Glucagon‐like peptide‐1 receptor agonists and risk of acute pancreatitis in patients with type 2 diabetes

Storgaard, Heidi; Cold, Frederik; Gluud, Lise Lotte; Vilsbøll, Tina; Knop, Filip K.

doi:10.1111/dom.12885

Cited by 104 publications

(69 citation statements)

References 16 publications

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“…A study found a more than 10-fold increase in reported pancreatitis and 2.9-fold increase in reported pancreatic cancer in patients treated with exenatide compared to other therapies using the FDA Adverse Event Reporting System (FAERS) database. 255 A retrospective cohort study involving almost one million patients initiating antidiabetic medications also showed no increased risk of pancreatic cancer with GLP-1R agonists use. 253 To address this concern, both the FDA and EMA reviewed the preclinical and clinical studies regarding the risk of pancreatitis and pancreatic cancer and concluded that the data were inconsistent with a causal association between GLP-1R agonists and pancreatic adverse events.…”

Section: Safety Issues and Tolerabilitymentioning

confidence: 99%

Incretins in obesity and diabetes

Chia

Egan

2019

Annals of the New York Academy of Sciences

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Incretins are hormones secreted from enteroendocrine cells after nutrient intake that stimulate insulin secretion from β cells in a glucose‐dependent manner. Glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are the only two known incretins. Dysregulation of incretin secretion and actions are noted in diseases such as obesity and diabetes. In this review, we first summarize our traditional understanding of the physiology of GIP and GLP‐1, and our current knowledge of the relationships between GIP and GLP‐1 and obesity and diabetes. Next, we present the results from major randomized controlled trials on the use of GLP‐1 receptor agonists for managing type 2 diabetes, and emerging data on treating obesity and prediabetes. We conclude with a glimpse of the future with possible complex interactions between nutrients, gut microbiota, the endocannabinoid system, and enteroendocrine cells.

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Section: Safety Issues and Tolerabilitymentioning

confidence: 99%

Incretins in obesity and diabetes

Chia

Egan

2019

Annals of the New York Academy of Sciences

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“…These adverse reactions tend to improve after a few weeks, and some of the short‐acting forms of GLP1 receptor agonist can be commenced at a low dose and uptitrated over several weeks to minimise their occurrence. There have also been concerns regarding an increased risk of acute pancreatitis in post‐marketing studies, although a more recent meta‐analysis of randomised controlled trials did not find any association between GLP1 receptor agonist use and acute pancreatitis . The risk of pancreatitis is probably overstated at present, but the medication should be ceased permanently if pancreatitis develops, and GLP1 receptor agonists should be avoided in patients with a prior history of pancreatitis.…”

Section: Glucagon‐like Peptide 1 Receptor Agonistsmentioning

confidence: 99%

Advances in type 2 diabetes therapy: a focus on cardiovascular and renal outcomes

Libianto

Davis

Ekinci

2020

Medical Journal of Australia

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Summary Treatment options for type 2 diabetes have expanded. While metformin remains the first line treatment in most cases, choices for second line treatment now extend beyond sulfonylureas and include the sodium–glucose cotransporter 2 (SGLT2) inhibitors, glucagon‐like peptide 1 (GLP1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors. SGLT2 inhibitors are recommended for people with atherosclerotic cardiovascular disease, heart failure or kidney disease. Diabetic ketoacidosis is an uncommon but important side effect; its occurrence can be minimised with appropriate patient education and management, especially during perioperative periods and times of illness. GLP1 receptor agonists are recommended for people with atherosclerotic cardiovascular disease. Gastrointestinal side effects are common but are less prominent with the longer acting agents and can be minimised with slow titration of the shorter acting agents. DPP4 inhibitors are generally well tolerated, but alogliptin and saxagliptin should be used with caution in people with risk factors for heart failure. To optimise the management of type 2 diabetes, clinicians need to be aware of the pharmacological characteristics of each class of blood glucose‐lowering medications and of the effect on cardiovascular health and renal function, balanced by potential adverse effects. Medications that have cardiovascular or renal benefits should be prescribed for patients with these comorbidities, and this is reflected in recent international guidelines.

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“…A sub‐group analysis including only trials with adjudication of AP had similar results (M‐H OR, 0.87 [95% CI, −0.53‐1.44]). Another meta‐analysis of three RCTs of GLP‐1 therapies looking at AP as a predefined and independently adjudicated adverse event also found no elevated risk in T2D patients (Peto OR, 0.745 [95% CI, 0.47‐1.17]) . This result is in contrast to that of two similar meta‐analyses of DPP‐4 i RCT that found significant increases in AP risk in the treatment group vs controls.…”

Section: Discussionmentioning

confidence: 84%

Liraglutide use and evaluation of pancreatic outcomes in a US commercially insured population

Funch

Mortimer

Ziyadeh

et al. 2019

Diabetes Obesity Metabolism

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Aims Both acute pancreatitis (AP) and pancreatic cancer (PC) have been areas of focus for studies of incretin drugs. This 5‐year prospective cohort study aimed to quantify possible associations between liraglutide and risk of AP and PC as compared to other antidiabetic drugs (ADs). Materials and methods Patients initiating liraglutide or other ADs who were enrolled in a US health plan (2010‐2014) were included. Comparisons of AP and PC incidence rates were made between matched cohorts of liraglutide initiators and initiators of other ADs. Adjudicated AP cases and algorithm‐based PC cases were identified. Propensity score‐matched intention‐to‐treat (ITT) and time‐on‐drug (TOD) analyses were completed using Poisson regression. A latency analysis was performed for PC. Results Median follow‐up was 405 days for AP cohorts (9995 liraglutide, 1:1 matched to all comparators) and 503 days for PC cohorts (35 163 liraglutide, 1:1 matched to all comparators). In the primary AP analysis, “current” use of liraglutide was not significantly associated with elevated risk across comparators (all comparators relative risk [RR] = 1.2; 95% confidence interval [CI], 0.6‐2.3). ITT results were similar where, in the primary analysis, no RRs were significantly associated with PC (all comparators RR = 0.7; 95% CI, 0.3‐1.4); latency and TOD analyses did not alter findings. There was no evidence of a dose‐response effect. Conclusions Liraglutide was not associated with an increased risk of AP or PC, although risk estimates were more variable for AP, and numbers of cases for both outcomes were limited because of the rarity of outcomes.

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Glucagon‐like peptide‐1 receptor agonists and risk of acute pancreatitis in patients with type 2 diabetes

Cited by 104 publications

References 16 publications

Incretins in obesity and diabetes

Incretins in obesity and diabetes

Advances in type 2 diabetes therapy: a focus on cardiovascular and renal outcomes

Liraglutide use and evaluation of pancreatic outcomes in a US commercially insured population

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