Evidence map›DPP-4 inhibitors × adverse events & safety›PMID 35503625›Full record

SynthesisEuropean review for medical and pharmacological sciences2022

Efficacy and safety of combination therapy with vildagliptin and metformin vs. metformin monotherapy for Type 2 Diabetes Mellitus therapy: a meta-analysis.

Y Ding, Y Liu, Y Qu, M Lin, F Dong, Y Li, L Cao, S Lin

Abstract readMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in European review for medical and pharmacological sciences, 2022. The graph read 4 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 10 papers, 3 of them syntheses that pooled it.

4numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 3 pooled it
2.4field-weighted citation impact, top 10% 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

Adverse events & safetycomparator not stated · obesity, t2dfeeds 2 cells of the map
RR 0.720.58 to 0.91p=0.006
In terms of safety, the vildagliptin plus metformin as combination therapy did not increase risk of total adverse events (AEs) [RR=0.98, 95% CI (0.94,1.02), p=0.29], however there were significant statistical difference and did not increase the risk of diarrhea [RR=0.55, 95% CI (0.40, 0.76), p=0.0003] and Gastrointestinal (GI) disorders [RR=0.72, 95% CI (0.58, 0.91), p=0.006], but significantly increased risk of dizziness [RR=1.41, 95% CI (1.06, 1.88), p=0.02] when compared with metformin monotherapy.
FeedsMetformin×adverse events & safetyDPP-4 inhibitors×adverse events & safety
Adverse events & safetycomparator not stated · obesity, t2dfeeds 2 cells of the map
RR 1.411.06 to 1.88p=0.02
In terms of safety, the vildagliptin plus metformin as combination therapy did not increase risk of total adverse events (AEs) [RR=0.98, 95% CI (0.94,1.02), p=0.29], however there were significant statistical difference and did not increase the risk of diarrhea [RR=0.55, 95% CI (0.40, 0.76), p=0.0003] and Gastrointestinal (GI) disorders [RR=0.72, 95% CI (0.58, 0.91), p=0.006], but significantly increased risk of dizziness [RR=1.41, 95% CI (1.06, 1.88), p=0.02] when compared with metformin monotherapy.
FeedsMetformin×adverse events & safetyDPP-4 inhibitors×adverse events & safety
Adverse events & safetycomparator not stated · obesity, t2dfeeds 2 cells of the map
RR 0.550.40 to 0.76p=0.0003
In terms of safety, the vildagliptin plus metformin as combination therapy did not increase risk of total adverse events (AEs) [RR=0.98, 95% CI (0.94,1.02), p=0.29], however there were significant statistical difference and did not increase the risk of diarrhea [RR=0.55, 95% CI (0.40, 0.76), p=0.0003] and Gastrointestinal (GI) disorders [RR=0.72, 95% CI (0.58, 0.91), p=0.006], but significantly increased risk of dizziness [RR=1.41, 95% CI (1.06, 1.88), p=0.02] when compared with metformin monotherapy.
FeedsMetformin×adverse events & safetyDPP-4 inhibitors×adverse events & safety
Adverse events & safetycomparator not stated · obesity, t2dfeeds 2 cells of the map
RR 0.980.94 to 1.02p=0.29
In terms of safety, the vildagliptin plus metformin as combination therapy did not increase risk of total adverse events (AEs) [RR=0.98, 95% CI (0.94,1.02), p=0.29], however there were significant statistical difference and did not increase the risk of diarrhea [RR=0.55, 95% CI (0.40, 0.76), p=0.0003] and Gastrointestinal (GI) disorders [RR=0.72, 95% CI (0.58, 0.91), p=0.006], but significantly increased risk of dizziness [RR=1.41, 95% CI (1.06, 1.88), p=0.02] when compared with metformin monotherapy.
FeedsMetformin×adverse events & safetyDPP-4 inhibitors×adverse events & safety

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×adverse events & safety

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

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

Metformin×adverse events & safety

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

22 readable studies in this cell: 8 favour the treatment, 8 find no difference, 6 favour the comparator.

Belief with this paper
0.27contested · 4 families support, 11 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 -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

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, 17 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. 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 1 institution in 1 country.

Y DingCollege of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. caolingyong@163.com.
Y Liu
Y Qu
M Lin
F Dong
Y Li
L Cao
S Lin
Zhejiang Chinese 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.

objectiveThe aim is to assess the comparative efficacy and safety of combination therapy with vildagliptin and metformin vs. metformin monotherapy in the treatment of type 2 diabetes mellitus (T2DM). MATERIALS AND

methodsWe searched on PubMed, Cochrane Library, Web of Science, and Embase databases for randomized controlled trials (RCTs) of combination therapy with vildagliptin and metformin vs. metformin monotherapy in patients with T2DM published up to 30 February 2021. The Cochrane tool and Revman 5.3 software was used to assess the risk of bias and conducted the meta-analysis in the included RCTs. Evidence level was assessed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.

resultsA total of 11 RCTs and 8533 patients were included. For the efficacy, we found that combination therapy with vildagliptin and metformin (dose of metformin ≥1500mg/d) had a significantly higher reduction in hemoglobin A1c (HbA1c) [mean differences (MD)= -0.59, 95% CI (-0.28, -0.16), p<0.00001] and fasting plasma glucose (FPG) level [MD= -0.82, 95% CI (-1.09, -0.56), p<0.00001] than combination therapy with vildagliptin and metformin (dose of metformin <1500 mg/d). Vildagliptin plus metformin as combination therapy reduced body weight loss ratio [MD=0.22, 95% CI (0.17, 0.27), p<0.00001] when compared with metformin monotherapy. In terms of safety, the vildagliptin plus metformin as combination therapy did not increase risk of total adverse events (AEs) [RR=0.98, 95% CI (0.94,1.02), p=0.29], however there were significant statistical difference and did not increase the risk of diarrhea [RR=0.55, 95% CI (0.40, 0.76), p=0.0003] and Gastrointestinal (GI) disorders [RR=0.72, 95% CI (0.58, 0.91), p=0.006], but significantly increased risk of dizziness [RR=1.41, 95% CI (1.06, 1.88), p=0.02] when compared with metformin monotherapy.

conclusionsCompared with metformin, vildagliptin combined with metformin could significantly reduce FPG, HbA1c and body weight. When the dose of metformin in the combination group of vildagliptin and metformin is ≥1500mg/d, the results showed significant reduction in HbA1c and FPG. In addition, it had no risk of increase in total AEs, diarrhea, and GI disorders, but had significant risk of increase in dizziness. GRADE showed that the quality of evidence had high certainty in FPG and moderate certainty in HbA1c, body weight and all AEs.

Indexed as

Diabetes Mellitus, Type 2MetforminBlood GlucoseBody WeightDiarrheaDizzinessDrug Therapy, CombinationGlycated HemoglobinHumansHypoglycemic AgentsNitrilesPyrrolidinesVildagliptinBlood GlucoseGlycated HemoglobinHypoglycemic AgentsMetforminNitrilesPyrrolidinesVildagliptin

Identifiers

PMID35503625
OpenAlexW4225412359

What OpenQuestion 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 OpenQuestion graph.