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Assistant Professor, Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Clinical Pharmacy Specialist, Department of Integrated Health, Holston Medical Group, 105 West Stone Drive, Suite 5-D, Kingsport, Tennessee 37660, fax 423/857-2791, bgross{at}uthsc.edu
Associate Professor, Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Director of Pharmacotherapy Services, Department of Disease Management, Holston Medical Group
Assistant Professor, Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Clinical Pharmacy Specialist, Department of Disease Management, Holston Medical Group
Internal Medicine Group-La Jolla, University of California San Diego Medical Center
Published Online, January 26, 2010. www.theannals.com, DOI 10.1345/aph.1M323
Case Report. A 58-year-old male with a history of type 2 diabetes and nonalcoholic steatohepatitis (diagnosed in 2006) presented to the clinic for diabetes management. At the time, the patient's aspartate aminotransferase (AST) was 53 U/L (normal <40 U/L) and alanine aminotransferase (ALT) was 102 U/L (normal <40 U/L). The patient was started on rosuvastatin 10 mg once daily. Baseline total cholesterol was 146 mg/dL, triglycerides were 245 mg/dL, high-density lipoprotein cholesterol was 33 mg/dL, and low-density lipoprotein cholesterol was 75 mg/dL. One month following therapy, AST and ALT had declined to 35 U/L and 64 U/L, respectively.
Two months after the initiation of rosuvastatin, the patient was started on sitagliptin 100 mg once daily due to elevated hemoglobin A1C of 8.2%. The patient's other medications included amlodipine 5 mg once daily, benazepril 20 mg once daily, aspirin 81 mg once daily, glucosamine 500 mg once daily, chondroitin 400 mg once daily, and indomethacin 25 mg once daily as needed. One month after initiation of sitagliptin, liver enzymes were monitored and revealed an AST and ALT of 71 U/L and 127 U/L, respectively. Four days later the AST and ALT levels were 70 U/L and 137 U/L, respectively. All other corresponding hepatic function results were within normal range for the patient. A full medication review was performed. Sitagliptin was discussed as a possible cause of increased liver enzyme levels and promptly discontinued. Reexamination of liver enzymes a month after discontinuing sitagliptin revealed a significant decrease in AST and ALT (48 U/L and 90 U/L, respectively). Most recently, 6 months after discontinuation, AST and ALT were 35 U/L and 62 U/L, respectively.
Discussion. The efficacy and safety of sitagliptin have been well documented in clinical trials of patients with type 2 diabetes, either as monotherapy or in combination with other oral hypoglycemic agents.1-5 Raz et al. examined the safety and efficacy of sitagliptin as monotherapy at 100-mg and 200-mg doses versus placebo. The researchers found no mean change from baseline in AST or ALT between treatment groups.1
The effect of sitagliptin in combination with metformin has also been studied.3-5 Charbonnel et al. examined the efficacy and safety of sitagliptin 100 mg versus placebo added to ongoing metformin therapy. They found no difference between treatment groups in the occurrence of elevations of AST or ALT.3 Nauck et al. conducted a study in which patients received either sitagliptin 100 mg and metformin, or glipizide and metformin. The researchers found a slight mean decrease in ALT in the sitagliptin group versus a slight increase in ALT in the glipizide group, which was not statistically significant.5
Although no significant elevation of hepatic enzymes has been reported in the literature, most of the trials involving the safety of sitagliptin were small and short in duration. Monitoring hepatic function in individuals with a history of nonalcoholic steatohepatitis or elevated hepatic enzymes may need to be considered in patients initiated on sitagliptin.
Footnotes
Financial disclosure: None reported
References
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