Incretin-based therapies and acute pancreatitis risk: a systematic review and meta-analysis of observational studies

Giorda, Carlo; Sacerdote, Carlotta; Nada, Elisa; Marafetti, Lisa; Baldi, Ileana; Gnavi, Roberto

doi:10.1007/s12020-014-0386-8

Cited by 59 publications

(51 citation statements)

References 36 publications

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“…In contrast to the above results, several recent studies and meta-analyses failed to show increased risk of pancreatitis with the use of GLP-1 receptor agonists [72][73][74][75][76][77][78][79][80][81][82]. A meta-analysis of 55 randomized controlled trials (n = 33,350) showed no increased risk of pancreatitis with GLP-1 agonists compared with controls (OR: 1.05, 95% CI: 0.37-2.94) [83].…”

Section: Pancreasmentioning

confidence: 78%

Adverse Effects of GLP-1 Receptor Agonists

2014

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■ AbstractGlucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related parameters in patients with type 2 diabetes (T2D). However, the use of this relatively new class of drugs may be associated with certain adverse effects. Concerns have been expressed regarding the effects of these drugs on pancreatic and thyroid tissue, since animal studies and analyses of drug databases indicate an association of GLP-1 receptor agonists with pancreatitis, pancreatic cancer, and thyroid cancer. However, several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects. One benefit of GLP-1 receptor agonists is that they do not cause hypoglycemia when combined with metformin or thiazolidinediones, but the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes. On the other hand, several case reports have linked the use of these drugs, mainly exenatide, with the occurrence of acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea. The most common symptoms associated with the use of GLP-1 receptor agonists are gastrointestinal symptoms, mainly nausea. Other common adverse effects include injection site reactions, headache, and nasopharyngitis, but these effects do not usually result in discontinuation of the drug. Current evidence shows that GLP-1 receptor agonists have no negative effects on the cardiovascular risk of patients with T2D. Thus, GLP-1 receptor agonists appear to have a favorable safety profile, but ongoing trials will further assess their cardiovascular effects. The aim of this review is to analyze critically the available data regarding adverse events of GLP-1 receptor agonists in different anatomic systems published in Pubmed and Scopus. Whenever possible, certain differences between GLP-1 receptor agonists are described. The review also provides the reader with structured data that compare the rates of the most common adverse effects for each of the various GLP-1 receptor agonists.

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Section: Pancreasmentioning

confidence: 78%

Adverse Effects of GLP-1 Receptor Agonists

2014

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“…The study reported by Giorda et al in this issue of Endocrine helps us to be more reassured about the safety of incretinbased therapies in the management of T2DM [11]. However, we should also keep in mind that our experience of slightly more than a decade is still insufficient to judge the long-term safety of this class of medications that may have effects in many body tissues.…”

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confidence: 97%

“…A systematic review and meta-analysis addressing this issue published early this year concluded that evidence for increased incidence of pancreatitis in T2DM patients taking incretin mimetics is inadequate, and that incretinbased therapies do not increase pancreatitis risk [10]. The studies analysed in this paper provided robust data from a total patient population of 33,350 cases treated for a median duration of 26 weeks that helped clearing the uncertainty to some extent.Giorda et al in this issue of Endocrine provide further evidence using a different search strategy on the lack of definite association between incretin-based therapies and pancreatitis risk through another systematic review and meta-analysis [11]. They analysed 136 abstracts from PubMed electronic database of which 15 full-text articles were reviewed in detail.…”

mentioning

confidence: 99%

“…Giorda et al in this issue of Endocrine provide further evidence using a different search strategy on the lack of definite association between incretin-based therapies and pancreatitis risk through another systematic review and meta-analysis [11]. They analysed 136 abstracts from PubMed electronic database of which 15 full-text articles were reviewed in detail.…”

mentioning

confidence: 99%

“…These studies [10,11] shall clearly weaken the impact of propaganda about the very high risk of pancreatitis of more than ten-fold from incretin mimetic drugs projected through adverse event reporting systems [12]. Alerts from the FDA and European agencies about high risk of pancreatitis followed by widespread media coverage on the matter created a big pandemonium globally among the public on the safety of these medications.…”

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confidence: 99%

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Incretin-based therapies and pancreatitis risk: myth or reality

Pappachan

2014

Endocrine

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Incretins are gastrointestinal hormones secreted in response to food intake that modify biological mechanisms of glucose homeostasis in the body. Approximately 70 % of insulin secretion by pancreatic b-cells is under the control of two incretin molecules, namely glucose-dependent intestinal polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) [1]. Endogenous GLP-1 is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4) to an inactive molecule that terminates its incretin effect. Research on the pharmacological manipulation of GLP-1 and DPP-4 molecules resulted in the development of multiple drugs in recent years, which are very useful for the treatment of type 2 diabetes mellitus (T2DM). These drugs, the GLP-1 analogues and DPP-4 inhibitors, form the incretin-based therapies in the management of T2DM, collectively termed as incretin mimetics or incretin analogues. With a modest effect on haemoglobin A1c, favourable effects on body weight and relatively low risk of hypoglycaemia [2], these drugs gained much popularity in the past few years. Incretin-based therapies are recommended by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) as second-line agents for the management of T2DM [2,3].The meal-related insulin release from pancreas results from the binding of GLP-1 to b-cell GLP-1 receptors (GLP-1R). Because of the very short biological half-life, endogenously produced GLP-1 does not possess sustained effects on the pancreas. However, incretin mimetic drugs result in continued stimulation of GLP-1R with a potential for pleotropic effects on the pancreatic tissues [4].Experimental data from animal models showed conflicting results with some studies showing evidence of pancreatic damage from incretin mimetics [5,6], whereas the others demonstrating protective effects [7,8]. Concerns were raised about the risk for pancreatic damage from incretinbased therapies based on multiple case reports and recent data from the United States Food and Drug Administration (FDA) adverse events reporting system. These prompted the FDA and other international agencies to caution the global medical fraternity about the potential harm related to the use of this new class of medications which were deemed to be promising in the management of T2DM, especially in obese individuals.The warnings from different global agencies evoked a hot international debate on the safety of incretin-based therapies in 2013 [4,9]. Several reports from the FDA and other international agencies also added chaos to the discussion although none has resolved the uncertainty completely. A systematic review and meta-analysis addressing this issue published early this year concluded that evidence for increased incidence of pancreatitis in T2DM patients taking incretin mimetics is inadequate, and that incretinbased therapies do not increase pancreatitis risk [10]. The studies analysed in this paper provided robust data from a total patient population of 33,350 cases treated for a median duration of 26 wee...

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Diabetes Mellitus Related to Diseases of the Exocrine Pancreas (Pancreatogenic Diabetes)

Bradley

Hart

2021

Clinical Pancreatology for Practising Gastroenterologists and Surgeons

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Incretin-based therapies and acute pancreatitis risk: a systematic review and meta-analysis of observational studies

Cited by 59 publications

References 36 publications

Adverse Effects of GLP-1 Receptor Agonists

Adverse Effects of GLP-1 Receptor Agonists

Incretin-based therapies and pancreatitis risk: myth or reality

Diabetes Mellitus Related to Diseases of the Exocrine Pancreas (Pancreatogenic Diabetes)

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