Trial reportDiabetes care2009
Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD).
Trial report in Diabetes care, 2009. 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. An erratum has been issued. It reports registered trial NCT00333151. Cited by 292 papers, 23 of them syntheses that pooled 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
Systolic blood pressure decreased by 6.7, 5.6, and 1.1 mmHg with 1.2 and 1.8 mg liraglutide and placebo, respectively.
RESULTS: Mean A1C values decreased significantly more in the liraglutide groups versus placebo (mean +/- SE -1.5 +/- 0.1% for both 1.2 and 1.8 mg liraglutide and -0.5 +/- 0.1% for placebo).
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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.
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.
GLP-1 receptor agonists×blood pressure
No readable resultOpen on the map →What to test next →10 readable studies in this cell: 4 favour the treatment, 5 find no difference, 1 favour the comparator.
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×glycemic control
No readable resultOpen on the map →What to test next →40 readable studies in this cell: 96 favour the treatment, 17 find no difference, 10 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
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.
Effect on Glycemic Control of Liraglutide in Combination With Rosiglitazone Plus Metformin Versus Rosiglitazone Plus Metformin in Subjects With Type 2 Diabetes
A Phase III, Randomized, Parallel, Double-blind, and Non-inferiority Clinical Trial to Compare Efficacy and Safety of CinnaGen-liraglutide to Innovator Liraglutide Product (Victoza®) in Patients With Type II Diabetes (T2D)
Open the trial in the graphChinese People's Liberation Army General Hospital
Who cites it
292 citing papers in PubMed, 23 syntheses or guidelines pooled it, 837 citations in OpenAlex.
- Effect of glucagon-like peptide 1 receptor agonists on systolic blood pressure in patients with obesity, with or without diabetes: A systematic review and network meta-analysis.Clinical obesity · 2025Pooled it
- Efficacy and safety of GLP-1 agonists in the treatment of T2DM: A systematic review and network meta-analysis.Scientific reports · 2025 · on this mapPooled it
- Comparative efficacy and tolerability of currently approved incretin mimetics: A systematic analysis of placebo-controlled clinical trials.Diabetes, obesity & metabolism · 2025Pooled it
- What should the doctor prescribe-formula diet or antidiabetics? Effectiveness of formula diet-based lifestyle intervention vs. pharmacological antiglycemic therapy on weight loss and HbA1c reduction in type 2 diabetes patients-a systematic review.Frontiers in endocrinology · 2025Pooled it
- Comparison of the efficacy and safety of 10 glucagon-like peptide-1 receptor agonists as add-on to metformin in patients with type 2 diabetes: a systematic review.Frontiers in endocrinology · 2023Pooled it
- American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022Guideline
- Age, sex, disease severity, and disease duration difference in placebo response: implications from a meta-analysis of diabetes mellitus.BMC medicine · 2020Pooled it
- Pooled it
- Effect of Hemoglobin A1c Reduction or Weight Reduction on Blood Pressure in Glucagon-Like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter-2 Inhibitor Treatment in Type 2 Diabetes Mellitus: A Meta-Analysis.Journal of the American Heart Association · 2020Pooled it
- Cardiovascular outcomes of liraglutide in patients with type 2 diabetes: A systematic review and meta-analysis.Medicine · 2019 · on this mapPooled it
- Effect of liraglutide on blood pressure: a meta-analysis of liraglutide randomized controlled trials.BMC endocrine disorders · 2019 · on this mapPooled it
- Pediatric Obesity-Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline.The Journal of clinical endocrinology and metabolism · 2017 · on this mapGuideline
- Efficacy and safety of liraglutide, a once-daily human glucagon-like peptide-1 receptor agonist, in African-American people with Type 2 diabetes: a meta-analysis of sub-population data from seven phase III trials.Diabetic medicine : a journal of the British Diabetic Association · 2017Pooled it
- The efficacy and safety of liraglutide added to metformin in patients with diabetes: a meta-analysis of randomized controlled trials.Scientific reports · 2016Pooled it
- The placebo response of injectable GLP-1 receptor agonists vs. oral DPP-4 inhibitors and SGLT-2 inhibitors: a systematic review and meta-analysis.British journal of clinical pharmacology · 2016Pooled it
- Impact of diabetes duration on achieved reductions in glycated haemoglobin, fasting plasma glucose and body weight with liraglutide treatment for up to 28 weeks: a meta-analysis of seven phase III trials.Diabetes, obesity & metabolism · 2016Pooled it
- Improvement in glycated haemoglobin evaluated by baseline body mass index: a meta-analysis of the liraglutide phase III clinical trial programme.Diabetes, obesity & metabolism · 2016Pooled it
- Pooled it
- Effects of glucagon-like peptide-1 receptor agonists on weight loss in patients with type 2 diabetes: a systematic review and network meta-analysis.Journal of diabetes research · 2015 · on this mapPooled it
- Pooled it
232 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
objectiveTo determine the efficacy and safety of liraglutide (a glucagon-like peptide-1 receptor agonist) when added to metformin and rosiglitazone in type 2 diabetes. RESEARCH DESIGN AND
methodsThis 26-week, double-blind, placebo-controlled, parallel-group trial randomized 533 subjects (1:1:1) to once-daily liraglutide (1.2 or 1.8 mg) or liraglutide placebo in combination with metformin (1 g twice daily) and rosiglitazone (4 mg twice daily). Subjects had type 2 diabetes, A1C 7-11% (previous oral antidiabetes drug [OAD] monotherapy >or=3 months) or 7-10% (previous OAD combination therapy >or=3 months), and BMI <or=45 kg/m(2).
resultsMean A1C values decreased significantly more in the liraglutide groups versus placebo (mean +/- SE -1.5 +/- 0.1% for both 1.2 and 1.8 mg liraglutide and -0.5 +/- 0.1% for placebo). Fasting plasma glucose decreased by 40, 44, and 8 mg/dl for 1.2 and 1.8 mg and placebo, respectively, and 90-min postprandial glucose decreased by 47, 49, and 14 mg/dl, respectively (P < 0.001 for all liraglutide groups vs. placebo). Dose-dependent weight loss occurred with 1.2 and 1.8 mg liraglutide (1.0 +/- 0.3 and 2.0 +/- 0.3 kg, respectively) (P < 0.0001) compared with weight gain with placebo (0.6 +/- 0.3 kg). Systolic blood pressure decreased by 6.7, 5.6, and 1.1 mmHg with 1.2 and 1.8 mg liraglutide and placebo, respectively. Significant increases in C-peptide and homeostasis model assessment of beta-cell function and significant decreases in the proinsulin-to-insulin ratio occurred with liraglutide versus placebo. Minor hypoglycemia occurred more frequently with liraglutide, but there was no major hypoglycemia. Gastrointestinal adverse events were more common with liraglutide, but most occurred early and were transient.
conclusionsLiraglutide combined with metformin and a thiazolidinedione is a well-tolerated combination therapy for type 2 diabetes, providing significant improvements in glycemic control.
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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.