the incidence of acute pancreatitis is increasing around the world , where it is associated with morbidity and even the risk of mortality .
it may presents with various skin manifestations as rash and rarely , with erythematous tender subcutaneous nodules , known as pancreatic panniculitis .
alcohol and gallstones are the most important causes , while routinely prescribed drugs have been linked to the causation of acute pancreatitis .
metformin , one of the most widely prescribed oral hypoglycemic agents , was linked to pancreatitis , secondary to overdose or in case of impaired renal function . here
, we report a case of metformin induce acute pancreatitis in young healthy man with normal renal function .
nineteen year - old - man , known case of type 2 diabetes mellitus for 4 y on 1 g metformin twice daily since diagnosis of his diabetes .
he was in his usual state of health till he presented to the emergency department reporting nausea , vomiting and epigastric pain for 3 d. on physical examination , his height was 170 cm and body weight 99 kg ; body mass index ( bmi ) 34.3 kg / m2 , looked mildly dehydrated .
laboratory investigations showed hba1c 7.7% , creatinine 58 mol / l , amylase 462 units / l ( normal range < 100 ) , lipase 1378 units / l ( 060 ) , white blood cells 16.8/mm3 ( 411 ) 80% of which was neutrophils , crp 258 mg /
l ( 05 ) , mg 0.76 mmol / l ( 0.71.05 ) , ca 2.17 mmol / l ( 2.22.6 ) , ast 18 units / l ( < 39 ) , alt 34 units / l ( < 41 ) , tg 0.95 mmol / l ( < 2.3 ) , lactate 1.4 mmol / l ( 0.51.6 ) .
abdominal ultrasound and ercp were done for the patient , results showed no gallstones and clear biliary tract , respectively .
normalization of amylase and lipase was reached after metformin cessation , and supportive treatment in the form of iv insulin and iv fluids .
few days later , after re - exposure to metformin , he presented with recurrence of his previous symptoms , and elevation of amylase and lipase was documented . as a result , metformin was suspended with improvement of his symptoms and biochemical profile .
metformin is one of the most effective and valuable oral hypoglycemic agents in the biguanide class .
it has been selected as the drug of choice in management of majority of patients with type 2 diabetes mellitus , as it works by several mechanisms ; decreasing hepatic gluconeogenesis , increasing glucose transport into glucose utilizing cells , decreasing appetite and caloric intake and reducing intestinal glucose absorption . as any other medication , metformin
is associated with undesirable side effects and it has been reported in few cases to cause lactic acidosis and pancreatitis .
acute pancreatitis is attributed to many etiological factors ; one of them is medication , where a large number of single case reports on drug - induced pancreatitis were published .
diuretics , antimicrobial agents , hiv therapy and neuropsychiatric agents as well as metformin are known medication to induce pancreatitis .
the underlying pathogenesis in drug induced pancreatitis in some medications as codeine was due to spasm of sphincter of oddi , in others as azathioprine , immune- mediated mechanism or a hypersensitivity to the drug is the postulated pathogenesis . in metformin
, the exact mechanism is not known , but toxicity is probably secondary to acinar cell injury leading to intercellular leakage of digestive enzymes from ductules .
fortunately , drug - induced pancreatitis is an acute edematous pancreatitis of a benign course and good prognosis , but fatal outcome may ensue if proper management is not initiated . among the published case reports of
metformin induced pancreatitis , one was attributed to metformin overdose , other was caused by metformin accumulation , resulting from combination of drug overdose and acute renal failure triggered by vomiting in patient with concealed renal insufficiency .
additionally , two case reports were found to be associated with drug induced ( angiotensin converting enzyme inhibitor , angiotensin receptor blocker , non - steroidal anti - inflammatory drug as ibuprofen and celecoxib and diuretics ) renal failure , which reduced excretion of therapeutic dose of metformin causing toxicity , leading to sever lactic acidosis and pancreatitis .
lastly , in a case report of patient presented with hyperglycemia after an ingested dose between 64- 85 g of metformin in a suicide attempt , the potential mechanism of hyperglycemia is not clear and nothing among metformin s known mechanisms would logically explain the progressive and severe hyperglycemia , pancreatitis remains a potential mechanism , as the patient s clinical presentation with reportts vomiting and abdominal pain is consistent with pancreatitis . in our case , several signs can guide to and support the diagnosis of metformin induced pancreatitis ; first is the clinical presentation of abdominal pain , nausea , vomiting and dehydration .
second , high levels of lipase and amylase , which correlate positively with ct findings .
the lack of other known causes of acute pancreatitis such as gall stones , alcohol abuse , hypercalcaemia , hypertriglyceridaemia , and trauma , added more evidence to the diagnosis .
apart from the therapeutic dose of metformin ( 2 g daily ) , our patient has never consumed any other medications known to cause pancreatitis .
finally , resolution of his symptoms upon metformin cessation and relapse upon re - exposure would strongly suggest that metformin is deemed responsible of our patient s clinical presentation .
available evidence suggests that acute pancreatitis in our patient was probably precipitated by therapeutic dose of metformin with normal renal function , with unknown exact mechanism .
in summary , our case demonstrates the possibility of metformin to induce pancreatitis in a healthy patient without preexisting renal disease .
accordingly , every diabetic patient on metformin should be counseled about symptoms of acute pancreatitis and the urgency to discontinue metformin and visit the emergency department to receive the appropriate treatment . and
for us as physicians , metformin should be kept in back of our minds as a cause that would contribute to acute pancreatitis even in a healthy patient .
 acute pancreatitis frequently presents with abdomen pain but may presents with various skin manifestations as rash and rarely , pancreatic panniculitis . 
 metformin , one of the most effective and valuable oral hypoglycemic agents in the biguanide class was linked to acute pancreatitis in few cases . here 
 , we report a case of metformin induce acute pancreatitis in young healthy man with normal renal function . 