Trial reportDiabetes care2009
Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study.
Trial report in Diabetes care, 2009. The graph read 3 numbers from its abstract, feeding 2 cells of the map: it supports the treatment in 1. It reports registered trial NCT00318461. Cited by 404 papers, 25 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.
RESULTS: A1C values were significantly reduced in all liraglutide groups versus the placebo group (P < 0.0001) with mean decreases of 1.0% for 1.8 mg liraglutide, 1.2 mg liraglutide, and glimepiride and 0.7% for 0.6 mg liraglutide and an increase of 0.1% for placebo.
RESULTS: A1C values were significantly reduced in all liraglutide groups versus the placebo group (P < 0.0001) with mean decreases of 1.0% for 1.8 mg liraglutide, 1.2 mg liraglutide, and glimepiride and 0.7% for 0.6 mg liraglutide and an increase of 0.1% for placebo.
Body weight decreased in all liraglutide groups (1.8-2.8 kg) compared with an increase in the glimepiride group (1.0 kg; P < 0.0001).
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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×glycemic control
SupportsOpen on the map →What to test next →40 readable studies in this cell: 89 favour the treatment, 16 find no difference, 10 favour the comparator.
GLP-1 receptor agonists×body weight & composition
No readable resultOpen on the map →What to test next →40 readable studies in this cell: 74 favour the treatment, 15 find no difference, 10 favour the comparator.
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.
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
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 graphEfficacy and Tolerance of Liraglutide for Weight Loss in Obese Type 2 Diabetic Hemodialysis Patients
Chinese People's Liberation Army General Hospital
Interest of GLP1 Analogues (aGLP1) in Overweight Type 2 Diabetic Patients With Chronic Inflammatory Bowel Disease (IBD)
Who cites it
404 citing papers in PubMed, 25 syntheses or guidelines pooled it, 1,119 citations in OpenAlex.
- The effect of GLP-1 receptor agonists on osteoarthritis risk in individuals with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized controlled trials.Acta diabetologica · 2026Pooled it
- Reassessing cancer risk with GLP-1 receptor agonists: a comprehensive meta-analysis of gastrointestinal malignancies.Frontiers in pharmacology · 2026Pooled it
- Divergent Risks of Hematologic Malignancies Associated with GLP-1 Receptor Agonists and SGLT2 Inhibitors: Preliminary Findings from a Pilot Network Meta-Analysis.Biomolecules · 2025Pooled it
- Comparative efficacy and tolerability of currently approved incretin mimetics: A systematic analysis of placebo-controlled clinical trials.Diabetes, obesity & metabolism · 2025Pooled it
- Glucagon-Like Peptide-1 Receptor Agonists and Risk of Venous Thromboembolism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Journal of the American Heart Association · 2025Pooled it
- The pharmacodynamics-based prophylactic benefits of GLP-1 receptor agonists and SGLT2 inhibitors on neurodegenerative diseases: evidence from a network meta-analysis.BMC medicine · 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
- A Review and Meta-Analysis of the Safety and Efficacy of Using Glucagon-like Peptide-1 Receptor Agonists.Medicina (Kaunas, Lithuania) · 2024Pooled it
- Cost-Effectiveness of Newer Antidiabetic Drugs as Second-Line Treatment for Type 2 Diabetes: A Systematic Review.Advances in therapy · 2023Pooled 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
- Use of GLP-1 Receptor Agonists and Occurrence of Thyroid Disorders: a Meta-Analysis of Randomized Controlled Trials.Frontiers in endocrinology · 2022Pooled it
- 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
- Metformin and second- or third-generation sulphonylurea combination therapy for adults with type 2 diabetes mellitus.The Cochrane database of systematic reviews · 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
- Effect of Long-term Incretin-Based Therapies on Ischemic Heart Diseases in Patients with Type 2 Diabetes Mellitus: A Network Meta-analysis.Scientific reports · 2017Pooled it
- Comparisons of weight changes between sodium-glucose cotransporter 2 inhibitors treatment and glucagon-like peptide-1 analogs treatment in type 2 diabetes patients: A meta-analysis.Journal of diabetes investigation · 2017Pooled it
- How Consistent is the Relationship between Improved Glucose Control and Modelled Health Outcomes for People with Type 2 Diabetes Mellitus? a Systematic Review.PharmacoEconomics · 2017Pooled it
344 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
objectiveThe efficacy and safety of adding liraglutide (a glucagon-like peptide-1 receptor agonist) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes (OAD) therapy. RESEARCH DESIGN AND
methodsIn this 26-week, double-blind, double-dummy, placebo- and active-controlled, parallel-group trial, 1,091 subjects were randomly assigned (2:2:2:1:2) to once-daily liraglutide (either 0.6, 1.2, or 1.8 mg/day injected subcutaneously), to placebo, or to glimepiride (4 mg once daily). All treatments were in combination therapy with metformin (1g twice daily). Enrolled subjects (aged 25-79 years) had type 2 diabetes, A1C of 7-11% (previous OAD monotherapy for > or =3 months) or 7-10% (previous OAD combination therapy for > or =3 months), and BMI < or =40 kg/m(2).
resultsA1C values were significantly reduced in all liraglutide groups versus the placebo group (P < 0.0001) with mean decreases of 1.0% for 1.8 mg liraglutide, 1.2 mg liraglutide, and glimepiride and 0.7% for 0.6 mg liraglutide and an increase of 0.1% for placebo. Body weight decreased in all liraglutide groups (1.8-2.8 kg) compared with an increase in the glimepiride group (1.0 kg; P < 0.0001). The incidence of minor hypoglycemia with liraglutide ( approximately 3%) was comparable to that with placebo but less than that with glimepiride (17%; P < 0.001). Nausea was reported by 11-19% of the liraglutide-treated subjects versus 3-4% in the placebo and glimepiride groups. The incidence of nausea declined over time.
conclusionsIn subjects with type 2 diabetes, once-daily liraglutide induced similar glycemic control, reduced body weight, and lowered the occurrence of hypoglycemia compared with glimepiride, when both had background therapy of metformin.
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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.