Lipolysis innovations target demand for noninvasive fat reduction

Key Points

Las Vegas - Body contouring is the next aesthetic frontier, and thanks to advances in noninvasive lipolysis, the future is very bright, says Mark S. Nestor, M.D., Ph.D.

Speaking at the 30th annual Fall Clinical Dermatology Conference, Dr. Nestor reviewed new and investigational technologies for removing fat, including cryolipolysis, high-intensity focused ultrasound (HIFU), mesotherapy and low-level laser therapy (LLLT).

"There is great demand for effective procedures that can reduce or remove unwanted fat with less morbidity than liposuction," says Dr. Nestor, voluntary associate professor, department of dermatology and cutaneous surgery, University of Miami Miller School of Medicine. "We are seeing an expanding array of modalities that may be used alone for specific indications or in combination to meet the need for noninvasive body contouring, and there is also evidence, at least for LLLT, that the treatment may have implications for improving overall health."

A cryolipolysis platform for noninvasive body contouring received clearance from the Food and Drug Administration in September 2010 (CoolSculpting, Zeltiq). The treatment is delivered with a cooling applicator applied to the surface of the skin and is based on the principle that apoptosis of fat cells can be induced at a higher temperature than that causing apoptosis of skin, muscle or nerve cells. Cell contents released from the adipocytes after apoptosis, along with the cellular debris, are removed by infiltrating macrophages. Clinical studies show visible reduction in the fat layer occurs after a period of two to four months.

"Cryolipolysis causes minimum discomfort and the treatment is easy, but it takes 60 minutes per treatment area. Although it can be boring, patient acceptance is very good because it is relatively painless, well-tolerated, results in no downtime, and can produce consistent results for area treatments," Dr. Nestor says.

Ultrasound approach

An HIFU platform received FDA clearance in September 2011 for noninvasive reduction of waist circumference (Liposonix, Solta Medical). This procedure causes thermal coagulation of fat within the focal beam at precise tissue depths without causing harm to overlying skin or underlying structures.

As with cryolipolysis, the lipids released from the damaged adipocytes, along with the cellular debris, are removed via host inflammatory response mechanisms.

Data on file from a European study enrolling 104 patients treated for abdominal fat with the HIFU platform showed an average reduction in waist circumference of 2.5 cm at 12 weeks following a single session with a range up to 8 cm, Dr. Nestor says.

Mesotherapy

The injectable adipolytic agent ATX-101 (Kythera) is currently being investigated in premarketing clinical trials. A phase 2B double-blind, 10-center study randomized 129 patients to receive a series of six injections with placebo or ATX-101 1 mg/cm² or 2 mg/cm² into the submental region. Injections were repeated every four weeks, and efficacy was assessed prior to each injection and at weeks 24 and 32 (four and 12 weeks after the last treatment).

Physician assessments showed continued improvement in the 2 mg treatment group through week 24 with maintenance of the benefit at week 32, which was the primary endpoint. There were statistically significant differences favoring the 2 mg dose compared with placebo at all visits beginning at week 12, as well as in reduction in MRI-measured submental fat volume compared with placebo at week 32.

There was also a statistically significant benefit for the 1 mg dose compared with placebo at week 32 in the objective assessment, while about 85 percent of patients in both ATX-101 groups were satisfied with the treatment. Adverse events associated with ATX-101 were limited to injection site reactions and included some reports of numbness and pain, but they were all mild.

"With its ease of use, this injectable therapy should be a wonderful modality for targeted fat reduction, particularly in the submental region. The phase 2B study showed that, as expected, the treatment did not cause a reduction in skin laxity, and so it may be less useful as a single modality for treating older patients where skin tightening will also be important," Dr. Nestor says.