Swissmedic Vigilance News

However, in two other meta-analyses, again with
diabetic patients, cases of pancreatitis are described
as rare side effects of semaglutide. Only few studies
exist and, according to the authors, further assessment
supported by pharmacovigilance studies
is needed (18, 19).
While pancreatitis is not a known side effect of
SGLT-2 inhibitors, there have been several reported
cases associating their use with pancreatitis (20–23),
including one case with positive rechallenge and
dechallenge in a 51-year-old man with a history of
type 2 diabetes, dyslipidaemia and a cholecystectomy
(24). He was hospitalised for pancreatitis and,
following investigations, an alcoholic and biliary
origin, as well as hypercalcaemia and hypertriglyceridaemia,
were ruled out. Dapagliflozin had been
started five days before his admission, in addition to
his long-term treatment with insulin detemir, sitagliptin,
metformin and rosuvastatin. His symptoms
disappeared after the sitagliptin and dapagliflozin
were stopped. One year later, following an increase
in his HbA1c levels, it was decided to re-administer
the dapagliflozin. Subsequently, the patient developed
another episode of acute pancreatitis. His
symptoms resolved after the dapagliflozin was discontinued.
An analysis investigating the association
between SGLT-2 inhibitors and acute pancreatitis
utilised the postmarketing data collected between
2013 and 2021 in the American FAERS database
(FDA Adverse Event Reporting System) (25). In this
study, employing various statistical methods, the
authors concluded that the administration of SGLT-2
inhibitors may increase the risk of onset of acute
pancreatitis (with RORs of 5.37 for canagliflozin,
4.8 for dapagliflozin and 4.78 for empagliflozin).
In most cases, this side effect occurred within the first
six months after treatment initiation. When SGLT-2
inhibitors were combined with dipeptidyl peptidase-4
inhibitors (gliptins), GLP-1 analogues or angiotensin
converting enzyme inhibitors, the risk of
onset of acute pancreatitis was greater compared
to the administration of SGLT-2 inhibitors as monotherapy.
However, the data currently available do
not allow any definitive conclusion to be drawn
concerning the role of SGLT-2 inhibitors in the occurrence
of pancreatitis.
Conclusion
Although drug-induced pancreatitis accounts for a
small proportion of pancreatitis cases, it is important
to consider it in the differential diagnosis of
acute pancreatitis, so that the potentially responsible
drug(s) can be withdrawn. Nevertheless, establishing
a causality link is not always easy in view
of the presence of other, more prevalent causes,
particularly in patients with multiple comorbidities
and underlying risk factors. Moreover, in many cases
a conclusive association between a pancreatitis
and a particular drug cannot be determined due
to the absence of a rechallenge or an inconclusive
chronology. In such situation, the periodically updated
systems for classifying the association between
an adverse effect and treatment can greatly
assist clinicians, particularly for events that are as
rare as drug-induced pancreatitis.
References
(1) Nguyen-Tang T, Negrin DS, Vonlaufen A, Frossard J-L.
[Drug-induced pancreatitis]. Rev Med Suisse. 5 Sept
2007;3(123):1942, 1944–7.
(2) Chung EK, Lee JH, Jang DK, Lee SH, Lee JH, Park
B-J, et al. Causative Agents of Drug-Induced Pancreatitis:
A Nationwide Assessment. Pancreas.
2018;47(10):1328–36.
(3) Santhi Swaroop Vege, MD. Etiology of acute pancreatitis
[Internet]. Douglas G Adler, MD, FACG, AGAF,
FASGE; 2023 [cited 28 August 2023]. Availabe from:
https://www.uptodate.com/contents/etiology-of-acute-pancreatitis
(4) Wolfe D, Kanji S, Yazdi F, Barbeau P, Rice D, Beck A, et
al. Drug induced pancreatitis: A systematic review of
case reports to determine potential drug associations.
PLoS One. 2020;15(4):e0231883.
(5) Badalov N, Baradarian R, Iswara K, Li J, Steinberg W,
Tenner S. Drug-induced acute pancreatitis: an evidence-based
review. Clin Gastroenterol Hepatol. June
2007;5(6):648–61; quiz 644.
(6) Simons-Linares CR, Elkhouly MA, Salazar MJ. Drug-
Induced Acute Pancreatitis in Adults: An Update. Pancreas.
2019;48(10):1263–73.
Swissmedic Vigilance News | Edition 31 – November 2023
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