Case Presentation: A 49-year-old male presented from his PCP office with a ten-day history of diarrhea, 20-pound weight loss, and severe hypotension. His history included Type II Diabetes Mellitus controlled with tirzepatide 2.5mg weekly injection, hypertension on 40 mg lisinopril, obesity class III, obstructive sleep apnea, and gout on daily allopurinol. He was originally prescribed oral semaglutide however weight loss did not occur, and he was transitioned to tirzepatide eight months before this admission. Three months after starting tirzepatide he developed diarrhea, and the dose was reduced with initial improvement in his side effects. However, significant diarrhea recurred five months later, resulting in this admission. In the ED, a physical exam revealed a well-developed male with dry mucous membranes, heart rate 93, blood pressure of 69/44mmHg, and respirations 16, breathing 97% on room air. Lab work revealed pH 7.12, base excess –15.4, bicarbonate 13.7mmol/L, sodium 127 mmol/L, blood urea nitrogen >120 mg/dL, creatinine (Scr) 10.96 mg/dL [baseline 1.15mg/dL], non-anion gap acidosis of 8.8, lipase 262 U/L, mild leukocytosis 13,000 with left shift, normal lactic acid, and A1c 6%. Computed tomography of the abdomen and pelvis without contrast was negative for acute inflammatory process. He was treated with intravenous fluids, norepinephrine drip, and empiric piperacillin-tazobactam, and transferred to our tertiary care center with non-oliguric acute kidney injury (AKI) and hypovolemic shock. Nephrology consultants initiated bicarbonate infusion with a goal bicarbonate level above 20. His urine sodium was 39, and urinalysis was unremarkable. At 48 hours, the serum creatinine was 1.83mg/dL and the patient requested discharge home. He was discharged on no medications. Two weeks post-hospitalization, repeat serum creatinine was normal and both lisinopril and allopurinol were resumed at 4 weeks. His hemoglobin A1c was 6.0% and diabetes medications were not restarted.
Discussion: In 2022, the FDA approved tirzepatide for the treatment of type two diabetes. This drug was the first glucose-dependent insulinotropic polypeptide (GIP) combined with glucagon-like peptide-1 (GLP-1) receptor agonists to show efficacy in A1c reduction and weight loss. However, there is a 10% risk of gastrointestinal side effects that can result in life-threatening complications such as acute renal failure. According to the SURPASS 1-5 trials, gastrointestinal side effects, most commonly nausea, vomiting, and diarrhea, typically occur with dose titration of GLP-1 agonists but improve with time and are usually transient. Only 6% of patients studied required treatment discontinuation for side effects. Our patient had recurrent diarrhea episodes despite dose reduction and ultimately required treatment cessation. Less than a dozen case reports have detailed this complication. Combination ace-inhibitor use combined with volume loss likely precipitated progression to non-oliguric prerenal acute kidney injury in our patient.
Conclusions: GLP1 receptor agonists are among the most popular pharmaceuticals with a flourishing landscape of trial data that is ongoing. Despite robust trials detailing safety profiles, patients must be counseled on potential serious complications that may occur and prohibit use.