared to have no significant effects on the risk of hypoglycemia ( Table 2 and Fig 3 ).
Hypoglycaemiano clear difference · head-to-head · obesity, t2dfeeds 2 cells of the map
OR 1.160.55 to 2.44
Compared with placebo, all treatment regimens were associated with a significantly higher risk of hypoglycemia, except the combinations of SU plus sodium-glucose co-transporter-2 inhibitor (SGLT-2i) [OR, 1.35 (95% CI: 0.81 to 2.25)] or alpha-glucosidase inhibitor (AGI) [OR, 1.16 (95% CI: 0.55 to 2.44)].
Hypoglycaemiano clear difference · head-to-head · obesity, t2dfeeds 2 cells of the map
OR 1.350.81 to 2.25
Compared with placebo, all treatment regimens were associated with a significantly higher risk of hypoglycemia, except the combinations of SU plus sodium-glucose co-transporter-2 inhibitor (SGLT-2i) [OR, 1.35 (95% CI: 0.81 to 2.25)] or alpha-glucosidase inhibitor (AGI) [OR, 1.16 (95% CI: 0.55 to 2.44)].

Differences

← favours the treatmentfavours the comparator →
-4.150 · no effect
Body weight & compositionfavours the treatment · head-to-head · obesity, t2dfeeds one cell of the map
reduced -2.91-4.15 to -1.68
In comparisons of second-line agents, SGLT-2i, GLP-1RA, and AGI more significantly reduced body weight versus TZD, Met, and DPP-4i, with changes ranging from -2.91 kg (95% CI: -4.15 to -1.68) for SGLT-2i versus TZD to -1.30 kg (95% CI: -1.98 to -0.62) for AGI versus DPP-4i.
Glycemic controlfavours the treatment · head-to-head · obesity, t2dfeeds one cell of the map
Δ -0.30-0.55 to -0.05
In comparisons of other antidiabetic drugs, the significant differences ranged from a reduction of -0.30% (95% CI: -0.55 to -0.05) for basal insulin versus DPP-4i to -0.49% (95% CI: -0.64 to -0.34) for GLP-1RA versus TZD ( S12 Table ).
Glycemic controlfavours the treatment · head-to-head · obesity, t2dfeeds one cell of the map
reductions -2.77-4.14 to -1.40
Direct pairwise meta-analyses (versus placebo) showed significant reductions in FPG with all second-line agents combined with SU, ranging from -2.77 mmol/l (95% CI: -4.14 to -1.40) for TZD to -0.62 mmol/l (95% CI: -0.78 to -0.47) for DPP-4i.

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.

Other glucose-lowering×hypoglycaemia

InconclusiveOpen on the map →What to test next →

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

Belief with this paper
0.00contested · 0 families support, 1 contradict · head-to-head
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017093055,570 enrolled · 2012
Estimate -8.40-11.1 to -6.10

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

Sulfonylureas & glinides×hypoglycaemia

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

10 readable studies in this cell: 0 favour the treatment, 1 find no difference, 9 favour the comparator.

Belief with this paper
0.50one trial · 1 family supports, 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
NCT017093055,570 enrolled · 2012
Estimate -8.40-11.1 to -6.10
NCT006609071,217 enrolled · 2008
Δ -37.2-42.3 to -32.2
NCT03332771954 enrolled · 2017
Δ -15.4-19.7 to -11.1
NCT02471404939 enrolled · 2015
Δ -4.21-6.45 to -1.97
NCT00575588891 enrolled · 2007
Δ -33.2-38.1 to -28.5
NCT01682759751 enrolled · 2012
Δ -21.3-26.5 to -16.4
NCT00792935143 enrolled · 2009
Proportions -7.70-23.6 to 8.70

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

Metformin×body weight & composition

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

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

Metformin×hypoglycaemia

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

1 readable study in this cell: 0 favour the treatment, 1 find no difference, 0 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 treatmentfavours the comparator →
0 · no effect
NCT02980276535 enrolled · 2017
Δ 0.70-5.10 to 6.60

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

Other glucose-lowering×glycemic control

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

8 readable studies in this cell: 5 favour the treatment, 0 find no difference, 3 favour the comparator.

Belief with this paper
0.50contested · 3 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017093055,570 enrolled · 2012
Δ 0.190.02 to 0.36
NCT050350821,018 enrolled · 2021
Δ -0.24-0.44 to -0.04
placebo-subtracted decrease -0.44

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
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

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

10 citing papers in PubMed, 3 syntheses or guidelines pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. The Place of Sulfonylureas in the Evolving Landscape of Combination Therapy.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2020
    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

8 authors at 2 institutions in 1 country.

Dan QianDepartment of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Tiantian ZhangCollege of Pharmacy, Jinan University, Guangzhou, China.
Xiangping TanDepartment of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Peiying ZhengDepartment of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Zhuoru LiangCollege of Pharmacy, Jinan University, Guangzhou, China.
Jingmei XieCollege of Pharmacy, Jinan University, Guangzhou, China.
Jie JiangCollege of Pharmacy, Jinan University, Guangzhou, China.
Bing SituDepartment of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-1615-1191
Jinan University · CNThird Affiliated Hospital of Guangzhou Medical University · CN

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.

aimsThis study aimed to investigate the efficacy and safety of dual therapy comprising sulfonylurea (SU) plus antidiabetic drugs for the treatment of type 2 diabetes mellitus (T2DM).

methodsWe searched the PubMed, Cochrane library, and Embase databases for randomized clinical trials (≥24 weeks) published up to December 28, 2017. Subsequently, we conducted pairwise and network meta-analyses to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) of the outcomes.

resultsThe final analyses included 24 trials with a total of 10,032 patients. Compared with placebo, all treatment regimens were associated with a significantly higher risk of hypoglycemia, except the combinations of SU plus sodium-glucose co-transporter-2 inhibitor (SGLT-2i) [OR, 1.35 (95% CI: 0.81 to 2.25)] or alpha-glucosidase inhibitor (AGI) [OR, 1.16 (95% CI: 0.55 to 2.44)]. Notably, the combination of SU plus glucagon-like peptide-1 receptor agonist (GLP-1RA) was associated with the most significant increase in the risk of hypoglycemia. Furthermore, all SU-based combination regimens reduced the glycated hemoglobin (HbA1c) and fasting plasma glucose levels (FPG). However, only combinations containing SGLT-2i [MD, -1.00 kg (95% CI: -1.73 to -0.27)] and GLP-1RA [MD, -0.56 kg (95% CI: -1.10 to -0.02)] led to weight loss.

conclusionsOur findings highlight the importance of considering the risk of hypoglycemia when selecting antidiabetic drugs to be administered concomitantly with SU. Although all classes of antidiabetic drugs improved glucose control when administered in combination with SU, SGLT-2i might be the best option with respect to factors such as hypoglycemia and body weight.

Indexed as

Blood GlucoseBody WeightDiabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsDrug CombinationsFemaleGlycated HemoglobinHumansHypoglycemiaHypoglycemic AgentsMaleMetforminRandomized Controlled Trials as TopicSulfonylurea CompoundsWeight LossBlood GlucoseDipeptidyl-Peptidase IV InhibitorsDrug CombinationsGlycated HemoglobinHypoglycemic AgentsMetforminSulfonylurea Compounds

Identifiers

PMID30148851
PMCPMC6110472
OpenAlexW2889443552

What Socratic holds

Textfull text, public
LicenceCC BY
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.