SynthesisPharmacology2010

A meta-analysis of placebo-controlled clinical trials assessing the efficacy and safety of incretin-based medications in patients with type 2 diabetes.

Walid K H Fakhoury, Corinne Lereun, Donna Wright

Registry-linked trialOpen access · bronzeAbstract readComparative StudyMeta-AnalysisSystematic Review
PubMed Publisher
In one paragraph

Synthesis in Pharmacology, 2010. The graph read 2 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. It also reports 2 associations that do not count as treatment evidence, such as RR 2.56 (1.23 to 5.33) for quality of life & behaviour. It is linked to trial NCT06894784 (Semaglutide And Empagliflozin Combination Therapy Added To Automated Insulin Delivery In Adults With Type 1 Diabetes), which is not on this map. Cited by 42 papers, 2 of them syntheses that pooled it.

2numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 2 pooled it
12.2field-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.

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

Quality of life & behaviouran association or prognostic statement, not a treatment comparison · against placebo · t2d, obesityfeeds 2 cells of the map
RR 2.561.23 to 5.33p = 0.01
The number of patient-reported hypoglycemic episodes was statistically significantly associated with the use of sitagliptin (RR = 2.56, 95% CI = 1.23-5.33, p = 0.01) and exenatide (RR = 2.40, 95% CI = 1.30-4.11, p = 0.002).
Quality of life & behaviouran association or prognostic statement, not a treatment comparison · against placebo · t2d, obesityfeeds 2 cells of the map
RR 2.401.30 to 4.11p = 0.002
The number of patient-reported hypoglycemic episodes was statistically significantly associated with the use of sitagliptin (RR = 2.56, 95% CI = 1.23-5.33, p = 0.01) and exenatide (RR = 2.40, 95% CI = 1.30-4.11, p = 0.002).

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×quality of life & behaviour

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
NCT01519674582 enrolled · 2012
Δ 0.29-1.97 to 2.56

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

GLP-1 receptor agonists×quality of life & behaviour

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

14 readable studies in this cell: 4 favour the treatment, 6 find no difference, 4 favour the comparator.

Belief with this paper
0.44contested · 4 families support, 5 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT017204463,297 enrolled · 2013
Δ 0.50-0.48 to 1.47
NCT039879191,879 enrolled · 2019
Δ -0.24-0.50 to 0.03
NCT02963935282 enrolled · 2017
Δ 0.16-1.19 to 1.52
NCT05564039282 enrolled · 2022
Δ 4.10-1.00 to 9.20
improved 2.001.52 to 5.98
NCT03951753117 enrolled · 2019
Δ -246-358 to -133
NCT04311411114 enrolled · 2020
Δ 6.63-1.53 to 14.8
NCT04019197108 enrolled · 2019
β coefficient 420-1012 to 1852
NCT0304179261 enrolled · 2017
Δ -236-322 to -149
weight loss -6.50-10.2 to -2.90

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.

NCT06894784 phase3recruitingstarted 2025, after this paper: background citation

Semaglutide And Empagliflozin Combination Therapy Added To Automated Insulin Delivery In Adults With Type 1 Diabetes (SEMPA)

Ran2025Enrolled36Registered outcomes13Posted comparisons0ConditionsDiabetes Type 1ArmsIntervention Period 1: Semaglutide + Empagliflozin, Intervention Period 2: Semaglutide + Empagliflozin Placebo, Intervention Period 3: Semaglutide Placebo + Empagliflozin, Intervention Period 4: Semaglutide Placebo + Empagliflozin Placebo
Open the trial in the graph
5 · Its place in the literature

Who cites it

42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 111 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Uncertainties around incretin-based therapies: A literature review.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2017
    Review
  14. Article
  15. Cardiovascular effects of anti-diabetes drugs.Expert opinion on drug safety · 2016
    Review
  16. Article
  17. Review
  18. Review
  19. 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

3 authors at 1 institution in 1 country.

Walid K H FakhouryIMS Health, London, UK. WFakhoury@uk.imshealth.com
Corinne Lereun
Donna Wright
Department of Health and Social Care · GB

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.

aimsA systematic review of the literature, in combination with a meta-analysis of randomized controlled trials comparing treatments with placebo, was conducted to provide an update on the clinical efficacy and safety of incretin-based medications in adult patients with type 2 diabetes.

methodsA literature search (2000-2009) identified 38 placebo-controlled trials (phase II or later - parallel design) comparing exenatide (n = 8), liraglutide (n = 7), vildagliptin (n = 11) and sitagliptin (n = 12) with placebo. Outcomes were change from baseline in HbA(1c) and in weight, and the number of patient-reported hypoglycemic episodes. HbA(1c) and weight outcomes were analyzed as weighted mean differences (WMD), and the number of hypoglycemic episodes as relative risks (RR).

resultsPatients receiving liraglutide showed greater reduction in HbA(1c) in comparison to placebo (WMD = -1.03, 95% confidence interval, CI = -1.16 to -0.90, p < 0.001) than those on sitagliptin (WMD = -0.79, 95% CI = -0.93 to -0.65, p < 0.001), exenatide (WMD = -0.75, 95% CI = -0.83 to -0.67, p < 0.001) or vildagliptin (WMD = -0.67, 95% CI = -0.83 to -0.52, p < 0.001). Weight was statistically significantly negatively associated with exenatide (WMD = -1.10, 95% CI = -1.32 to -0.87, p < 0.001) and positively associated with sitagliptin (WMD = 0.60, 95% CI = 0.33-0.87, p < 0.001) and vildagliptin (WMD = 0.56, 95% CI = 0.27-0.84, p < 0.001). The number of patient-reported hypoglycemic episodes was statistically significantly associated with the use of sitagliptin (RR = 2.56, 95% CI = 1.23-5.33, p = 0.01) and exenatide (RR = 2.40, 95% CI = 1.30-4.11, p = 0.002).

conclusionIncretin-based therapies are effective in glycemic control and also offer other advantages such as weight loss (exenatide and liraglutide). This may have an important impact on patient adherence to medication.

Indexed as

AdamantaneAdultDiabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsDrug Therapy, CombinationExenatideGlucagon-Like Peptide 1Glycated HemoglobinHumansHypoglycemiaHypoglycemic AgentsLiraglutideNitrilesPeptidesPyrazinesPyrrolidinesAdamantaneDipeptidyl-Peptidase IV InhibitorsExenatideGlucagon-Like Peptide 1Glycated HemoglobinHypoglycemic AgentsLiraglutideNitrilesPeptidesPyrazinesPyrrolidinesSitagliptin PhosphateTriazolesVenomsVildagliptin

Identifiers

PMID20616619
OpenAlexW2058468402

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

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.