with the incidence of obesity on the rise , an increasing number of patients are being frequently diagnosed with complications secondary to their high body mass index . diabetes mellitus ( dm ) , hyperlipidemia , and coronary artery disease are a few of the more common diseases that seem to affect such individuals . although several studies have been conducted to evaluate the safety profiles and interactions among the drug groups used to treat and manage these illnesses , unusual side effects may still arise in some patients.15 we aim to create awareness regarding one of the frequently used combinations of drugs , namely , sitagliptin and atorvastatin , the use of which resulted in rhabdomyolysis of the skeletal muscle in a patient . although an isolated case , we propose and encourage further clinical trials in this area . a 60-year - old female with past medical history significant for hypertension , dm , coronary artery disease , and hyperlipidemia presented to the emergency room with the chief complaint of chest pain . she also reported generalized weakness , myalgias , subjective fever , and chills progressively worsening over the past 7 days . her physical examination showed stable vital signs and was otherwise unremarkable except for trace peripheral edema . the university of florida does not require irb approval or written informed consent for any case report with 3 or fewer patients as it is not a clinical study . fearing a coronary event , she was given a dose of sublingual nitroglycerine and aspirin . laboratory workup was significant for elevated creatinine phosphokinase ( cpk ) of 13,456 u / l ( reference range : 30170 u / l ) , normal troponin - t , normal complete blood count , and basic metabolic panel except elevated creatinine of 1.20 mg / dl ( reference range : 0.400.90 mg / dl ) . cpk levels evaluated in 2012 on this patient while on statins were unremarkable ( 191 u / l , 165 u / l , and 197 u / l , with reference range of 30170 she was admitted to the hospital due to concern for acute coronary event , rhabdomyolysis , acute renal insufficiency , and possible acute viral infection causing her symptoms . her workup during hospital stay showed three normal serial troponin - t tests , and myocardial perfusion test revealed no abnormality . there was no history of recent trauma , crush injury , prolonged immobilization , recent surgery , seizures , drug abuse , or alcoholism . her family history was negative for any kind of myopathy or other hereditary or genetic causes that could explain the elevated cpk value . her laboratory workup , including thyroid function tests , was unremarkable and failed to explain this episode of rhabdomyolysis . she had been on a stable dose of atorvastatin ( 40 mg ) for several years for hyperlipidemia and reported no myalgias , arthralgias , or abnormal cpk levels . review of her medication list further revealed that she was started on sitagliptin ( januvia 100 mg ) almost a week before this presentation . sitagliptin and atorvastatin were stopped ; her subsequent cpk value showed a decreasing trend and was recorded at 1,220 u / l on the day of discharge . the patient s muscle aches and chest pain had reduced considerably following the discontinuation of these medications rhabdomyolysis is potentially a serious clinical condition that involves breakdown of muscle tissue , releasing myoglobin into the blood . it can be caused by injuries to the skeletal muscles , which include trauma or crush injuries , severe exertion , dehydration , genetic muscle diseases , elevated body temperature , muscle tissue ischemia , electrolyte imbalance , and seizures , and can sometimes result from drug interactions . a few signs and symptoms of rhabdomyolysis include body aches , generalized weakness , myalgia , fever , and sometimes hematuria . atorvastatin belongs to the family of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme a ( hmg - coa ) reductase , frequently known as statins , responsible for the conversion of hmg - coa to mevalonate , preventing the cholesterol synthesis pathway . it is metabolized to its active metabolites , ortho- and para - hydroxylated forms , which are responsible for a majority of reactions . atorvastatin is a substrate for hepatic cytochrome p450 ( cyp ) 3a4 , as well as p - glycoprotein and the transporter organic anion - transporting polypeptide 1b1 ( oatp1b1).68 this in turn tends to cause significant drug interactions with other cyp3a4 inhibitors , which may result in potential complications such as myopathies . sitagliptin belongs to a newer class of agents known as dipeptidyl peptidase 4 ( dpp - iv ) inhibitors approved in 2006 by the us food and drug administration ( fda ) for the treatment of type 2 dm . dpp - iv inhibitors slow down the inactivation of incretin hormones ( glucagon - like peptide-1 [ glp-1 ] and glucose - dependent insulinotropic polypeptide [ gip ] ) . these hormones control blood glucose by increasing synthesis and release of insulin from pancreatic  cells in response to a meal . glp-1 also reduces hepatic gluconeogenesis by inhibiting the pancreatic  cells.9 sitagliptin is primarily excreted in the urine as the unchanged drug by renal tubular secretion . about 16% of the drug is excreted as its metabolites and primarily metabolized by cyp3a4 , cyp2c8 , and p - glycoprotein . sitagliptin is not an inhibitor of cyp isozymes 3a4 , 2c8 , 2c9 , 2d6 , 1a2 , 2c19 , or 2b6 . it is neither an inducer of cyp3a4 nor does it inhibit p - glycoprotein - mediated transport.10 a study by wilke et al11 showed that a nonsynonymous coding single - nucleotide polymorphism  rs4149056  in slco1b1 significantly increased the exposure to simvastatin and the risk of muscle toxicity . oatp1b1 , encoded by slco1b1 , facilitates the hepatic uptake of several endogenous compounds and statins . changes in the activity of this transporter can increase the severity of statin - related muscle damage . genetic variability in slco1b1 also alters plasma concentration of statins , although the overall pharmacokinetic profile of simvastatin appears to be altered more than that of any other drug in the class.12,13 pasanen et al14 demonstrated that homozygous carriers of the c allele at rs4149056 had a greater exposure to the active simvastatin acid than subjects homozygous for the ancestral t allele . the frequency of mylagias with atorvastatin was 2.7%8.4% vs 3.1% in patients receiving placebo and is one of the common reported skeletal muscle side effects seen with the use of atorvastatin ( lipitor).8 in contrast , a study by graham et al9 in 2004 reported an average incidence of 0.44 in 10,000 patients ( who developed rhabdomyolysis ) being treated with atorvastatin , simvastatin , or pravastatin , with a 95% confidence interval of 0.200.84 . these patients had been taking lipid - lowering agents alone or in combination.9 the fda reported a total of 601 cases of statin - associated rhabdomyolysis from november 1997 up till march 2000.15 the total case percentages associated with each statin were as follows : fluvastatin at 2% , lovastatin at 7% , pravastatin at 12% , atorvastatin at 12% , cerivastatin at 32% , and simvastatin at 36% . in a similar study by thompson et al,16 an expanded search was carried out to ensure compatibility with prior searches and 612 cases were identified for the same given period . the incidence of fatal rhabdomyolysis through may in 2001 had been estimated using information from the databases obtained from the fda and national prescription audit plus ( ims health , fairfield , ct , usa ) and found to be at only 0.15 deaths per one million prescriptions.17 the estimated incidences per one million prescriptions for various statins were as follows : cerivastatin at 3.16 , lovastatin at 0.19 , simvastatin at 0.12 , pravastatin and atorvastatin at 0.04 , and fluvastatin at zero.17 diltiazem is considered a weak inhibitor of the cyp3a4 isoenzyme and although our patient had been taking diltiazem ( 180 mg daily ) along with atorvastatin for several months , it would be an unlikely cause for this acute rhabdomyolysis episode . the patient developed rhabdomyolysis within a few days after sitagliptin was added to her continuing medical therapy , which included atorvastatin . she did not have any other known etiologies for developing rhabdomyolysis , leading to the conclusion that the drug interaction between atorvastatin and sitagliptin caused toxicity and rhabdomyolysis . medical literature review showed very limited case reports of potential interaction of sitagliptin with statins causing rhabdomyolysis.5,18 although sitagliptin has been reported to cause myalgias or arthralgias , it has not been reported to cause rhabdomyolysis on its own.5,1819 several drug interactions have been reported with statins in the past . to our knowledge , however , only one case has been reported on the interaction of sitagliptin with statins causing rhabdomyolysis , making this case an unusual presentation . a medication review should thoroughly be done in case of myalgias in the absence of any medical or traumatic event likely to cause muscle damage .