Tirzepatide for Lipodystrophy

Abstract Background Lipodystrophy encompasses a group of rare disorders associated with severe metabolic disease. These disorders are defined by abnormal fat distribution, with near-total (generalized lipodystrophy, GL) or partial (partial lipodystrophy, PL; i.e. familial partial lipodystrophy, FPLD) absence of adipocyte mass leading to a decreased ability to store lipids safely. Excess lipids are more likely to be stored in non-adipose tissues, which leads to the metabolic manifestations. We have recently shown that glucagon-like peptide-1 agonists are associated with metabolic improvements in FPLD. We hypothesized that tirzepatide, a dual incretin, may also lead to metabolic improvement in patients with lipodystrophy. Methods Observational cohort of patients with PL or GL who received tirzepatide clinically were tracked in the context of ongoing natural history studies. Results Seventeen patients received tirzepatide, 14 with FPLD (ages within 30-74 years; 12 female 2 male). After a median 8.7 months of follow-up, BMI (medianΔ -1.7; range -5.9 to 0.9 kg/m 2 ; p =0.008), HbA1c (medianΔ -1.1%; range -6.3 to -0.1%; p 20.9; 26.2->25.4; 19.5->17.6 kg/m 2 ), HbA1c (8.5%->7.0%; 10.2%->7.8%; 9.1%->6.5%), triglycerides (91->80; 641->293; 1238->100 mg/dL or 1.03->0.90; 7.24->3.31; 14.0->1.13 mmol/L), and total daily insulin requirement (85->0; 0->0; 1000->750 units/day). Three patients did not tolerate dose escalation due to gastroesophageal reflux. Conclusions Tirzepatide may be an effective treatment for patients with lipodystrophy.