A Multimodal Intervention Including Tirzepatide in Women with Lipedema and Excess Body Weight: A Pilot Case Series

Background: Lipedema is a chronic adipose tissue disorder characterized by disproportionate lower-limb fat accumulation, pain, and resistance to conventional weight-loss strategies. Tirzepatide produces substantial weight loss, but evidence in lipedema is limited. Methods: This single-center ambispective pilot case series described a 22–25-week routine clinical course in 2025. During the first 8–9 weeks, all participants received only a low-carbohydrate Mediterranean diet and recommendations for aerobic and resistance exercise; no participant received tirzepatide during this phase. After completion of the 8–9-week non-pharmacological phase, four participants started tirzepatide (2.5–7.5 mg once weekly) and continued it for the remaining 14–16 weeks, whereas one participant declined pharmacotherapy. After approval by the Bioethics Committee (Resolution No. 12/2026, 4 February 2026), the 2025 data were analyzed retrospectively; participants gave verbal consent to further follow-up in March–April 2026 and were followed up prospectively, and all signed written consent for publication of their data and photographs in October 2026. Anthropometric, ultrasound, biochemical, pain, and quality-of-life outcomes were summarized descriptively for each case. Where available, changes are reported separately for the diet-and-exercise phase (T1–T2) and the tirzepatide phase (T2–T3). Results: Weight loss among the five completers ranged from 7.7 to 17.1 kg. Body fat percentage decreased in four of five participants, whereas skeletal muscle mass decreased numerically in all four tirzepatide-treated participants. Lower-limb circumferences and subcutaneous adipose tissue thickness generally decreased, although the magnitude and distribution of changes differed between participants. Fasting glucose and HOMA-IR decreased in most cases, whereas lipid changes were mixed. Patient-reported SF-36 scores (assessed only at T2 and T3) generally improved among the four participants receiving tirzepatide, particularly for bodily pain, while pressure pain threshold responses (T2 to T3) were heterogeneous. No adverse events, gastrointestinal symptoms, dose reductions, treatment interruptions, discontinuations, or serious adverse events were reported by the four tirzepatide-treated participants; the study was not designed to assess safety. Conclusions: This ambispective pilot case series provides preliminary, hypothesis-generating observations on a multimodal intervention that included tirzepatide in four of five women with lipedema and excess body weight. The observed changes cannot be attributed to tirzepatide or interpreted as a lipedema-specific effect because all participants received concurrent dietary, exercise, and supplementation interventions, and the participant who declined pharmacotherapy was not a comparator or control.