Evaluating the therapeutic impact of tirzepatide in people with partial lipodystrophy

Background: Lipodystrophy syndromes (LD) are a group of rare conditions characterised by the generalised or partial absence and/or dysfunction of adipocytes. Due to the lack of fat storage capacity, excess lipid accumulates in other tissues, leading to severe insulin resistance. At present, effective therapeutic options remain limited, with metreleptin currently the only specific licensed treatment. To this end, we evaluated the therapeutic impact of tirzepatide in people with partial lipodystrophy (PLD). Methods This was a single-centre, retrospective, observational study, including all patients with PLD treated with tirzepatide between January 2022 and September 2025. Results 40 patients with PLD were included (FPLD1 like =26 (65%), FPLD2 =4 (10%), FPLD3 =7 (17.5%), FPLD7=1 (2.5%), APLD=1 (2.5%), Unclassified=1 (2.5%)). 87.5% (n=35) were female with a median age of 47 years (IQR 39 - 59) and a median BMI of 31.5 kg/m2 (IQR 27.3 - 35.5). After a median 9.5 month follow-up (IQR 7 - 11), marked reductions were seen in body weight from 91.0kg (IQR 75.0 - 106.0) to 82.8kg (IQR 69.0 - 93.4; p<0.0001), in HbA1c from 65 mmol/mol (IQR 54.5 - 85) to 52 mmol/mol (IQR 39 - 62; p<0.0001) and in serum triglycerides from 2.80 mmol/L (IQR 1.6 - 3.7) to 1.83 mmol/L (IQR 1.0 - 2.9; P=0.0005). Daily insulin requirements fell from 177.5 IU (IQR 101.3 - 213.8) to 58.0 IU (IQR 0 - 112.5; P=0.0028). Conclusion In patients with partial lipodystrophy, tirzepatide use resulted in substantial statistically significant reductions in weight, glycaemic control, serum triglycerides and daily insulin requirement. We recommend further prospective studies to support these findings and to evaluate its impact earlier in the course of the disorder.