Metabolic Improvements With Tirzepatide in Lipodystrophy: A Novel Option?

Abstract

OBJECTIVE 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]; e.g. 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 nonadipose tissues, which leads to the metabolic manifestations. We have recently shown that glucagon-like peptide-1 agonists are associated with metabolic improvements in FPLD. Here, we hypothesize that tirzepatide, a dual incretin, may also lead to metabolic improvement in patients with lipodystrophy. RESEARCH DESIGN AND METHODS An observational cohort of patients with lipodystrophy who received tirzepatide clinically were tracked in the context of ongoing natural history studies. RESULTS Seventeen patients received tirzepatide, 14 who had FPLD (aged 30–74 years; n = 12 female and 2 male). After a median 8.7 months of follow-up, the following were significantly reduced: BMI (median difference, −1.7; range, −5.9 to 0.9 kg/m2; P = 0.008), HbA1c (median difference, −1.1%; range −6.3% to −0.1%; P < 0.001), triglycerides (median difference, −65 mg/dL [−0.73 mmol/L]; range, −3,820 to 43 mg/dL [−43.2 to 0.49 mmol/L]; P = 0.003), and total daily insulin requirements (median difference, −109; range, −315 to 0 units/day; P = 0.002). Three additional patients with rarer forms of lipodystrophy, also with robust response to tirzepatide, are also discussed (atypical PL, n = 1; acquired GL; n = 2; aged 35–64 years; all female). Side effects were limited to benign gastrointestinal symptoms. CONCLUSIONS Tirzepatide may be an effective treatment for patients with lipodystrophy.