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.