Incretin therapies and risk of hospital admission for acute pancreatitis in an unselected population of European patients with type 2 diabetes: a case-control study

Giorda, Carlo; Picariello, Roberta; Nada, Elisa; Tartaglino, Barbara; Marafetti, Lisa; Costa, Giuseppe; Gnavi, Roberto

doi:10.1016/s2213-8587(13)70147-5

Cited by 37 publications

(37 citation statements)

References 17 publications

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“…That study was restricted to individuals younger than 65 years of age (~60% of our study population was in this age group), who had no data on liraglutide use but only sitagliptin and exenatide use (which were used by 65% of incretin users in our data set), and included no confounder data on other pancreatitis-related drugs. In another recent, population-based case-control analysis in Piedmont, Italy, Giorda et al (25) found that current use of incretins versus other antihyperglycemic drugs was not associated with acute pancreatitis (adjusted OR 0.98 [95% CI 0.69-1.38]), which is consistent with our result. Compared with Singh et al (24), Giorda et al (25) examined all types of incretins, and used population-based data on unselected patients of all ages, similar to our study.…”

Section: Discussionsupporting

confidence: 92%

“…These studies include several cohort analyses from the U.S. (20)(21)(22) and U.K. (23). In contrast, a casecontrol study in the U.S. reported an adjusted OR of 2.24 (95% CI 1.36-3.68) for acute pancreatitis (24) associated with the use of exenatide or sitagliptin, while another Italian case-control study (25) reported an adjusted OR of 0.98 (95% CI 0.69-1.38). Thus, the issue of the relationship of incretins and acute pancreatitis remains under debate.…”

mentioning

confidence: 99%

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Incretin-Based Therapy and Risk of Acute Pancreatitis: A Nationwide Population-Based Case-Control Study

et al. 2015

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OBJECTIVETo investigate whether the use of incretin-based drugs (GLP-1 receptor agonists and dipeptidyl peptidase 4 [DPP4] inhibitors) is associated with acute pancreatitis. RESEARCH DESIGN AND METHODSThe study was a nationwide population-based case-control study using medical databases in Denmark. Participants were 12,868 patients with a first-time hospitalization for acute pancreatitis between 2005 and 2012 and a population of 128,680 matched control subjects. The main outcome measure was the odds ratio (OR) for acute pancreatitis associated with different antihyperglycemic drugs. We adjusted for history of gallstones, alcoholism, obesity, and other pancreatitisassociated comorbidities and medications. RESULTSA total of 89 pancreatitis patients (0.69%) and 684 control subjects (0.53%) were ever users of incretins. The crude OR for acute pancreatitis among incretin users was 1.36 (95% CI 1.08-1.69), while it was 1.44 (95% CI 1.34-1.54) among users of other antihyperglycemic drugs. After confounder adjustment, the risk of acute pancreatitis was not increased among incretin users (OR 0.95 , compared with nonusers of any antihyperglycemic drugs. Findings were similar in current versus ever drug users and in patients with pancreatitis risk factors. The adjusted OR comparing incretinbased therapy with other antihyperglycemic therapy internally while also adjusting for diabetes duration and complications was 0.97 (95% CI 0.76-1.23). CONCLUSIONSOur findings suggest that the use of incretin-based drugs appears not to be associated with an increased risk of acute pancreatitis.Incretin-based therapies represent a new and widely used class of oral antihyperglycemic drugs for the treatment of type 2 diabetes (1). These agents currently include three injectable incretin mimetic agents (GLP-1 receptor agonists: exenatide, liraglutide, and lixisenatide), five incretin enhancers (dipeptidyl peptidase 4 [DPP4] inhibitors: sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin [not currently licensed in Denmark]), and combinations of these DPP4 inhibitors with metformin or

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Section: Discussionsupporting

confidence: 92%

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confidence: 99%

Incretin-Based Therapy and Risk of Acute Pancreatitis: A Nationwide Population-Based Case-Control Study

et al. 2015

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“…These concerns have been corroborated by reports from adverse event databases (4,5), although such analyses have well-known limitations. In contrast, the observational studies conducted to date have been conflicting and inconclusive (6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

Section: Dwilliam T Cefalu Editor In Chief Diabetes Carementioning

confidence: 99%

Incretin-Based Drugs and Adverse Pancreatic Events: Almost a Decade Later and Uncertainty Remains

Azoulay

2015

Diabetes Care

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Over the past few years, substantial clinical data have been presented showing that incretin-based therapies are effective glucose-lowering agents. Specifically, glucagon-like peptide 1 receptor agonists demonstrate an efficacy comparable to insulin treatment with minimal hypoglycemia and have favorable effects on body weight. Thus, many of the unmet clinical needs noted from prior therapies are addressed by these agents. However, even after many years of use, many continue to raise concerns about the long-term safety of these agents and, in particular, the concern with pancreatitis. This clearly remains a complicated topic. Thus, in this issue of Diabetes Care, we continue to update our readers on this very important issue by presenting two studies evaluating incretin-based medications and risk of pancreatitis. Both have undergone significant revisions based on peer review that provided significant clarification of the data. We applaud both author groups for being extremely responsive in providing the additional data and revisions requested by the editorial team. As such, because of the critical peer review, we feel both articles achieve the high level we require for Diabetes Care and are pleased to now present them to our readers. In keeping with our aim to comprehensively evaluate this topic, we asked for additional commentaries to be prepared. In the narrative outlined below, Dr. Laurent Azoulay provides a commentary about the remaining uncertainty in this area and also discusses the results from a nationwide population-based case-control study. In the narrative preceding Dr. Azoulay’s contribution, Prof. Edwin A.M. Gale provides a commentary on the report that focuses on clinical trials of liraglutide in the treatment of diabetes. From the journal’s perspective, both of the articles on pancreatitis and incretin-based therapies reported in this issue have been well vetted, and we feel both of the commentaries are insightful. —William T. Cefalu Editor in Chief, Diabetes Care

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“…A recent study also suggested that pancreatic findings attributed to incretin-based therapies in rodents are commonly observed background findings, without any drug treatment and independent of diet or glycemic status [110] . Moreover large retrospective population studies and recent metaanalysis suggested a negative association of incretinbased therapies with either pancreatitis or pancreatic cancer [111][112][113][114][115][116][117][118][119][120] . Recently the FDA reevaluated more than 250 toxicology studies, organized in nearly 18000 healthy animals, and found no association with pancreatitis or any pancreatic toxicity.…”

Section: Safety Of Incretin-based Therapiesmentioning

confidence: 99%

Incretin-based therapies in prediabetes: Current evidence and future perspectives

Papaetis¹

2014

WJD

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The prevalence of type 2 diabetes (T2D) is evolving globally at an alarming rate. Prediabetes is an intermediate state of glucose metabolism that exists between normal glucose tolerance (NGT) and the clinical entity of T2D. Relentless β-cell decline and failure is responsible for the progression from NGT to prediabetes and eventually T2D. The huge burden resulting from the complications of T2D created the need of therapeutic strategies in an effort to prevent or delay its development. The beneficial effects of incretin-based therapies, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, on β-cell function in patients with T2D, together with their strictly glucose-depended mechanism of action, suggested their possible use in individuals with prediabetes when greater β-cell mass and function are preserved and the possibility of β-cell salvage is higher. The present paper summarizes the main molecular intracellular mechanisms through which GLP-1 exerts its activity on β-cells. It also explores the current evidence of incretin based therapies when administered in a prediabetic state, both in animal models and in humans. Finally it discusses the safety of incretin-based therapies as well as their possible role in order to delay or prevent T2D.© 2014 Baishideng Publishing Group Inc. All rights reserved. Key words:Type 2 diabetes; Prediabetes; Impaired fasting glucose; Impaired glucose tolerance; Glucagonlike peptide-1; Dipeptidyl peptidase-4 inhibitors; Glucagon-like peptide-1 receptor agonists Core tip: The beneficial effects of incretin-based therapies on β-cell function in patients with type 2 diabetes (T2D) suggested their possible use in individuals with prediabetes, when greater β-cell mass and function are preserved. Both dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have demonstrated improvements on β-cell function both in preclinical studies and short-term clinical studies. Until future date for their safety are available, large, long term, prevention trials will be required in order to determine whether they can stabilize or reverse β-cell loss and promote a sustained reduction in the development of T2D in this population.Papaetis GS. Incretin-based therapies in prediabetes: Current evidence and future perspectives. World J Diabetes 2014; 5(6): 817-834 Available from:

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Incretin therapies and risk of hospital admission for acute pancreatitis in an unselected population of European patients with type 2 diabetes: a case-control study

Cited by 37 publications

References 17 publications

Incretin-Based Therapy and Risk of Acute Pancreatitis: A Nationwide Population-Based Case-Control Study

Incretin-Based Therapy and Risk of Acute Pancreatitis: A Nationwide Population-Based Case-Control Study

Incretin-Based Drugs and Adverse Pancreatic Events: Almost a Decade Later and Uncertainty Remains

Incretin-based therapies in prediabetes: Current evidence and future perspectives

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