TOPLINE:

In patients with partial lipodystrophy (PLD), treatment with tirzepatide — a dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonist — was associated with significant reductions in body weight; A1c, serum triglyceride, and alanine aminotransferase levels; and daily insulin requirements.

METHODOLOGY:

• Researchers conducted a single-centre retrospective observational study to evaluate the effect of tirzepatide on metabolic outcomes in patients with PLD.
• They included 40 patients with PLD (median age, 46.5 years; 87.5% women) who were initiated on 2.5 mg tirzepatide weekly, with non-standardised dose escalation up to a maximum of 15 mg.
• Changes from baseline to a median follow‑up of 9.5 months were evaluated for body weight; BMI; A1c, serum triglyceride, and liver enzyme levels; and daily insulin requirements.

TAKEAWAY:

• After treatment with tirzepatide, the median body weight reduced significantly from 91.0 to 82.8 kg, corresponding to a median total body weight loss percentage of 7.9%; the median BMI declined from 31.5 to 27.7 (P < .0001 for both).
• Median A1c levels decreased significantly from 65 to 52 mmol/mol (P < .0001), and median serum triglyceride levels declined from 2.80 to 1.83 mmol/L (P < .0005).
• Median daily insulin requirements reduced from 177.5 to 58.0 IU/24 hours (P = .0028). Following treatment with tirzepatide, 12 (36.4%) out of 33 (82.5%) patients with baseline A1c levels above the diabetic threshold (> 48 mmol/mol) achieved A1c levels below this threshold despite reductions in insulin use.
• Median serum alanine aminotransferase levels fell significantly from 39 to 32 U/L (P = .01). No significant reduction in aspartate aminotransferase levels was observed.

IN PRACTICE:

"Our study suggests that in people with PLD, treatment with tirzepatide may provide substantial metabolic benefits for the treatment of diabetes and hypertriglyceridemia," the authors wrote.

SOURCE:

This study was led by Mandour O. Mandour, MBBS, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, England. It was published online on March 20, 2026, in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The relatively small sample size limited statistical power. Data on adverse events were captured for only 70% of the study population, potentially introducing reporting bias. As a retrospective study relying on previously collected clinical data, there may have been information bias due to incomplete data.

DISCLOSURES:

One author reported receiving support from the Wellcome Trust, and another reported receiving support from the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre and NIHR Rare Disease Translational Research Collaboration. One author declared serving as a speaker and attending an advisory board for Chiesi.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.