Effects of liraglutide compared with placebo on events of acute gallbladder or biliary disease in patients with type 2 diabetes at high risk for cardiovascular events in the LEADER randomized trial.

Nauck, Michael A.; Muus Ghorbani, Marie Louise; Kreiner, Eskil; Saevereid, Hans A.; Buse, John B.; the LEADER Publication Committee on behalf of the LEADER Trial Investigators

doi:10.2337/dc19-0415

Cited by 69Diabetes Treatment and ManagementGallbladder and Bile Duct DisordersDiabetes, Cardiovascular Risks, and Lipoproteins

Effects of liraglutide compared with placebo on events of acute gallbladder or biliary disease in patients with type 2 diabetes at high risk for cardiovascular events in the LEADER randomized trial.

Nauck, Michael A., Muus Ghorbani, Marie Louise, Kreiner, Eskil, Saevereid, Hans A., Buse, John B., the LEADER Publication Committee on behalf of the LEADER Trial Investigators·2019·Diabetes Care

DOI 10.2337/dc19-0415

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Abstract

OBJECTIVE To explore gallbladder- and biliary tract–related events reported for the liraglutide and placebo groups in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial. RESEARCH DESIGN AND METHODS LEADER was an international, randomized, double-blind, controlled cardiovascular (CV) outcomes trial. Participants with type 2 diabetes at high risk for CV events (n = 9,340) were randomized 1:1 to receive either liraglutide (≤1.8 mg daily; n = 4,668) or placebo (n = 4,672), with both groups also receiving standard care (treatment period: 3.5–5 years). Acute gallstone disease was a medical event of special interest. This post hoc analysis categorized captured events of acute gallbladder or biliary disease into four groups: uncomplicated gallbladder stones, complicated gallbladder stones, cholecystitis, and biliary obstruction. Time to first event by treatment group was analyzed using Cox regression. RESULTS There was an increased risk of acute gallbladder or biliary disease with liraglutide versus placebo (n = 141 of 4,668 vs. n = 88 of 4,672 patients, respectively; hazard ratio [HR] 1.60; 95% CI 1.23, 2.09; P < 0.001). Similar trends were observed for each of the four categories of gallbladder- or biliary tract–related events. Cholecystectomy was performed more frequently in liraglutide-treated patients (HR 1.56; 95% CI 1.10, 2.20; P = 0.013) but for similar proportions of the patients who experienced gallbladder- or biliary tract–related events (57% with liraglutide vs. 59% with placebo). CONCLUSIONS Although LEADER was not specifically designed to assess acute gallbladder or biliary disease, the trial showed an increased risk of gallbladder- or biliary tract–related events with liraglutide versus placebo, which appeared to be consistent across four categories of these events. Further studies should investigate the relevant mechanisms.

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Post hoc analysis of LEADER data revealed a persistent increase in the overall risk of biliary tract-related events and gallbladder diseases across four categories.
“Post hoc analysis of LEADER data revealed a persistent increase in the overall risk of biliary tract-related events and gallbladder diseases, consistently observed across four categories: uncomplicated gallbladder stones, complicated gallbladder stones, cholecystitis with/without gallbladder stones, and biliary obstruction [34].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [34]
Initially the gallbladder events were attributed to GLP-1RA-induced weight loss, as in the SCALE and LEADER trials, the patients with gallbladder events had more than average weight loss.
“Initially the gallbladder events were attributed to GLP-1RA-induced weight loss, as for example in the SCALE and LEADER trials, the patients with gallbladder events had more than average weight loss”
From Safety of Semaglutide (2021) · cites this paper as [88]

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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
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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
Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes
Wiviott, S. D., Raz, I., Bonaca, M. P., Mosenzon, O., Kato, E. T., Cahn, A., Silverman, M. G., Zelniker, T. A., Kuder, J. F., Murphy, S. A., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812389 · Cited by 6,382 · see citing works
A 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
Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome
Pfeffer, M. A., Claggett, B., Diaz, R., Dickstein, K., Gerstein, H. C., Køber, L. V., Lawson, F. C., Ping, L., Wei, X., Lewis, E. F., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1509225 · Cited by 2,409 · see citing works
Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes
Holman, R. R., Bethel, M. A., Mentz, R. J., Thompson, V. P., Lokhnygina, Y., Buse, J. B., Chan, J. C., Choi, J., Gustavson, S. M., Iqbal, N., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1612917 · Cited by 2,162 · see citing works
Self-citation
Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): A double-blind, randomised placebo-controlled trial
Hernandez, A. F., Green, J. B., Janmohamed, S., D'Agostino, R. B., Granger, C. B., Jones, N. P., Leiter, L. A., Rosenberg, A. E., Sigmon, K. N., Somerville, M. C., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)32261-x · Cited by 1,829 · see citing works
Self-citation
Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)
Buse, J. B., Rosenstock, J., Sesti, G., Schmidt, W. E., Montanya, E., Brett, J. H., Zychma, M., & Blonde, L. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60659-0 · Cited by 1,503 · see citing works
Self-citation
Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes
Nauck, M., Frid, A., Hermansen, K., Shah, N. S., Tankova, T., Mitha, I. H., Zdravkovic, M., Düring, M., Matthews, D. R., & for the LEAD-2 Study Group (2009) · Diabetes Care · doi:10.2337/dc08-1355 · Cited by 1,129 · see citing works
Self-citation
Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial
Garber, A., Henry, R., Ratner, R., Garcia-Hernandez, P. A., Rodriguez-Pattzi, H., Olvera-Alvarez, I., Hale, P. M., Zdravkovic, M., & Bode, B. (2009) · The Lancet · doi:10.1016/s0140-6736(08)61246-5 · Cited by 1,057 · see citing works
Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials
Vilsboll, T., Christensen, M., Junker, A. E., Knop, F. K., & Gluud, L. L. (2012) · BMJ · doi:10.1136/bmj.d7771 · Cited by 970 · see citing works
3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial
le Roux, C. W., Astrup, A., Fujioka, K., Greenway, F., Lau, D. C. W., Van Gaal, L., Ortiz, R. V., Wilding, J. P. H., Skjøth, T. V., Manning, L. S., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30069-7 · Cited by 850 · see citing works
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)
Zinman, B., Gerich, J., Buse, J. B., Lewin, A., Schwartz, S., Raskin, P., Hale, P. M., Zdravkovic, M., Blonde, L., & the LEAD-4 Study Investigators (2009) · Diabetes Care · doi:10.2337/dc08-2124 · Cited by 848 · see citing works
Self-citation
Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial
on behalf of the Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met+SU Study Group, Russell-Jones, D., Vaag, A., Schmitz, O., Sethi, B. K., Lalic, N., Antic, S., Zdravkovic, M., Ravn, G. M., & Simó, R. (2009) · Diabetologia · doi:10.1007/s00125-009-1472-y · Cited by 835 · see citing works
Adjust for multiple comparisons? It’s not that simple
Althouse, A. D. (2016) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2015.11.024 · Cited by 825 · see citing works
Liraglutide, a once‐daily human GLP‐1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD‐1 SU)
Marre, M., Shaw, J. E., Brändle, M., Bebakar, W. M. W., Kamaruddin, N. A., Strand, J., Zdravkovic, M. D., Thi, T. D. L., Colagiuri, S., & on behalf of the LEAD‐1 SU study group (2009) · Diabetic Medicine · doi:10.1111/j.1464-5491.2009.02666.x · Cited by 814 · see citing works
Acute Pancreatitis
Steinberg, W. M., & Tenner, S. M. (1994) · New England Journal of Medicine · doi:10.1056/nejm199404283301706 · Cited by 758 · see citing works
Increased Risk of Acute Pancreatitis and Biliary Disease Observed in Patients With Type 2 Diabetes
Noel, R. A., Braun, D. K., Patterson, R. E., & Bloomgren, G. (2009) · Diabetes Care · doi:10.2337/dc08-1755 · Cited by 434 · see citing works
An update on the pathogenesis of cholesterol gallstone disease
Ciaula, A. D., Wang, D. Q. ‐., & Portincasa, P. (2017) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000423 · Cited by 292 · see citing works
One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial
Pratley, R. E., Nauck, M. A., Bailey, T. S., Montanya, E., Cuddihy, R. M., Filetti, S., Garber, A. J., Thomsen, A. B., Hartvig, H. B., Davies, M. J., et al. (2011) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2011.02656.x · Cited by 253 · see citing works
Self-citation
Design of the liraglutide effect and action in diabetes: Evaluation of cardiovascular outcome results (LEADER) trial
Marso, S. P., Poulter, N. R., Nissen, S. E., Nauck, M. A., Zinman, B., Daniels, G. H., Pocock, S., Steinberg, W. M., Bergenstal, R. M., Mann, J. F. E., et al. (2013) · American Heart Journal · doi:10.1016/j.ahj.2013.07.012 · Cited by 244 · see citing works
Self-citation
Safety issues with glucagon‐like peptide‐1 receptor agonists (pancreatitis, pancreatic cancer and cholelithiasis): <scp>D</scp> ata from randomized controlled trials
Monami, M., Nreu, B., Scatena, A., Cresci, B., Andreozzi, F., Sesti, G., & Mannucci, E. (2017) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12926 · Cited by 243 · see citing works
Gallstones in obesity and weight loss
Erlinger, S. (2000) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-200012120-00015 · Cited by 215 · see citing works
Association of bile duct and gallbladder diseases with the use of incretin-based drugs in patients with type 2 diabetes mellitus.
Faillie, 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
Gallstones
Njeze, G. (2013) · Nigerian Journal of Surgery · doi:10.4103/1117-6806.119236 · Cited by 100 · see citing works
Amylase, Lipase, and Acute Pancreatitis in People With Type 2 Diabetes Treated With Liraglutide: Results From the LEADER Randomized Trial
Steinberg, W. M., Buse, J. B., Ghorbani, M. L. M., Ørsted, D. D., Nauck, M. A., the LEADER Steering Committee, & on behalf of the LEADER Trial Investigators (2017) · Diabetes Care · doi:10.2337/dc16-2747 · Cited by 87 · see citing works
Self-citation
Cholecystokinin secretion is suppressed by glucagon-like peptide-1: clue to the mechanism of the adverse gallbladder events of GLP-1-derived drugs
Rehfeld, J. F., Knop, F. K., Asmar, A., Madsbad, S., Holst, J. J., & Asmar, M. (2018) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.2018.1530297 · Cited by 62 · see citing works
Effect of exenatide on cholecystokinin-induced gallbladder emptying in fasting healthy subjects
Keller, J., Trautmann, M. E., Haber, H., Tham, L. S., Hunt, T., Mace, K., & Linnebjerg, H. (2012) · Regulatory Peptides · doi:10.1016/j.regpep.2012.08.005 · Cited by 61 · see citing works
GLP-1 based therapies: clinical implications for gastroenterologists
Smits, M. M., van Raalte, D. H., Tonneijck, L., Muskiet, M. H. A., Kramer, M. H. H., & Cahen, D. L. (2016) · Gut · doi:10.1136/gutjnl-2015-310572 · Cited by 61 · see citing works
Biliary effects of liraglutide and sitagliptin, a 12‐week randomized placebo‐controlled trial in type 2 diabetes patients
Smits, M. M., Tonneijck, L., Muskiet, M. H. A., Hoekstra, T., Kramer, M. H. H., Diamant, M., Nieuwdorp, M., Groen, A. K., Cahen, D. L., & van Raalte, D. H. (2016) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12748 · Cited by 56 · see citing works
New Avenues in the Regulation of Gallbladder Motility—Implications for the Use of Glucagon-Like Peptide–Derived Drugs
Gether, I. M., Nexøe-Larsen, C., & Knop, F. K. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01008 · Cited by 56 · see citing works
Effects of liraglutide on gallbladder emptying: A randomized, placebo‐controlled trial in adults with overweight or obesity
Nexøe‐Larsen, C. C., Sørensen, P. H., Hausner, H., Agersnap, M., Baekdal, M., Brønden, A., Gustafsson, L. N., Sonne, D. P., Vedtofte, L., Vilsbøll, T., et al. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13420 · Cited by 51 · see citing works
The once‐daily human GLP‐1 analogue liraglutide impacts appetite and energy intake in patients with type 2 diabetes after short‐term treatment
Flint, A., Kapitza, C., & Zdravkovic, M. (2013) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12108 · Cited by 42 · see citing works
Long-term management of type 2 diabetes with glucagon-like peptide-1 receptor agonists
Courtney, H., Nayar, R., Rajeswaran, C., & Jandhyala, R. (2017) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s126763 · Cited by 35 · see citing works
Prevalence of gallstone disease in patients with type 2 diabetes and the risk factors in North Indian population: A case control study
Sodhi, J. S., Zargar, S. A., Khateeb, S., Showkat, A., Javid, G., Laway, B. A., Parveen, S., Khan, B. A., Yattoo, G. N., Shah, A., et al. (2014) · Indian Journal of Gastroenterology · doi:10.1007/s12664-014-0502-y · Cited by 30 · see citing works
Incretin-based therapy and acute cholecystitis: a review of case reports and EudraVigilance spontaneous adverse drug reaction reporting database
Pizzimenti, V., Giandalia, A., Cucinotta, D., Russo, G. T., Smits, M., Cutroneo, P. M., & Trifirò, G. (2016) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.12373 · Cited by 30 · see citing works
Follow the LEADER—Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results Trial
Kalra, S. (2016) · Diabetes Therapy · doi:10.1007/s13300-016-0197-4 · Cited by 27 · see citing works
Ultrasound prevalence of gallstone disease in diabetic patients at Ibadan, Nigeria
Agunloye, A., Adebakin, A., Adeleye, J. O., & Ogunseyinde, A. O. (2013) · Nigerian Journal of Clinical Practice · doi:10.4103/1119-3077.106770 · Cited by 22 · see citing works
Effect of Albiglutide on Cholecystokinin‐Induced Gallbladder Emptying in Healthy Individuals: A Randomized Crossover Study
Shaddinger, B. C., Young, M. A., Billiard, J., Collins, D. A., Hussaini, A., & Nino, A. (2017) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.940 · Cited by 22 · see citing works
[Effects of glucagon-like peptides on gallbladder motility].
Gether, I. M., Nexøe-Larsen, C., Sonne, D. P., & Knop, F. K. (2018) · PubMed · Cited by 2 · see citing works

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Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2032183 · Cited by 5,205 · see citing works
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Drucker, D. J. (2024) · Diabetes Care · doi:10.2337/dci24-0003 · Cited by 383 · see citing works
Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials
He, L., Wang, J., Ping, F., Yang, N., Huang, J., Li, Y., Xu, L., Li, W., & Zhang, H. (2022) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2022.0338 · Cited by 356 · see citing works
Safety of Semaglutide
Smits, M. M., & Van Raalte, D. H. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.645563 · Cited by 332 · see citing works
Semaglutide for the treatment of overweight and obesity: A review
Bergmann, N. C., Davies, M. J., Lingvay, I., & Knop, F. K. (2023) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14863 · Cited by 265 · see citing works
Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review
Honigberg, M. C., Chang, L.-S., McGuire, D. K., Plutzky, J., Aroda, V. R., & Vaduganathan, M. (2020) · JAMA Cardiology · doi:10.1001/jamacardio.2020.1966 · Cited by 127 · see citing works
Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning
Kim, J. A., & Yoo, H. J. (2025) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2025.0242 · Cited by 71 · see citing works
“…revealed a persistent increase in the overall risk of biliary tract-related events and gallbladder diseases, consistently observed across four categories: uncomplicated gallbladder stones, complicated gallbladder stones, cholecystitis with/without gallbladder stones, and biliary obstruction [34].”
Efficacy of dulaglutide on vascular health indexes in subjects with type 2 diabetes: a randomized trial
Tuttolomondo, A., Cirrincione, A., Casuccio, A., Cuore, A. D., Daidone, M., Chiara, T. D., Raimondo, D. D., Corte, V. D., Maida, C. D., Simonetta, I., et al. (2021) · Cardiovascular Diabetology · doi:10.1186/s12933-020-01183-5 · Cited by 70 · see citing works
Decision Algorithm for Prescribing SGLT2 Inhibitors and GLP-1 Receptor Agonists for Diabetic Kidney Disease
Li, J., Albajrami, O., Zhuo, M., Hawley, C. E., & Paik, J. M. (2020) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.02690320 · Cited by 61 · see citing works
Efficacy and safety of semaglutide for weight management: evidence from the STEP program
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Side Effects Associated with Liraglutide Treatment for Obesity as Well as Diabetes
Seo, Y. (2020) · Journal of Obesity & Metabolic Syndrome · doi:10.7570/jomes20059 · Cited by 57 · see citing works
Modern Management of Cardiometabolic Continuum: From Overweight/Obesity to Prediabetes/Type 2 Diabetes Mellitus. Recommendations from the Eastern and Southern Europe Diabetes and Obesity Expert Group
Janež, A., Muzurović, E. M., Bogdański, P., Czupryniak, L., Fábryová, Ľ., Fras, Z., Guja, C., Haluzı́k, M., Kempler, P., Lalic, N. M., et al. (2024) · Diabetes Therapy · doi:10.1007/s13300-024-01615-5 · Cited by 53 · see citing works
2022 update to the position statement by Primary Care Diabetes Europe: a disease state approach to the pharmacological management of type 2 diabetes in primary care
Seidu, S., Cos, X., Brunton, S., Harris, S. B., Jansson, S. P. O., Mata‐Cases, M., Neijens, A. M. J., Topsever, P., & Khunti, K. (2022) · Primary care diabetes · doi:10.1016/j.pcd.2022.02.002 · Cited by 54 · see citing works
Global, regional, and national burden of gallbladder and biliary diseases from 1990 to 2019
Li, Z.-Z., Guan, L., Ouyang, R., Chen, Z., Ouyang, G., & Jiang, H. (2023) · World Journal of Gastrointestinal Surgery · doi:10.4240/wjgs.v15.i11.2564 · Cited by 45 · see citing works
A disease state approach to the pharmacological management of Type 2 diabetes in primary care: A position statement by Primary Care Diabetes Europe
Seidu, S., Cos, X., Brunton, S., Harris, S. B., Jansson, S. P. O., Mata‐Cases, M., Neijens, A. M. J., Topsever, P., & Khunti, K. (2020) · Primary care diabetes · doi:10.1016/j.pcd.2020.05.004 · Cited by 45 · see citing works
The role of glucagon‐like peptide‐1 receptor agonists in metabolic dysfunction‐associated steatohepatitis
Abdelmalek, M. F., Harrison, S. A., & Sanyal, A. J. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15524 · Cited by 43 · see citing works
Dipeptidyl peptidase-4 inhibitors and gallbladder or biliary disease in type 2 diabetes: systematic review and pairwise and network meta-analysis of randomised controlled trials
He, L., Wang, J., Ping, F., Yang, N., Huang, J., Li, W., Xu, L., Zhang, H., & Li, Y. (2022) · BMJ · doi:10.1136/bmj-2021-068882 · Cited by 42 · see citing works
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Zhang, Z., Du, Z., Liu, Q., Wu, T., Tang, Q., Zhang, J., Huang, C., Huang, Y., Li, R., Li, Y., et al. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154728 · Cited by 19 · see citing works
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Borderie, G., Schnebelen, M., & Baynat, L. (2021) · New England Journal of Medicine · doi:10.1056/nejmc2115776 · Cited by 6 · see citing works
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Wang, Z.-Q., Zhang, J., Tang, X., & Zhou, J. (2024) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2024.111882 · Cited by 5 · see citing works
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Xu, Z., Liu, Z., Wang, Y., Xue, J., Chang, T., Cui, Y., Cheng, Y., Liu, G., Wang, W., Zhou, Y., et al. (2023) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2023.2188192 · Cited by 1 · see citing works
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Aldhafiri, A. J. (2023) · Journal of advanced Biomedical and Pharmaceutical Sciences · doi:10.21608/jabps.2023.225432.1194 · Cited by 1 · see citing works
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Additional file 3 of Association of the gallbladder or biliary diseases with dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes: a meta-analysis of randomized controlled trials
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Additional file 5 of Association of the gallbladder or biliary diseases with dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes: a meta-analysis of randomized controlled trials
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Additional file 1 of Association of the gallbladder or biliary diseases with dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes: a meta-analysis of randomized controlled trials
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Additional file 4 of Association of the gallbladder or biliary diseases with dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes: a meta-analysis of randomized controlled trials
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Comment on Nauck et al. Effects of Liraglutide Compared With Placebo on Events of Acute Gallbladder or Biliary Disease in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events in the LEADER Randomized Trial. Diabetes Care 2019;42:1912–1920
Skelin, M., Rahelić, D., Skelin, P., & Lucijanić, M. (2020) · Diabetes Care · doi:10.2337/dc19-2039
Effects of liraglutide compared with placebo on events of acute gallbladder or biliary disease in patients with type 2 diabetes at high risk for cardiovascular events in the LEADER randomized trial. Diabetes Care 2019;42:1912-1920
Nauck, M. A., Saevereid, H. A., Kreiner, E., Rasmussen, S., & Buse, J. B. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/hmrw-yb89
Self-citation
Response to Comment on Nauck et al. Effects of Liraglutide Compared With Placebo on Events of Acute Gallbladder or Biliary Disease in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events in the LEADER Randomized Trial. Diabetes Care 2019;42:1912–1920
Nauck, M. A., KREINER, E. B., Rasmussen, S., Saevereid, H. A., & Buse, J. B. (2020) · Diabetes Care · doi:10.2337/dci19-0067 · Cited by 3 · see citing works
Self-citation
Gallstone Disease in Patients Treated with Liraglutide
Brett, A. S. (2019) · Journal watch · doi:10.1056/nejm-jw.na50110
Amylase, lipase, and acute pancreatitis in people with type 2 diabetes treatedwith liraglutide: Results from the LEADER randomized trial
Wm, S., Ørsted, D. D., Nauck, M. A., Buse, J. B., on behalf of the LEADER Trial Investigators The LEADER Steering Committee, & Ghorbani, M. L. M. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/w55w-c869
Self-citation

Authors: Nauck, M. A., Muus Ghorbani, M. L., Kreiner, E., Saevereid, H. A., Buse, J. B., & the LEADER Publication Committee on behalf of the LEADER Trial Investigators
Affiliations: St. Josef-Hospital (DE)
Novo Nordisk A/S, Søborg, Denmark
Novo Nordisk (Denmark) (DK)
University of North Carolina at Chapel Hill (US)
Corresponding author: Nauck, Michael A.
ORCID: Nauck, Michael A.
Buse, John B.
Venue: Diabetes Care
Publisher: American Diabetes Association
Published: 2019-08-09
Volume: 42
Issue: 10
Pages: 1912-1920
ISSN: 0149-5992 (ISSN-L)
1935-5548
DOI: 10.2337/dc19-0415
OpenAlex: W2969051643
Cited by: 69
References: 41
Citations by year: 2026: 9 · 2025: 8 · 2024: 9 · 2023: 6 · 2022: 18 · 2021: 7 · 2020: 9 · 2019: 3
FWCI: 7.51
Type: journal article
Language: en
Open access: closed
Licence: www.diabetesjournals.org/content/license (vor, 42 d)
Locations: Diabetes Care (publishedVersion)
PubMed (publishedVersion)
Funders: Novo Nordisk
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gallbladder and Bile Duct Disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: liraglutide, biliary tract diseases, gallstones, cholecystitis, biliary obstruction, cholecystectomy, type 2 diabetes, GLP-1 receptor agonists, cardiovascular risk, adverse events
MeSH terms: Liraglutide, Acute Disease, Aged, Cardiovascular Diseases, Cholecystitis, Cholestasis, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Proportional Hazards Models, Treatment Outcome, Gallstones

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Effects of liraglutide compared with placebo on events of acute gallbladder or biliary disease in patients with type 2 diabetes at high risk for cardiovascular events in the LEADER randomized trial.

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