The DOI matches its Crossref record, with a small difference in title or year; 29 of the 29 references it cites were found in a registry or an index.
Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial
Open accessAbstract
IMPORTANCE: Weight loss of 5% to 10% can improve type 2 diabetes and related comorbidities. Few safe, effective weight-management drugs are currently available. OBJECTIVE: To investigate efficacy and safety of liraglutide vs placebo for weight management in adults with overweight or obesity and type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Fifty-six-week randomized (2:1:1), double-blind, placebo-controlled, parallel-group trial with 12-week observational off-drug follow-up period. The study was conducted at 126 sites in 9 countries between June 2011 and January 2013. Of 1361 participants assessed for eligibility, 846 were randomized. Inclusion criteria were body mass index of 27.0 or greater, age 18 years or older, taking 0 to 3 oral hypoglycemic agents (metformin, thiazolidinedione, sulfonylurea) with stable body weight, and glycated hemoglobin level 7.0% to 10.0%. INTERVENTIONS: Once-daily, subcutaneous liraglutide (3.0 mg) (n = 423), liraglutide (1.8 mg) (n = 211), or placebo (n = 212), all as adjunct to 500 kcal/d dietary deficit and increased physical activity (≥150 min/wk). MAIN OUTCOMES AND MEASURES: Three coprimary end points: relative change in weight, proportion of participants losing 5% or more, or more than 10%, of baseline weight at week 56. RESULTS: Baseline weight was 105.7 kg with liraglutide (3.0-mg dose), 105.8 kg with liraglutide (1.8-mg dose), and 106.5 kg with placebo. Weight loss was 6.0% (6.4 kg) with liraglutide (3.0-mg dose), 4.7% (5.0 kg) with liraglutide (1.8-mg dose), and 2.0% (2.2 kg) with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, -4.00% [95% CI, -5.10% to -2.90%]; liraglutide [1.8 mg] vs placebo, -2.71% [95% CI, -4.00% to -1.42%]; P < .001 for both). Weight loss of 5% or greater occurred in 54.3% with liraglutide (3.0 mg) and 40.4% with liraglutide (1.8 mg) vs 21.4% with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, 32.9% [95% CI, 24.6% to 41.2%]; for liraglutide [1.8 mg] vs placebo, 19.0% [95% CI, 9.1% to 28.8%]; P < .001 for both). Weight loss greater than 10% occurred in 25.2% with liraglutide (3.0 mg) and 15.9% with liraglutide (1.8 mg) vs 6.7% with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, 18.5% [95% CI, 12.7% to 24.4%], P < .001; for liraglutide [1.8 mg] vs placebo, 9.3% [95% CI, 2.7% to 15.8%], P = .006). More gastrointestinal disorders were reported with liraglutide (3.0 mg) vs liraglutide (1.8 mg) and placebo. No pancreatitis was reported. CONCLUSIONS AND RELEVANCE: Among overweight and obese participants with type 2 diabetes, use of subcutaneous liraglutide (3.0 mg) daily, compared with placebo, resulted in weight loss over 56 weeks. Further studies are needed to evaluate longer-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01272232.
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The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The addition of weight-loss medications has been shown to achieve significantly more weight loss than lifestyle interventions alone and produce greater A1C lowering and improvements in cardiometabolic risk factors.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [737]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“All FDAdapproved medications for chronic weight management have also been demonstrated to be effective and safe in both RCTs and a meta-analysis involving persons with T2D.735–742”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [737]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The study’s weight-loss medication arms consistently resulted in: (1) greater weight loss than lifestyle alone, (2) lower A1C values despite less need for DM medications, (3) reductions in BP, (4) lower triglycerides and higher HDL-C, (5) decreased levels of hepatic transaminases, and (6) improvements in inflammatory and other biomarkers such as CRP, fibrinogen, and adiponectin, when compared to”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [737]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“There were more episodes of gallstone disease with liraglutide, a finding that has been reported previously.”
From Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (2016) · cites this paper as [26]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“after following this regimen for 12 weeks, average weight loss stood at 4.7% of initial body mass (−5 kg as an absolute value) and increased to 6% (−6.4 kg as an absolute value) when administered doses rose from 1.8 to 3 mg respectively, compared against a mere loss of about 2.2% body mass (which equates to −2.2 kg actual value) among those on placebo.”
From Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications (2024) · cites this paper as [89]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The current study includes patients with T2D that have been shown to lose less weight with GLP1-RA therapy [29, 30, 32, 33]”
From Efficacy of the Glucagon-Like Peptide-1 Receptor Agonists Liraglutide and Semaglutide for the Treatment of Weight Regain After Bariatric surgery: a Retrospective Observational Study (2023) · cites this paper as [30]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Although most patients taking a GLP-1 RA achieve clinically meaningful weight loss, heterogeneity in response exists.3,4,5,6,7,12”
From Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity (2025) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Of the currently available agents, tirzepatide and semaglutide have the highest efficacy in terms of glucose lowering as well as weight loss, followed by dulaglutide, liraglutide, and extendedrelease exenatide (157-161).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [160]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Liraglutide 3.0 mg achieved ~ 6.0% Weight loss and 1.3% Hba1c reductions in the SCALE Diabetes trial [33].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [33]
The cited source says what the claim attributes to it.
In the citing paper
“Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) substantially lower weight,3,4,5,6,7 hemoglobin A1c levels, and cardiovascular risk,8 trials suggest they must be continued for sustained effects.9,10”
From Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity (2025) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“More than 70% of patients in clinical trials of GLP-1 RAs reported adverse events, most often gastrointestinal (GI), that were mild.3,4,5,6,7”
From Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity (2025) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Although most patients taking a GLP-1 RA achieve clinically meaningful weight loss, heterogeneity in response exists.3,4,5,6,7,12”
From Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity (2025) · cites this paper as [7]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“and has been shown to be effective in those with T2D.735–737,739”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [737]
Experimental — accuracy not yet measuredIn the citing paper
“At the end of the 56-week study period, a significant weight loss also but a decreased urinary albumin/creatinine ratio (UACR) was observed in both liraglutide arms compared with placebo (18.36, 10.79 and 2.34%, respectively).”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [43]
In the citing paper
“In both trials the difference in mean weight loss between the liraglutide and placebo-treated groups was < 5% after 1 year of treatment, but the proportion of subjects who lost ≥ 5% of baseline body weight in the liraglutide group was > 35%, from 51.8 to 54.3% [20, 21].”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [20]
In the citing paper
“While some patients with diabetes achieved ≥ 5 or 10% with placebo, higher levels of ≥ 15% in patients with diabetes were achieved almost exclusively with those who received liraglutide or semaglutide and not by those on placebo [20–22].”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [20]
In the citing paper
“In patients with diabetes, both efficacy benchmarks were achieved by semaglutide [22], while the efficacy of liraglutide did not meet the criteria in mean difference between active product vs. placebo [20, 21].”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [20]
In the citing paper
“Notably, non‐diabetic patients demonstrated greater weight loss (−8.5%) compared to diabetic patients (−4.87%), a finding consistent with previous GLP‐1 agonist studies [29, 30, 31, 32].”
From Efficacy and Safety of Orforglipron in Obese Adults With or Without Diabetes: A Systematic Review and Meta‐Analysis (2025) · cites this paper as [30]
In the citing paper
“Naltrexone plus bupropion extended-release reduces weight on average by ≈7% (≈5% placebo-subtracted) [51][52][53][54] and also more than either agent administered alone.55”
From Approach to Obesity Treatment in Primary Care: A Review (2024) · cites this paper as [55]
In the citing paper
“a 56-week intervention with liraglutide 3 mg/day as an adjunct to lifestyle modification resulted in significant weight loss compared with placebo [41, 42].”
From GLP-1 Receptor Agonists for Obesity Management in Older Adults: A Scoping Review on the Risk of Sarcopenia and Sarcopenic Obesity (2026) · cites this paper as [42]
In the citing paper
“Similar attenuation in weight loss in patients with vs without type 2 diabetes has been observed with other AOM, including orlistat,(44) naltrexone-bupropion,(45) and liraglutide 3.0 mg,(46) as well as with some behavioral interventions.(47, 48)”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [46]
In the citing paper
“In the SCALE diabetes study, a total body weight loss of 6.0% was seen in patients with T2D randomized to liraglutide (3.0 mg, daily subcutaneous injection) versus 2.0% with placebo after 56 weeks of treatment [30].”
In the citing paper
“The magnitude of weight loss observed with GLP1-RA in this real-life patient population is consistent with findings from the SCALE, SUSTAIN, and STEP clinical trials, which are based on patients without bariatric surgery.”
In the citing paper
“previous studies have shown that GLP1-RAs tend to induce less weight loss in patients with than without T2D [29, 30, 32, 33]”
In the citing paper
“Intention-to-treat 1-year placebo-subtracted weight reduction was 5.2%, 4%, 3.4%, and 6.1% for SCALE, SCALE Diabetes, SCALE IBT, and SCALE Maintenance, respectively.”
From New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics (2023) · cites this paper as [25]
In the citing paper
“Liraglutide also significantly improved treatment satisfaction vs. placebo (Diabetes Treatment Satisfaction Questionnaire) [42] (p = 0.007 for the 3 mg dose group).”
From Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects (2025) · cites this paper as [42]
In the citing paper
“The proportion of patients experiencing nausea then gradually decreased up to the end of the trial period [42,67,81,95].”
From Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects (2025) · cites this paper as [42]
In the citing paper
“In the SCALE clinical studies (liraglutide), most AEs were mild or moderate in severity, and occurred primarily within the first four to eight weeks of treatment (during dose escalation).”
From Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects (2025) · cites this paper as [42]
In the citing paper
“Based on a single study, treatment satisfaction with IBTs was high [42].”
From Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects (2025) · cites this paper as [42]
In the citing paper
“the data from SCALE trials reported similar but slightly pronounced weight loss ranging from 5.7% to 8% (31, 32, 33).”
From Effects of liraglutide on obesity-associated functional hypogonadism in men (2019) · cites this paper as [32]
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Citations
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Cited by
Sorted by citations
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, N. R., Ravn, L. S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603827 · Cited by 7,629
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Mechanisms, Pathophysiology, and Management of Obesity
Heymsfield, S. B., & Wadden, T. A. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1514009 · Cited by 1,867
GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art
Nauck, M. A., Quast, D. R., Wefers, J., & Meier, J. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101102 · Cited by 1,647
“Some data suggest that while HbA1c reduction plateaus at relatively lower doses, higher doses may still be more effective for weight loss [69,70].”
Background
Metadata
- Authors
- Davies, M. J., Bergenstal, R., Bode, B., Kushner, R. F., Lewin, A., Skjøth, T. V., Andreasen, A. H., Jensen, C. B., DeFronzo, R. A., & for the NN8022-1922 Study Group
- Affiliations
- University of Leicester (GB)
- Park Nicollet Health Services (US)
- Atlanta Diabetes Associates (US)
- Northwestern University (US)
- National Research Institute (US)
- Novo Nordisk (Denmark) (DK)
- Texas Diabetes Institute (US)
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2015-08-18
- Volume
- 314
- Issue
- 7
- Pages
- 687
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W1798757189
- Cited by
- 1,198
- References
- 29
- Citations by year
- 2026: 121 · 2025: 188 · 2024: 152 · 2023: 141 · 2022: 94 · 2021: 114 · 2020: 74 · 2019: 67 · 2018: 78 · 2017: 74 · 2016: 83 · 2015: 11
- FWCI
- 59.16
- Type
- journal article
- Language
- en
- Open access
- green
- jama.jamanetwork.com
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Leicester Research Archive (University of Leicester) (acceptedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- Leona M. and Harry B. Helmsley Charitable Trust
- MannKind Corporation
- Halozyme
- Dexcom
- Zafgen
- ResMed
- Bayer HealthCare
- Novo Nordisk
- Servier
- Bavarian Nordic
- Esperion Therapeutics
- National Institutes of Health
- Abbott Diabetes Care
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Keywords
- liraglutide, type 2 diabetes, weight loss, obesity, overweight, GLP-1 receptor agonists, physical activity, HbA1c, glycemic control, drug safety, adverse events, dose comparison, weight regain, body mass index
- MeSH terms
- Liraglutide, Adult, Aged, Body Weight, Diabetes Mellitus, Type 2, Diet, Reducing, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Injections, Subcutaneous, Male, Middle Aged, Obesity, Weight Loss, Exercise, Glucagon-Like Peptide 1
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