Evaluating the therapeutic impact of tirzepatide in people with partial lipodystrophy

In 40 people with partial lipodystrophy, tirzepatide use was associated with significant drops in body weight, HbA1c, triglycerides, and daily insulin needs over a median follow-up of about 9.5 months. The authors conclude that tirzepatide may be a useful option in this severe insulin-resistant condition, although the study was retrospective and uncontrolled.

Observational study — single-center retrospective observational study. Population: Patients with partial lipodystrophy treated with tirzepatide at a single center. Sample size: 40 patients. Follow-up: median 9.5 months follow-up. Interventions: tirzepatide.

Among the 40 patients, 65% had FPLD1-like, 10% FPLD2, 17.5% FPLD3, and the remainder other or unclassified subtypes. After a median follow-up of 9.5 months, median body weight decreased from 91.0 kg to 82.8 kg, HbA1c from 65 to 52 mmol/mol, triglycerides from 2.80 to 1.83 mmol/L, and daily insulin requirement from 177.5 IU to 58.0 IU. The authors report all four reductions were statistically significant.

Researchers studying tirzepatide will find this paper useful because it reports real-world retrospective data on tirzepatide in partial lipodystrophy, a rare condition with severe insulin resistance and few licensed options. It does not establish efficacy or safety in a controlled trial, and it does not address dosing, long-term outcomes, or whether benefits apply across all lipodystrophy subtypes.

Key findings

• Body weight fell from a median of 91.0 kg to 82.8 kg at a median follow-up of 9.5 months (P < .0001).
• HbA1c decreased from 65 mmol/mol to 52 mmol/mol (P < .0001).
• Serum triglycerides dropped from 2.80 mmol/L to 1.83 mmol/L (P = .0005).
• Daily insulin requirement fell from 177.5 IU to 58.0 IU (P = .0028).
• 40 patients were included, of whom 87.5% were female with a median age of 47 years.

Limitations

• Retrospective, single-center design with no control group limits causal inference.
• Observational treatment assignment leaves potential confounding by indication or concurrent treatment changes.
• Median follow-up of 9.5 months is short for a chronic metabolic disorder.
• Sample size is small and includes heterogeneous lipodystrophy subtypes.

The record

• Journal: The Journal of clinical endocrinology and metabolism 111(9): e2146-e2153
• Published: 2026-08-13
• PMID: 41866320 — DOI: 10.1210/clinem/dgag126
• MeSH terms: Humans, Insulin Resistance, Treatment Outcome, Retrospective Studies, Adult, Middle Aged, Female, Male, Lipodystrophy, Familial Partial, Tirzepatide
• Funding: Wellcome Trust; National Institute for Health Research (NIHR); Wellcome Trust; Cambridge Biomedical Research Centre; NIHR Rare Disease Translational Research Collaboration
• Author countries: UK

Peptide profiles: Tirzepatide.

All indexed evidence: Tirzepatide trials & papers.

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