A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position

Giorda, Carlo; Nada, Elisa; Tartaglino, Barbara; Marafetti, Lisa; Gnavi, Roberto

doi:10.1111/dom.12297

Cited by 21 publications

(19 citation statements)

References 58 publications

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“…Generally, no direct cause and effect relationship has been shown between GLP-1 receptor agonists and pancreatitis [86]. Moreover, T2D and hypertriglyceridemia are both independent risk factors for pancreatitis [87,88].…”

Section: Pancreasmentioning

confidence: 99%

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: 99%

Adverse Effects of GLP-1 Receptor Agonists

2014

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“…Many of the drugs prescribed in pharmacies routinely are suspected of causing AP. In addition, they pose a high risk with cumulative doses (Giorda et al 2014;Oliveira et al 2014).…”

Section: Introductionmentioning

confidence: 99%

The carvacrol ameliorates acute pancreatitis-induced liver injury via antioxidant response

et al. 2015

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Acute pancreatitis (AP) may cause significant persistent multi-organ dysfunction. Carvacrol (CAR) possesses a variety of biological and pharmacological properties. The aim of the present study was to analyze the hepatic protection of CAR on AP induced by cerulein and to explore the underlying mechanism using in vivo studies. The rats were randomized into groups to receive (1) no therapy; (2) 50 lg/kg cerulein at 1-h intervals by four intraperitoneal injection (i.p.); (3) 50, 100 and 200 mg/kg CAR by one i.p.; and (4) cerulein ? CAR after 2 h of cerulein injection. 12 h later, serum was provided to assess the blood AST, ALT and LDH values. Also, liver tissues were obtained for histological and biochemical measurements. Liver oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as MDA and changes in tissue antioxidant enzyme levels, SOD, CAT and GSHPx. Histopathological examination was performed using scoring systems. Oxidative damage to DNA was quantitated in studied tissues of experimental animals by measuring the increase in 8-hydroxydeoxyguanosine (8-OHdG) formations. We found that the increasing doses of CAR decreased pancreatitisinduced MDA and 8-OH-dG levels. Moreover, the liver SOD, CAT and GSH-Px activities in the AP ? CAR group were higher than that of the rats in the AP group. In the treatment groups, AST, ALT and LDH were reduced. Besides, necrosis, coagulation and inflammation in the liver were alleviated (p \ 0.05). We suggest that CAR could be a safe and potent new drug candidate for treating AP through its antioxidative mechanism of action for the treatment of a wide range of disorders related to hepatic dysfunction.

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“…Recent research efforts demonstrate a major role of oxidative stress risk in the development, and progression of most pancreatic diseases, including recurrent acute and chronic pancreatitis (Robles et al 2013). Drugs have been shown to increase the risk of developing AP (Stobaugh and Deepak 2014;Giorda et al 2014;Oliveira et al 2014). And the supplementation of certain medicinal herbal extracts with drug may reduce the stress caused by drugs (Lata et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Carvacrol modulates oxidative stress and decreases cell injury in pancreas of rats with acute pancreatitis

et al. 2015

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Acute pancreatitis (AP) is considered as major problem around the world and the incidence of AP is increasing. Carvacrol (CAR), a monoterpenic phenol, has good antioxidant activity. This in vivo study was designed to evaluate whether CAR provide protection against AP that developed by pancreas injury. The rats were randomised into groups to receive (I) no therapy; (II) 50 lg/kg cerulein at 1 h intervals by four intraperitonally (i.p.) injections; (III) 50, 100 and 200 mg/kg CAR by one i.p. injection; and (IV) cerulein plus CAR after 2 h of cerulein administration. 12 h later, serum samples were obtained to assess pancreatic function, the lipase and amylase values. The oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde (MDA) and changes in main tissue antioxidant enzyme levels including SOD, CAT and GSH-PX. Histopathological examination was performed using scoring systems. Additionally, oxidative DNA damage was determined by measuring the increases of 8-hydroxy-deoxyguanosine (8-OH-dG) formations. We found that the increasing doses of CAR decreased AP-induced MDA and 8-OH-dG levels. Moreover, the pancreas antioxidant enzyme activities were higher than that of the rats in the AP group when compared to the AP plus CAR group. In the treatment groups, the lipase and amylase were reduced. Besides, histopathological findings in the pancreatic tissue were alleviated (p \ 0.05). We suggest that CAR could be a safe and potent new drug candidate for treating AP through its antioxidative mechanism of action for the treatment of a wide range of disorders related to pancreas.

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A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position

Cited by 21 publications

References 58 publications

Adverse Effects of GLP-1 Receptor Agonists

Adverse Effects of GLP-1 Receptor Agonists

The carvacrol ameliorates acute pancreatitis-induced liver injury via antioxidant response

Carvacrol modulates oxidative stress and decreases cell injury in pancreas of rats with acute pancreatitis

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