Evidence mapPaperPMID 25504028Full record

SynthesisDiabetes care2015

Is there a link between liraglutide and pancreatitis? A post hoc review of pooled and patient-level data from completed liraglutide type 2 diabetes clinical trials.

Troels M Jensen, Kishore Saha, William M Steinberg

Erratum issued 17 registry-linked trialsAbstract readMeta-AnalysisReview
PubMed Publisher
In one paragraph

Synthesis in Diabetes care, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It reports registered trial NCT00154401. Cited by 23 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 2 pooled it
4.9field-weighted citation impact, top 4% 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.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · 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.

NCT00154401 phase2completed

Effect of Liraglutide on Glycaemic Control in Subjects With Type 2 Diabetes.

Ran2005Enrolled177Registered outcomes4Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2Armsliraglutide
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NCT00154414 phase2completed

Effect of Liraglutide on Glycaemic Control in Japanese Subjects With Type 2 Diabetes.

Ran2005Enrolled226Registered outcomes4Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2Armsliraglutide
PMID 18495285other papers from this trial
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NCT00294723 phase3terminated

Liraglutide Effect and Action in Diabetes (LEAD-3): Effect on Glycemic Control of Liraglutide Versus Glimepiride in Type 2 Diabetes

Ran2006Enrolled746Registered outcomes17Posted comparisons45ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsGlimepiride, liraglutide, Placebo
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NCT00318422 phase3completed

Liraglutide Effect and Action in Diabetes (LEAD-1): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Glimepiride Versus Glimepiride Monotherapy Versus Glimepiride and Rosiglitazone Combination Therapy in Subjects With Type 2 Diabetes.

Ran2006Enrolled1,041Registered outcomes5Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsGlimepiride, liraglutide, Rosiglitazone
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NCT00318461 phase3completed

Liraglutide Effect and Action in Diabetes (LEAD-2): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Metformin Versus Metformin Monotherapy Versus Metformin and Glimepiride Combination Therapy in Subjects With Type 2 Diabetes

Ran2006Enrolled1,091Registered outcomes14Posted comparisons74ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsGlimepiride, liraglutide, Metformin, Placebo
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NCT00331851 phase3completed

Liraglutide Effect and Action in Diabetes (LEAD-5): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Glimepiride and Metformin Versus Glimepiride and Metformin Combination Therapy, and Versus Insulin Glargine Added to Glimepiride and Metformin Combination Therapy in Subjects With Type 2 Diabetes.A Six-month Randomised, Double-blind, Parallel-group, Multi-centre, Multi-national Trial With an Open-label Treat-to-target Insulin Glargine Control Arm.

Ran2006Enrolled584Registered outcomes5Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsGlimepiride, Insulin glargine, liraglutide, Metformin
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NCT00333151 phase3completed

Effect on Glycemic Control of Liraglutide in Combination With Rosiglitazone Plus Metformin Versus Rosiglitazone Plus Metformin in Subjects With Type 2 Diabetes

Ran2006Enrolled576Registered outcomes4Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2Armsliraglutide, Metformin, Rosiglitazone
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NCT00395746 phase3completed

Effect of Liraglutide in Combination With Sulfonylurea (SU) on Glycaemic Control in Subjects With Type 2 Diabetes

Ran2006Enrolled264Registered outcomes13Posted comparisons30ConditionsDiabetes, Diabetes Mellitus, Type 2Armsliraglutide, Sulfonylurea
PMID 23010561PMID 20380655PMID 24843595other papers from this trial
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NCT00518882 phase3completed

Effect of Liraglutide or Exenatide Added to a Background Treatment of Metformin, Sulphonylurea or a Combination of Both on Glycaemic Control in Subjects With Type 2 Diabetes

Ran2007Enrolled467Registered outcomes55Posted comparisons85ConditionsDiabetes, Diabetes Mellitus, Type 2Armsexenatide, liraglutide
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NCT00614120 phase3completed

Effect of Liraglutide or Glimepiride Added to Metformin on Glycaemic Control in Subjects With Type 2 Diabetes

Ran2008Enrolled929Registered outcomes8Posted comparisons3ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsGlimepiride, liraglutide, Metformin, Placebo
PMID 23010561PMID 25684604PMID 21114607other papers from this trial
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NCT00620282 phase3completed

The Effect of Liraglutide on Endothelial Function in Subjects With Type 2 Diabetes Mellitus: A 12-week Randomized, Double-blind, Placebo-controlled, Parallel-group, Single-center Trial With an Open-label Glimepiride Arm

Ran2008Enrolled49Registered outcomes14Posted comparisons33ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsGlimepiride, liraglutide, Placebo
PMID 23010561PMID 25212693other papers from this trial
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NCT00700817 phase3completed

The Effect of Liraglutide Compared to Sitagliptin, Both in Combination With Metformin in Subjects With Type 2 Diabetes. A 26-week, Randomised, Open-label, Active Comparator, Three-armed, Parallel-group, Multi-centre, Multinational Trial With a 52-week Extension

Ran2008Enrolled665Registered outcomes75Posted comparisons6ConditionsDiabetes, Diabetes Mellitus, Type 2Armsliraglutide, Metformin, Sitagliptin
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NCT00856986 phase3completed

The Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes. A 26 Week, Randomised, Open-label, Parallel-group, Multicentre, Multinational Trial With a 26 Week Extension

Ran2009Enrolled987Registered outcomes32Posted comparisons3ConditionsDiabetes, Diabetes Mellitus, Type 2Armsinsulin detemir, liraglutide, Metformin
PMID 23746555PMID 22584132other papers from this trial
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NCT01508858 phase1completed

A Double-blind, Two Period Cross-over, Single Centre Trial in Healthy Subjects Investigating the Influence on the Pharmacokinetics of Ethinylestradiol and Levonorgestrel in an Oral Contraceptive Drug After Multiple Dose Administration of Liraglutide

Ran2006Enrolled21Registered outcomes7Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2Armslevonorgestrel / ethinylestradiol, liraglutide, Placebo
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NCT01509755 phase2completed

Dose-response Relationship of Five Dose Levels of NNC90-1170 and Placebo on Glycaemic Control in Type 2 Diabetic Patients Compared to OHA Treatment. A 12-week Multi-centre, Double-blind, Randomised, Parallel Group Trial With an Open Labelled OHA Arm

Ran2000Enrolled196Registered outcomes5Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsGlimepiride, liraglutide, Placebo
PMID 15161785other papers from this trial
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NCT01511172 phase2completed

Effect on Glycemic Control of Individual Maximum Effective Dose of NNC 90-1170 as Add on Therapy to Metformin Compared to Monotherapy of NNC 90-1170 or Metformin or a Metformin-SU Combination Therapy in Patients With Type 2 Diabetes. A Double-blind, Double-dummy, Randomised, Parallel-group, Dose Titration Study With an Open Labelled OHA Arm

Ran2002Enrolled145Registered outcomes11Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsGlimepiride, liraglutide, Metformin, Placebo
PMID 17039422other papers from this trial
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NCT01511198 phase2completed

NNC 90-1170 Dose-response, Efficacy and Safety: A 12-week Randomized, Multicenter, Doubleblind, Double-dummy, Parallel-group Study of Metformin and Five Doses of NNC 90-1170 in Previously-treated OHA Monotherapy Obese Subjects With Type 2 Diabetes

Ran2001Enrolled223Registered outcomes6Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2Armsliraglutide, Metformin
PMID 16026367other papers from this trial
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3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.The New England journal of medicine · 2016 · on this map
    Trial
  4. Trial
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Consensus Recommendations on GLP-1 RA Use in the Management of Type 2 Diabetes Mellitus: South Asian Task Force.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2019
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 2 countries.

Troels M JensenUK Medical Affairs, Novo Nordisk Ltd., Gatwick, U.K. toej@novonordisk.com.
Kishore SahaGlobal Safety, Novo Nordisk A/S, Bagsværd, Copenhagen, Denmark.
William M SteinbergRockville Internal Medicine Group and the Department of Medicine, George Washington University, Washington, DC.
George Washington University · USNovo Nordisk (Denmark) · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo report the incidence of pancreatitis in type 2 diabetes trials of liraglutide and details of all pancreatitis cases. RESEARCH DESIGN AND

methodsData from Novo Nordisk-sponsored trials with liraglutide (phase 2 and 3; NN2211 identifiers) completed by 19 April 2013 were pooled. All pancreatitis cases were reviewed.

resultsTotal exposure to liraglutide and active comparators was 5,021 and 1,354 patient-years, respectively (n = 6,345 and 1,846, respectively). Eight cases of acute pancreatitis (AP) with liraglutide and one with any comparator (glimepiride) were found. The incidence of AP was 1.6 cases/1,000 patient-years exposure (PYE) for liraglutide vs. 0.7 cases/1,000 PYE for total active comparators. One of the eight AP cases reported with liraglutide did not meet diagnostic criteria for AP. In six of these eight cases, recognized risk factors for AP were present and/or the onset of AP occurred >6 months after liraglutide initiation. All patients were receiving multiple medications. Four cases of chronic pancreatitis (CP) with liraglutide and none with comparators were found. One of these four cases fulfilled diagnostic criteria for CP; these criteria were not met or information was missing in the remaining three.

conclusionsBased on the small number of cases observed, the incidences of reported AP and CP were numerically greater with liraglutide than with comparators. Not all cases fulfilled diagnostic criteria, and confounding variables were present in 75% of the AP cases with liraglutide therapy, precluding firm conclusions.

Indexed as

Acute DiseaseAdultAgedDiabetes Mellitus, Type 2FemaleHumansHypoglycemic AgentsLiraglutideMaleMiddle AgedPancreatitisPancreatitis, ChronicRandomized Controlled Trials as TopicRisk FactorsSulfonylurea CompoundsglimepirideHypoglycemic AgentsLiraglutideSulfonylurea Compounds

Identifiers

PMID25504028
OpenAlexW2098737080

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

and 11 more above

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.