Pancreatitis and pancreatic cancer in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists: an updated meta-analysis of randomized controlled trials

Nreu, Besmir; Dicembrini, Ilaria; Tinti, Federico; Mannucci, Edoardo; Monami, Matteo

doi:10.23736/s2724-6507.20.03219-8

Cited by 9 publications

(4 citation statements)

References 65 publications

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“…They were unable to find an increased risk of pancreatic cancer over 7 years following the start of GLP-1 RAs. Furthermore, a recent meta-analysis published in Italy in July 2023 did not show an association of pancreatic cancer with GLP-1 RA use [88]. Our study adds to those recent studies' additional evidence of GLP-1 RA safety.…”

Section: Our Study and Current Evidencesupporting

confidence: 62%

The Use of Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus Does Not Increase the Risk of Pancreatic Cancer: A U.S.-Based Cohort Study

Ayoub,

Faris,

Juranovic

et al. 2024

Cancers

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Background: GLP-1 RAs are widely used for T2DM treatment due to their cardiorenal and metabolic benefits. This study examines the risk of pancreatic cancer with GLP-1 RA use in patients with T2DM. Methods: We analyzed TriNetX’s deidentified research database using the U.S. Collaborative Network comprising 62 healthcare organizations across the U.S.A. Patients with T2DM were split into two cohorts: one receiving GLP-1 RAs, and one not receiving GLP-1 RAs. We excluded patients with known risk factors for pancreatic cancer, including pancreatic cysts, a personal or family history of BRCA1, BRCA2, CDKN2A, KRAS, MEN1, MLH1, MSH2, NOTCH1, PALB2, PMS2, and PRSS1S genes, family history of pancreatic cancer, and VHL syndrome. Using a 1:1 propensity score-matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then compared the rate of pancreatic cancer between the two cohorts at a 7-year interval. Results: Out of 7,146,015 identified patients with T2DM, 10.3% were on a GLP-1 RA and 89.7% were not. Post-PSM, 721,110 patients were in each group. Patients on GLP-1 RAs had a 0.1% risk compared to a 0.2% risk of pancreatic cancer in the 7-year timeframe. Conclusion: The use of GLP-1 RAs in patients with type 2 diabetes mellitus (T2DM) does not appear to substantially elevate the risk of pancreatic cancer; in fact, it may potentially exert a protective effect.

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Section: Our Study and Current Evidencesupporting

confidence: 62%

The Use of Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus Does Not Increase the Risk of Pancreatic Cancer: A U.S.-Based Cohort Study

Ayoub,

Faris,

Juranovic

et al. 2024

Cancers

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“…More serious adverse effects are exceedingly rare but include hypoglycemia, pancreatic disease, biliary and gallbladder disease, and renal injury or failure 74,76,[81][82][83] . A 2022 systematic review reported hypoglycemic events in 0% to 8% of patients 84 .…”

Section: Adverse Effectsmentioning

confidence: 99%

Glucagon-like Peptide-1 Agonists

Chan,

Mika,

Martin

et al. 2024

JBJS Reviews

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» Orthopaedic surgeons are increasingly likely to encounter patients with obesity and/or type 2 diabetes taking glucagon-like peptide-1 (GLP-1) agonists for weight loss.» GLP-1 agonists are an effective treatment for weight loss with semaglutide and tirzepatide being the most effective agents. Randomized controlled trials using these agents have reported weight loss up to 21 kg (46 lb).» The use of GLP-1 agonists preoperatively can improve glycemic control, which can potentially reduce the risk of postoperative complications. However, multiple cases of intraoperative aspiration/regurgitation have been reported, potentially related to the effect of GLP-1 agonists on gastric emptying.» While efficacious, GLP-1 agonists may not produce sufficient weight loss to achieve body mass index cutoffs for total joint arthroplasty depending on individual patient factors, including starting bodyweight. Multifactorial approaches to weight loss with focus on lifestyle modification in addition to GLP-1 agonists should be considered in such patients.» Although GLP-1 agonists are efficacious agents for weight loss, they may not be accessible or affordable for all patients. Each patient's unique circumstances should be considered when creating an ideal weight loss plan during optimization efforts.

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“…Actually, a causal association between incretin-based drugs and AP has not been definitively confirmed and a recent meta-analysis of 43 randomized controlled trials found no clear evidence of a strict relationship between AP in people with type 2 diabetes and GLP1RAs ( 37 ).…”

Section: Introductionmentioning

confidence: 99%

Case report: GLP1RA for the treatment of diabetes in liver transplanted people. Do they increase the risk of pancreatitis?

Grancini,

Cogliati,

Gaglio

et al. 2024

Front. Endocrinol.

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The incidence of acute pancreatitis (AP) in liver transplanted people is reported to be 1.5-8%. On the other hand, the evidence for a causal relationship between glucagon-like peptide 1 receptor agonists (GLP1RAs) and pancreatitis in people with type 2 diabetes is still weak. In addition, there are currently no data on a possible increased risk of AP in liver-transplanted individuals with diabetes treated with GLP1RAs. In a population of liver-transplanted individuals with diabetes receiving GLP1RA-based therapy, we reported an incidence of AP of 3.0% (two subjects). No cases were reported in liver-transplanted individuals with diabetes receiving SGLT2 inhibitors, insulin or metformin, neither in kidney or lung-transplanted patients treated with GLP1RAs. In both patients with AP, the only additional risk factor for its development was a history of re-transplantation (liver or combined kidney/liver). For this reason, we suggest particular caution when considering GLP1RAs-based therapies in liver transplanted patients with multiple risk factors for AP, such as a history of repeated and complex abdominal surgery.

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Pancreatitis and pancreatic cancer in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists: an updated meta-analysis of randomized controlled trials

Cited by 9 publications

References 65 publications

The Use of Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus Does Not Increase the Risk of Pancreatic Cancer: A U.S.-Based Cohort Study

The Use of Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus Does Not Increase the Risk of Pancreatic Cancer: A U.S.-Based Cohort Study

Glucagon-like Peptide-1 Agonists

Case report: GLP1RA for the treatment of diabetes in liver transplanted people. Do they increase the risk of pancreatitis?

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