Evidence map›Metformin × glycemic control›PMID 25919293›Full record

ArticlePloS one2015

Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis.

Elizabeth S Mearns, Diana M Sobieraj, C Michael White, Whitney J Saulsberry, Christine G Kohn, Yunes Doleh, Eric Zaccaro, Craig I Coleman

Open access · goldFull text readComparative StudyNetwork Meta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2015. The graph read 1 number from its abstract, feeding 1 cell of the map: it . Cited by 65 papers, 8 of them syntheses that pooled it.

1number the graph read from it
1cell of the map it votes in
65citing papers in PubMed, 8 pooled it
11.8field-weighted citation impact, top 1% 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 →
-0.910 · no effect
Glycemic controlfavours the treatment · head-to-head · hypertension, obesityfeeds one cell of the map
change -0.65-0.91 to -0.39
In our network meta-analysis, the comparison of empagliflozin/linagliptin vs. dapagliflozin (change in HbA1c = -0.65, 95%CI -0.91, -0.39) would met these criteria for statistical significance and clinical superiority.
FeedsMetformin×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.

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
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

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

65 citing papers in PubMed, 8 syntheses or guidelines pooled it, 141 citations in OpenAlex.

  1. Pooled it
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  4. Pooled it
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  9. Precision and accuracy of hyperglycemic clamps in a multicenter study.American journal of physiology. Endocrinology and metabolism · 2021
    Trial
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5 more citing papers are in PubMed but not listed here.

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 3 institutions in 1 country.

Elizabeth S MearnsDepartment of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, Connecticut, United States of America; Evidence-Based Practice Center, Hartford Hospital, Hartford, Connecticut, United States of America.
Diana M SobierajDepartment of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, Connecticut, United States of America; Evidence-Based Practice Center, Hartford Hospital, Hartford, Connecticut, United States of America.
C Michael WhiteDepartment of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, Connecticut, United States of America; Evidence-Based Practice Center, Hartford Hospital, Hartford, Connecticut, United States of America.
Whitney J SaulsberryDepartment of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, Connecticut, United States of America; Evidence-Based Practice Center, Hartford Hospital, Hartford, Connecticut, United States of America.
Christine G KohnDepartment of Pharmacy Practice, School of Pharmacy, University of Saint Joseph, Hartford, Connecticut, United States of America.
Yunes DolehDepartment of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, Connecticut, United States of America.
Eric ZaccaroDepartment of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, Connecticut, United States of America.
Craig I ColemanDepartment of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, Connecticut, United States of America; Evidence-Based Practice Center, Hartford Hospital, Hartford, Connecticut, United States of America.
University of Connecticut · USHartford Hospital · USUniversity of Saint Joseph · US

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.

introductionWhen first line therapy with metformin is insufficient for patients with type 2 diabetes (T2D), the optimal adjunctive therapy is unclear. We assessed the efficacy and safety of adjunctive antidiabetic agents in patients with inadequately controlled T2D on metformin alone. MATERIALS AND

methodsA search of MEDLINE and CENTRAL, clinicaltrials.gov, regulatory websites was performed. We included randomized controlled trials of 3-12 months duration, evaluating Food and Drug Administration or European Union approved agents (noninsulin and long acting, once daily basal insulins) in patients experiencing inadequate glycemic control with metformin monotherapy (≥ 1500 mg daily or maximally tolerated dose for ≥ 4 weeks). Random-effects network meta-analyses were used to compare the weighted mean difference for changes from baseline in HbA1c, body weight (BW) and systolic blood pressure (SBP), and the risk of developing hypoglycemia, urinary (UTI) and genital tract infection (GTI).

resultsSixty-two trials evaluating 25 agents were included. All agents significantly reduced HbA1c vs. placebo; albeit not to the same extent (range, 0.43% for miglitol to 1.29% for glibenclamide). Glargine, sulfonylureas (SUs) and nateglinide were associated with increased hypoglycemia risk vs. placebo (range, 4.00-11.67). Sodium glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 analogs, miglitol and empagliflozin/linagliptin significantly reduced BW (range, 1.15-2.26 kg) whereas SUs, thiazolindinediones, glargine and alogliptin/pioglitazone caused weight gain (range, 1.19-2.44 kg). SGLT2 inhibitors, empagliflozin/linagliptin, liraglutide and sitagliptin decreased SBP (range, 1.88-5.43 mmHg). No therapy increased UTI risk vs. placebo; however, SGLT2 inhibitors were associated with an increased risk of GTI (range, 2.16-8.03).

conclusionsAdding different AHAs to metformin was associated with varying effects on HbA1c, BW, SBP, hypoglycemia, UTI and GTI which should impact clinician choice when selecting adjunctive therapy.

Indexed as

Blood PressureBody WeightDiabetes Mellitus, Type 2Drug Therapy, CombinationGlycated HemoglobinHumansHypoglycemiaHypoglycemic AgentsMetforminRandomized Controlled Trials as TopicSystoleTreatment OutcomeGlycated HemoglobinHypoglycemic AgentsMetformin

Identifiers

PMID25919293
PMCPMC4412636
OpenAlexW2059439623

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.