7098 Paradoxical Worsening of Dyslipidemia with Tirzepatide

Abstract Disclosure: J.E. Pruett: None. B. Carranza Leon: None. Background: While weight loss typically is associated with improvement in dyslipidemia (DLD), certain instances of extreme weight loss have been implicated in paradoxical worsening of DLD. For example, underweight women with anorexia nervosa have higher serum low-density lipoprotein cholesterol (LDL-C) than normal weight healthy counterparts (1). However, this has yet to be shown with dual incretin receptor agonist therapies such as tirzepatide. Clinical Case: A 75-year-old female with dyslipidemia treated with evolocumab (LDL-C 183 mg/dLbefore treatment), type 2 diabetes mellitus, and class 1 obesity was switched from glimepiride to tirzepatide in an effort to address the above conditions. Over the span of 6 months, tirzepatide was uptitrated to 15 mg, and the patient lost over 70 pounds with hemoglobin A1c decreasing to 5.8%. However, LDL-C more than doubled from 155 to 342, with high-density lipoprotein cholesterol (HDL-C) dropping from 57 to 42. Interestingly, triglycerides stayed the same from 124 to 122 during this timeframe. Out of concern for inefficacy of evolocumab, she was switched to inclisiran. Two months later, LDL-C was even higher at 360 with unchanged HDL-C and a moderate increase in triglycerides to 154. Given prior case reports of extreme weight loss worsening DLD along with the LDL-C skyrocketing upon tirzepatide initiation, the decision was made to decrease tirzepatide from 15 mg to 5 mg. Within the next three months, though her weight only changed by one pound, her LDL-C subsequently dropped to 114, HDL-C rose to 65, and triglycerides dropped to 71. Conclusion: To our knowledge, this is the first case report linking dual incretin receptor agonist therapy with worsening dyslipidemia. Reference: (1) Weinbrenner, T.; Züger, M; Jacoby, G.E; et al. Lipoprotein metabolism in patients with anorexia nervosa: a case-control study investigating the mechanisms leading to hypercholesterolaemia. British Journal of Nutrition. 2004;91:959-969. Presentation: 6/3/2024