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.