Liraglutide Overdose-Induced Acute Pancreatitis

AlSaadoun, Aljawhara R; AlSaadoun, Tariq R; Ghumlas, Abdullah K Al

doi:10.7759/cureus.21616

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…This is consistent with the increased risk of acute pancreatitis with DPP-4 inhibitors reported by Doni et al (Doni et al, 2022). It has previously been reported that GLP-1RA may cause acute pancreatitis (Smits and Van Raalte, 2021;AlSaadoun et al, 2022), but two recent network meta-analyses revealed that DPP-4 may increase the risk of acute pancreatitis, while GLP-1RA seems to have no effect (Kanie et al, 2021;Zhuo et al, 2021). However, there are no reports indicating whether the combination of GLP-1RA with SGLT-2i increases this risk.…”

Section: Discussionsupporting

confidence: 89%

Analysis of acute pancreatitis associated with SGLT-2 inhibitors and predictive factors of the death risk: Based on food and drug administration adverse event report system database

Zhang

Mao

et al. 2022

Front. Pharmacol.

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Background and objectives: The US FDA and Health Canada have successively published potential red flags for acute pancreatitis caused by sodium-dependent glucose transporter 2 inhibitors (SGLT-2i). However, existing studies have focused on case reports. We aimed to assess the possible association of SGLT-2i with acute pancreatitis by analyzing postmarketing adverse events reported in the FDA adverse event reporting system (FAERS), to explore risk factors for SGLT-2i-related acute pancreatitis death, and to build a nomogram.Methods and Results: We used a disproportionality analysis of suspected acute pancreatitis-related reports in the FAERS database of patients from the use of SGLT-2i from the first quarter of 2013 to the fourth quarter of 2021. Single-factor and multi-factor logistic regression analyses were performed using the relevant clinical information of patients, and risk factors were combined with the age of patients to construct a SGLT-2i risk prediction model for acute pancreatitis-related death. A total of 757 reports were retrieved. The largest number of acute pancreatitis-related cases were caused by canagliflozin (317 reports), which was also the strongest agent associated with acute pancreatitis, with the information component (IC 2.41, lower 95% one-sided confidence interval 2.16), the reporting odds ratio (ROR 5.37, 95% two-sided confidence interval 4.8–5.99), and the empirical Bayesian geometric mean (EBGM 5.32, lower 90% one-sided confidence interval 4.85). The median time to acute pancreatitis was 54 (interquartile range [IQR] 14–131) days, and approximately 83% of adverse events occurred within 6 months. Odds ratio(OR) adjusted by acute pancreatitis and the coadministration of SGLT-2i with dipeptidyl peptidase 4 inhibitor (DPP-4i), glucagon-like peptide 1 analog (GLP-1RA), and angiotensin converting enzyme inhibitor (ACEIs) was 1.39, 1.97, and 1.34, respectively, all of which were statistically significant. Logistic regression analysis showed that different SGLT-2i type and their combinations with statins were independent risk factors for acute pancreatitis mortality in the patients (p < 0.05). The mortality risk prediction model showed good discrimination and clinical applicability in both the training set (AUC 0.708) and the validation set (AUC 0.732).Conclusion: SGLT-2i may increase the risk of acute pancreatitis especially within the first 6 months of drug administration. Combination with DPP-4i, GLP-1RA or ACEIs significantly increases the risk of acute pancreatitis. In addition, different SGLT-2i type and their combination with statins are risk factors that can predict the risk of death following acute pancreatitis.

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Section: Discussionsupporting

confidence: 89%

Analysis of acute pancreatitis associated with SGLT-2 inhibitors and predictive factors of the death risk: Based on food and drug administration adverse event report system database

Zhang

Mao

et al. 2022

Front. Pharmacol.

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“…Liraglutide may also contribute to an increased risk of acute gallbladder or biliary disease. 168 , 169 …”

Section: Signaling Pathways Driving Nafl/nash Development and Related...mentioning

confidence: 99%

Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

Poulsen

et al. 2022

Sig Transduct Target Ther

131

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Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a focus on diabetes, hepatic lipid metabolism, inflammation, and fibrosis. Importantly, growing evidence elucidates that the disruption of the gut–liver axis and microbe-derived metabolites drive the pathogenesis of NAFL/NASH. Extracellular vesicles (EVs) act as a signaling mediator, resulting in lipid accumulation, macrophage and hepatic stellate cell activation, further promoting inflammation and liver fibrosis progression during the development of NAFL/NASH. Targeting gut microbiota or EVs may serve as new strategies for the treatment of NAFL/NASH. Finally, other mechanisms, such as cell therapy and genetic approaches, also have enormous therapeutic potential. Incorporating drugs with different mechanisms and personalized medicine may improve the efficacy to better benefit patients with NAFL/NASH.

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“…However, the use of LIRA faces challenges, especially with regard to adverse effects, such as nausea and diarrhea, in addition to causing liver and pancreatic problems [10][11][12]. There is also a need for administration by daily subcutaneous injection, which may impact treatment adherence [13].…”

Section: Introductionmentioning

confidence: 99%

Oral Delivery of Liraglutide-Loaded Zein/Eudragit-Chitosan Nanoparticles Provides Pharmacokinetic and Glycemic Outcomes Comparable to Its Subcutaneous Injection in Rats

Ziebarth,

da Silva,

Lorenzett

et al. 2024

Pharmaceutics

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Liraglutide (LIRA) is a glucagon-like peptide-1 (GLP-1) receptor agonist renowned for its efficacy in treating type 2 diabetes mellitus (T2DM) and is typically administered via subcutaneous injections. Oral delivery, although more desirable for being painless and potentially enhancing patient adherence, is challenged by the peptide’s low bioavailability and vulnerability to digestive enzymes. This study aimed to develop LIRA-containing zein-based nanoparticles stabilized with eudragit RS100 and chitosan for oral use (Z-ERS-CS/LIRA). These nanoparticles demonstrated a spherical shape, with a mean diameter of 238.6 nm, a polydispersity index of 0.099, a zeta potential of +40.9 mV, and an encapsulation efficiency of 41%. In vitro release studies indicated a prolonged release, with up to 61% of LIRA released over 24 h. Notably, the nanoparticles showed considerable resistance and stability in simulated gastric and intestinal fluids, suggesting protection from pH and enzymatic degradation. Pharmacokinetic analysis revealed that orally administered Z-ERS-CS/LIRA paralleled the pharmacokinetic profile seen with subcutaneously delivered LIRA. Furthermore, in vivo tests on a diabetic rat model showed that Z-ERS-CS/LIRA significantly controlled glucose levels, comparable to the results observed with free LIRA. The findings underscore Z-ERS-CS/LIRA nanoparticles as a promising approach for oral LIRA delivery in T2DM management.

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Liraglutide Overdose-Induced Acute Pancreatitis

Cited by 5 publications

References 18 publications

Analysis of acute pancreatitis associated with SGLT-2 inhibitors and predictive factors of the death risk: Based on food and drug administration adverse event report system database

Analysis of acute pancreatitis associated with SGLT-2 inhibitors and predictive factors of the death risk: Based on food and drug administration adverse event report system database

Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

Oral Delivery of Liraglutide-Loaded Zein/Eudragit-Chitosan Nanoparticles Provides Pharmacokinetic and Glycemic Outcomes Comparable to Its Subcutaneous Injection in Rats

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