Impact of Liraglutide on Amylase, Lipase, and Acute Pancreatitis in Participants With Overweight/Obesity and Normoglycemia, Prediabetes, or Type 2 Diabetes: Secondary Analyses of Pooled Data From the SCALE Clinical Development Program
Open accessAbstract
OBJECTIVE: To describe amylase/lipase activity levels and events of acute pancreatitis (AP) in the SCALE (Satiety and Clinical Adiposity—Liraglutide Evidence in individuals with and without diabetes) weight-management trials. RESEARCH DESIGN AND METHODS: Secondary analyses were performed on pooled data from four trials (N = 5,358 with BMI ≥30, or 27 to <30 kg/m2 with ≥1 comorbidity). Of these, 1,723 had normoglycemia, 2,789 had prediabetes, and 846 had type 2 diabetes. Participants were randomized to liraglutide 3.0 mg (n = 3,302), liraglutide 1.8 mg (n = 211, only type 2 diabetes), or placebo (n = 1,845). Relationships between baseline characteristics and amylase/lipase activity at baseline and during treatment were investigated. RESULTS: Over 56 weeks, liraglutide 3.0 mg versus placebo was associated with increases in mean levels of 7% (amylase) and 31% (lipase), respectively. Similar changes in amylase/lipase levels were observed with liraglutide 1.8 mg. More participants receiving liraglutide 3.0 mg versus placebo experienced amylase (9.4% vs. 5.9%) and lipase (43.5% vs. 15.1%) elevations greater than or equal to the upper limit of normal (ULN); few had elevations ≥3 × ULN for amylase (<0.1% with liraglutide 3.0 mg or placebo) or lipase (2.9% vs. 1.5%, respectively). After liraglutide discontinuation, enzymes returned to baseline levels. Thirteen participants developed AP: 12 on (n = 9, 0.3%) or after (n = 3, 0.1%) liraglutide 3.0 mg treatment and one (0.1%) with placebo. A total of 6/13 participants with AP (5/12 liraglutide; 1 placebo) had gallstone disease evident at AP onset. Amylase/lipase elevations either 1 × ULN or ≥3 × ULN before AP onset had very low positive predictive value for AP (<1%). CONCLUSIONS: Liraglutide resulted in dose-independent, reversible increases in amylase/lipase activity, unrelated to baseline characteristics, not predicting AP onset. Gallstones possibly contributed to 50% of AP cases. Data provide no basis for amylase/lipase level monitoring in liraglutide treatment except in suspected AP.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
An increase in enzyme levels was not associated with occurrence of pancreatic events in trials with liraglutide.
“An increase in enzyme levels was not associated with occurrence of pancreatic events in trials with liraglutide (67, 68).”
From Safety of Semaglutide (2021) · cites this paper as [67]
Cites
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 · see citing works
Self-citationBanks, P. A., Bollen, T. L., Dervenis, C., Gooszen, H. G., Johnson, C. D., Sarr, M. G., Tsiotos, G. G., & Vege, S. S. (2013) · Gut · doi:10.1136/gutjnl-2012-302779 · Cited by 7,187 · see citing works
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M. L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1607141 · Cited by 6,900 · see citing works
Self-citationA Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
Pi-Sunyer, X., Astrup, A., Fujioka, K., Greenway, F., Halpern, A., Krempf, M., Lau, D. C. W., le Roux, C. W., Violante Ortiz, R., Jensen, C. B., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1411892 · Cited by 2,724 · see citing works
Self-citationPyke, C., Heller, R. S., Kirk, R. K., Ørskov, C., Reedtz-Runge, S., Kaastrup, P., Hvelplund, A., Bardram, L., Calatayud, D., & Knudsen, L. B. (2014) · Endocrinology · doi:10.1210/en.2013-1934 · Cited by 876 · cited 1× · see citing works
“GLP-1 receptors are weakly expressed on the acinar cells in the human pancreas (26), and inmice, short-termGLP-1 receptor activation leads to increased acinar cell amylase secretion (27).”
on behalf of the NN8022-1923 Investigators, Wadden, T. A., Hollander, P., Klein, S., Niswender, K., Woo, V, Hale, P. M., & Aronne, L. (2013) · International Journal of Obesity · doi:10.1038/ijo.2013.120 · Cited by 842 · see citing works
Self-citationvan Can, J., Sloth, B., Jensen, C. B., Flint, A., Blaak, E. E., & Saris, W. H. M. (2014) · International Journal of Obesity · doi:10.1038/ijo.2013.162 · Cited by 537 · cited 1× · see citing works
“It lowers body weight through decreased caloric intake while stimulating insulin secretion and reducing glucagon via a glucose-dependent mechanism (13,14).”
Self-citationFaillie, J.-L., Yu, O. H., Yin, H., Hillaire-Buys, D., Barkun, A., & Azoulay, L. (2016) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2016.1531 · Cited by 134 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1
Drucker, D. J. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.001 · Cited by 2,170 · see citing works
Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity
Drucker, D. J. (2024) · Diabetes Care · doi:10.2337/dci24-0003 · Cited by 383 · see citing works
Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand?
Tak, Y. J., & Lee, S. Y. (2021) · Current Obesity Reports · doi:10.1007/s13679-020-00422-w · Cited by 343 · see citing works
Gorgojo-Martínez, J. J., Mezquita-Raya, P., Carretero-Gómez, J., Castro, A., Cebrián-Cuenca, A., de Torres-Sánchez, A., García-de-Lucas, M. D., Núñez, J., Obaya, J. C., Soler, M. J., et al. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm12010145 · Cited by 358 · see citing works
Smits, M. M., & Van Raalte, D. H. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.645563 · Cited by 332 · see citing works
Emerging role of GLP-1 agonists in obesity: A comprehensive review of randomised controlled trials
Popoviciu, M.-S., Păduraru, L., Yahya, G., Metwally, K., & Cavalu, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310449 · Cited by 280 · see citing works
Pharmacotherapy of obesity: available medications and drugs under investigation.
Pilitsi, E., Farr, O. M., Polyzos, S. A., Perakakis, N., Nolen-Doerr, E., Papathanasiou, A.-E., & Mantzoros, C. S. (2019) · Metabolism · doi:10.1016/j.metabol.2018.10.010 · Cited by 248 · see citing works
Proteomic changes upon treatment with semaglutide in individuals with obesity
Maretty, L., Gill, D., Simonsen, L., Soh, K., Zagkos, L., Galanakis, M., Sibbesen, J., Iglesias, M. T., Secher, A., Valkenborg, D., et al. (2025) · Nature Medicine · doi:10.1038/s41591-024-03355-2 · Cited by 86 · see citing works
An evaluation of liraglutide including its efficacy and safety for the treatment of obesity
Lin, C.-H., Shao, L., Zhang, Y.-M., Tu, Y.-J., Zhang, Y., Tomlinson, B., Chan, P., & Liu, Z. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1695779 · Cited by 65 · see citing works
- Authors
- Steinberg, W. M., Rosenstock, J., Wadden, T. A., Donsmark, M., Jensen, C. B., & DeVries, J. H.
- Affiliations
- George Washington University (US)
- Dallas Diabetes Research Center (US)
- University of Pennsylvania (US)
- Novo Nordisk (Denmark) (DK)
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- DeVries, J. Hans
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2017-05-04
- Volume
- 40
- Issue
- 7
- Pages
- 839-848
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2610752282
- Cited by
- 76
- References
- 8
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 13 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 9 · 2019: 10 · 2018: 7 · 2017: 3
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-07-01)
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- liraglutide, acute pancreatitis, amylase, lipase, obesity, overweight, prediabetes, type 2 diabetes, weight management, GLP-1 receptor agonists, drug safety, adverse events, enzyme elevation, drug discontinuation, comorbidities, GLP-1 receptor antagonists
- MeSH terms
- Liraglutide, Amylases, Blood Glucose, Clinical Trials as Topic, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Lipase, Male, Middle Aged, Obesity, Prediabetic State, Biomarkers, Treatment Outcome, Pancreatitis, Acute Necrotizing, Overweight
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
