Lipolysis Agents for Non-Submental Fat Reduction

Goals/Purpose: With an ever-growing population qualifying as overweight or obese, the desire for correction of localized fat deposits is significant. Injectable lipolytic agents are gaining popularity as an alternative fat removal strategy to liposuction, foregoing an invasive procedure with its associated risks, reducing pain and patient discomfort, virtually eliminating recovery time, and lowering cost burden. Deoxycholic acid (DCA), the only lipolytic agent approved for cosmetic use in the US, received FDA approval in 2015 for the treatment of redundant submental fat (SMF). Phosphatidylcholine (PC) is a second injectable agent globally recognized for the elimination of body fat deposits, though not currently FDA-approved for cosmetic lipolysis. Multiple randomized controlled trials demonstrate lipolytic agent efficacy in SMF reduction. Herein, we present a systematic review of efficacy and safety outcomes from injectable lipolytic agents in non-SMF regions, where existing literature is more limited.

Methods/Technique: Scopus, Embase, and MEDLINE through August 1, 2024 with predefined search terms and inclusion/exclusion criteria, in accordance with PRISMA methodology. Studies that reported localized, non-submental fat reduction via lipolysis agents were included through screening by two independent reviewers.Studies that mentioned localized fat reduction using invasive techniques were excluded.

Results/Complications: A total of 25 studies published between 2005 and 2023 were included after screening 4,702 records. Study methodologies included clinical trials and randomized controlled trials (n = 6, 24%) and retrospective, prospective studies, case series, or case reports (n = 19, 76%). A total of 3,178 patients were treated with injectable lipolysis agents, with ages ranging from 18 to 83 years and BMI from 18.5 to 49.8 kg/m². The majority of patients were female (79.5%). Most studies (n = 18, 72%) focused on nonpathological localized adiposity, while others addressed lipomas, Dercum disease, or lipohypertrophy (n = 7, 28%). Deoxycholate/deoxycholic acid (DCA) (n = 16, 64%) and phosphatidylcholine-deoxycholate (PTC-DCA) (n = 6, 24%) were the most studied agents. Additional agents included phosphatidylcholine (PC), ascorbic acid/ascorbyl-palmitate (AA-AP), CBL-514, caffeine-hyaluronic acid (C-HA), and organic silicium (OS). The most commonly studied treatment areas included the abdomen (n = 13, 52%), arms (n = 7, 28%), thighs (n = 7, 28%), knees (n = 6, 24%), chest (n = 5, 20%), back (n = 5, 20%), flanks (n = 4, 16%), and hips (n = 3, 12%). Follow-up across all studies ranged from 4 weeks to 20 weeks following final treatment. Adipose reduction was reported in 93.75% of studies (n = 15), with 37.5% (n = 6) demonstrating statistically significant results. DCA, PTC-DCA, AA-AP, CBL-514, C-HA, and OS were associated with significant localized adipose reductions. Studies evaluating lipomas and Decrums disease showed a 75% average reduction in lipoma size, although recurrence was observed in one case. Patient satisfaction, assessed in 24% of studies (n = 6), ranged from 57.1% to 86%. Adverse events were reported in 96% of studies (n = 24), with edema (n = 17, 70.8%), pain (n = 11, 45.8%), erythema (n = 11, 45.8%), bruising (n = 9, 37.5%), subcutaneous nodules (n = 7, 29.1%), and numbness (n = 7, 29.1%) being most frequent. Less frequent events included pruritis (n = 3, 12.5%), skin necrosis (n = 3, 12.5%), paresis (n = 1, 4.2%), diarrhea (n = 1, 4.2%), and menstrual irregularities (n = 1, 4.2%).

Conclusion: While popularized submental fat reduction, injectable lipolysis agents have proved useful for localized fat reduction in the abdomen, arms, thighs, knees, chest, back, flanks, and hips. In addition to the commonly used DCA (kybella), other injectable agents such as phosphatidylcholine, ascorbic acid, and caffeine-hyaluronic acid have promising results. We have shown additional agents that can be added to the armamentarium of localized, non-invasive fat reduction in both aesthetic and pathologic cases.