Christopher N. Nguyen, MD, and Michael Gold, MD, review the evidence and provide their clinical  experience working with four popular modalities for fat reduction

Fat reduction has become a cosmetic and medical priority for many patients over the past decade, particularly considering the obesity epidemic and increasing focus on weight loss in pop culture. In a 2019 survey, more than 80% of Americans reported that they were bothered by excess weight on their body1. The study also found that body contouring was the most frequently sought-after cosmetic procedure. For decades, liposuction has been the only available method to reduce localised adipose tissue. While effective, this approach is invasive, has limitations, and, as with any surgery, poses multiple risks2

More recently, non-invasive fat reduction options have surfaced as an exciting alternative to liposuction. Compared to surgical fat removal, non-invasive options offer a lower cost, preferable safety profile, and speedier recovery2. Because of this, non-invasive fat reduction has exploded in popularity, becoming one of the fastest-growing areas of aesthetic medicine. The American Society for Dermatologic Surgery reported over 1 million body contouring procedures in 2019, compared to less than 150,000 in 2012, representing an over 5-fold increase3. More specifically, non-invasive fat reduction procedures increased by 58% in 2021 from 2020, even in the midst of the COVID-19 pandemic4. In total, the market size in 2021 for non-invasive fat reduction globally was estimated at over 1 billion US dollars and is projected to experience a compound annual growth rate of 16.1% from 2022 to 2030, in part due to the population’s increased disposable income and awareness of procedures5

The premise of nonsurgical fat reduction lies in using cooling or heating technology to induce fat cell destruction. A variety of modalities have been FDA-approved for these purposes and can be separated into four primary techniques: 

  • Cryolipolysis, 
  • Radiofrequency (RF), 
  • Lasers, and 
  • Ultrasound. 

Each technology has witnessed expansion in the last decade5. The objective of this article is to provide an update on each of these non-invasive fat reduction modalities, focusing on studies performed in the last few years, as well as offer our analyses of the field.


The use of non-invasive freezing for fat reduction was first studied in pigs in 20076. Since then, it has been validated in humans in numerous studies7. Of the four modalities, cryolipolysis — cold-induced fat reduction — is the only one that involves cooling. In the US, the procedure is commonly referred to as CoolSculpting® (Zeltiq Aesthetics, Pleasanton, CA) and was FDA-approved in 20108,9.

In 2017, Zeltiq was acquired by Allergan Aesthetics, an AbbVie Company. In 2019, cryolipolysis was the most performed body sculpting procedure, with 257,000 procedures performed in the US alone3. In total, over 4 million cryolipolysis procedures have been performed worldwide10

The precise mechanism is not fully understood but generally entails suctioning of tissue combined with cold temperature (<10°C) application, thereby inducing apoptosis of adipocytes. Scientists have found adipocytes to be more susceptible to cold-induced injury due to their lipid-rich state compared to other cells, which are water-rich. Because the crystallisation of lipids occurs at higher temperatures than the freezing point of water, adipocytes are affected while other cells remain stable8. Following adipocyte apoptosis, cells are gradually cleared by inflammation and macrophages, peaking at around 4 weeks and ending by 12 weeks post-treatment6.

In a systematic review of over 1500 patients, all 19 included studies reported significant fat reductions with cryolipolysis in multiple body areas, ranging from 10.3% to 28.5%7. Currently, very few studies have examined the long-term durability of results; however, Bernstein reported persistent and visible fat reduction at 6- and 9-years post-treatment9

Over the past several years, new applicators and software systems have been launched aimed at optimising the patient experience and achieving better results. The CoolMini™ is a compact applicator designed to treat smaller areas of fat and demonstrated a mean reduction of 22.30cm3 (P<0.0001) in the submental area11. On the other hand, the CoolAdvantage® applicators have a contoured design with a larger surface area to allow for increased patient comfort with shorter treatment times when covering larger areas. A multinational prospective study endorsed higher patient satisfaction with these newer applicators and found that 89.6% of 112 patients were ‘satisfied’ or ‘very satisfied’12. High rates of satisfaction were found among a diverse patient population independent of body area, number of cycles, and body mass index (BMI). Additionally, the most recent CoolSculpting system, CoolSculpting Elite, was released in 2020 that can deliver two treatments simultaneously. The removable applicators are available in a range of shapes and sizes to accommodate various amounts, locations, and textures of fat. Of note, the novel C-shaped cup redesign of the applicator is better able to conform to natural body curvatures and has demonstrated improved vacuum seal, volume of tissue drawn, and tissue contact, along with reduced patient pain13

Lastly, new clinical and histological evidence suggests that CoolSculpting triggers dermal remodelling and helps tighten skin as well14

Other countries have also developed their own cryolipolysis devices with features and efficacy like that of the US. The French cryolipolysis device Cristal® (Deleo, Saint Raphael, France) demonstrated a mean fat reduction of 2.8cm (P<0.05)15. Meanwhile, Spain developed and validated the Cooltech system (Sinclair Pharma, London, UK) that cools to -8°C and has the ability to treat multiple areas simultaneously. Studies found average reductions of 19.6% (P=0.001) in the abdominal area, 15.34% in the infraumbilical area, 11.03% in the right flank, and 4.57% in the left flank16,17.

Furthermore, in 2019, Marmol et al. investigated the benefits of a newer model (CoolTech Define, Sinclair Pharma, London, UK)18. The updated model provided several advantages: it utilised a cooler temperature of -10°C, as well as 360° complete cooling. In addition, the newer model used a shallower applicator cavity depth, two additional applicators, and increased diversity in applicator shapes and sizes. The newer model provided faster (36% quicker) and more homogenous cooling. The average skinfold change was -7.80 mm (P=1.62×10-28), while the average circumference change was -32.3 mm (P=2.20×10-22). Thus, superior results were achieved while lower temperatures allowed for less treatment time and greater patient comfort. The most recent investigation to optimise this system investigated ischemia produced by the vacuum suction of applicators which affects the biological heat in the tissue19. Investigators were able to develop an accurate mathematical model that determines the blood flow in a treated tissue based on the applicator’s shape and size. This model has been strongly correlated with human studies and is useful for predicting and optimising the efficacy and safety of different applicators19.

In 2017, the Korean FDA approved their own device, Cryo-Elsa (Huons Co. Ltd., Seongnam, Korea), and similarly found significant reductions in waist circumference (4.1 cm [P=0.023]) and abdominal subcutaneous fat (4.8 cm2 [P=0.182]). Interestingly, the Lee et al. study was the first to document visceral fat reduction (16.2cm2 [P=0.023]) from cryolipolysis8. A later split-body clinical trial in 2020 found the cross-sectional area of visceral adipose tissue in the treated abdomen decreased by 15.6% (P=0.003), while the untreated abdomen demonstrated no significant changes20

Visceral obesity has been strongly associated with metabolic disorders such as diabetes mellitus and coronary heart disease, with significant implications in morbidity and mortality8. So, while cryolipolysis has historically been a cosmetic procedure focusing on the removal of subcutaneous fat, these recent findings suggest visceral fat reduction may be possible as well. 

In the above studies and in a systematic review including over 3300 patients, most adverse events (AEs) following cryolipolysis were mild and transient, with erythema, paresthesia, bruising, and oedema composing the most common AEs10. Other serious AEs were rare and isolated events. Sharply demarcated areas with indented or ‘shark bite’ appearances have been occasionally described13. Thus far, histological studies have shown no long-term changes in nerve structure or function, and there have been no reports of permanent nerve damage2,7,10. The vacuum pressure may, in theory, cause complications to pre-existing hernias, but so far there have been no induced hernias in clinical studies7,10. Paradoxical adipose hyperplasia (PAH) is a rare but serious AE characterised by hardened adipose tissue at the treatment site months following the procedure. The incident rate for PAH appears to be lower for newer applicators compared to older models, however, demonstrating an over 75% decrease21. No significant changes in serum lipid levels or liver function tests have been documented7


Radiofrequency (RF) technology was initially introduced to treat skin laxity and wrinkles but has expanded to treat cellulite and fat reduction. In 2019, it was reported as the second most frequently used non-invasive fat reduction procedure, with 208,000 treatments performed3.

In contrast to cryolipolysis, RF relies on heat technology. Radiofrequency is electromagnetic energy, generally ranging in frequency from 3 KHz to 2 MHz, with lower frequencies reaching as far as 1.5 cm into the subcutaneous layer22.

Radiofrequency energy induces adipose tissue to generate heat by forcing collisions between charged molecules and ions23. Because adipose cells naturally have high-tissue resistance and low-heat transfer capabilities, heat dispersion is localised, which causes selective apoptosis of adipocytes and minimal risk to the epidermal and dermal layers23,24. Following treatment, peak inflammation and necrosis are seen histologically as far as 90 days post-treatment23

Since its advent, there have been numerous RF devices introduced to the market, most of which can be categorised as either monopolar, unipolar, or multipolar based on the number of electrodes they contain25. One example of a monopolar device is the truSculpt® ID (Cutera, Brisbane, CA). The device is hands-free and utilises short treatment times (15 minutes) without downtime. It can be used to treat a variety of body parts, including multiple areas simultaneously, and can treat areas of skin laxity and those covered by tattoos as well. This device also uses continuous real-time monitoring that maintains skin temperature at 43°C and subcutaneous tissue temperature at least 3–4°C higher to provide consistent results, as well as ensure safety26

Another monopolar RF device is the Exilis Ultra 360™ (BTL Industries, Marlborough, MA), the most recent iteration of Exilis devices. Chilukuri et al. demonstrated efficacy in fat reduction in a variety of body areas with high patient satisfaction and comfort (4.1/5) using combined Exilis monopolar RF and ultrasound technologies in 34 subjects27. This system also houses real-time temperature monitoring and a variety of applicators allowing for the treatment of a wide range of body areas25.

The Accent RF System (Alma Lasers, Caesarea, Israel) is a unipolar RF device that has demonstrated average fat reductions of 2.64 mm in the thigh and 1.8 mm in the buttocks in a study of 26 females28.

The Accent Prime™ is the latest system combining both unipolar RF technology and ultrasound technology. Kapoor et al. studied 255 patients after three treatment sessions with this system and reported an average reduction of 7.7–8.0 cm in abdominal circumference and a reduction of 2.86–3.18 cm in the thighs (P≤0.0001)22

Other modern platforms are multifunctional and not only perform lipolysis, but other non-invasive body contouring capabilities as well, such as muscle toning, skin surface remodelling, and cellulite reduction. One example of this is the Venus Bliss™ (Venus Concept, Toronto, Canada), which uses both multipolar RF and pulsed electromagnetic field technology29. Advantages of this treatment include a short therapy time (15–20 minutes), the ability to deliver energy to a depth of 4.5 cm, and uniform thermal energy distribution, which also induces collagen production and restructuring in the dermis and hypodermis. This system also features VariPulse™ technology that increases blood flow, enhances lymphatic drainage, and optimises patient comfort25. Similarly, the Evolve Trim (InMode, Irvine, CA) is another platform based on RF technology. The hands-free belt design and variety of applicators in this system allow for multiple areas to be treated simultaneously while ensuring homogenous energy distribution.

The most common AEs seen with RF devices are transient erythema, pain, and oedema. However, overall, this technology has shown to be very well-tolerated with minimal to no AEs2. Rarely, burns and blisters are seen, but these are generally due to operator error with real-time monitoring software and homogenous energy distribution helping to reduce discomfort and/or burns23


In 2019 alone, there were 48,000 laser lipolysis treatments performed, with numbers increasing by over 600% in the last decade3. In general, there are two types of lasers used for non-invasive fat reduction. The first iteration, low-level laser therapy (LLLT), was FDA-approved for fat reduction in 201030. An older laser technology, LLLT uses a 635 nm wavelength and, rather than raising the temperature of the tissue, creates pores in the adipocyte cell membrane, allowing for lipid leakage. This causes near-immediate emptying of adipocytes, resulting in a reduction in cell size with maximal effects immediately post-treatment. However, since there is no cell death, some argue this is the reason for diminishing results in the months post-treatment and eventual fat recurrence, in contrast to other modalities that cause adipocyte apoptosis and/or necrosis2.

Newer generation 1060 nm hyperthermic lasers were FDA-approved for non-invasive fat reduction in 201531. This specific wavelength penetrates to the depth of the subcutaneous tissue and is preferentially absorbed by adipocytes, heating cells to a controlled temperature between 42–47°C and sparing the overlying skin, dermis, and other surrounding cells. Because it does not target melanocytes, it can treat all skin types. Exposure to heat over tens of minutes damages the cell’s structural integrity. Over the next few months, the injured fat cells and cell debris are permanently removed by macrophages. Histologic studies have confirmed these findings, with inflammation gradually progressing up to a month after the treatment and lasting up to 6 months after treatment. The 1060 nm laser device has demonstrated equivalent reductions in fat thickness as compared to cryolipolysis32

The SculpSure® device (Cynosure, Westford, MA) has been approved for the abdomen, flanks, back, inner thigh, outer thigh, and, most recently, the submental area. The hands-free device allows for treatment of up to four sites at one time with a customisable applicator. 

Advantages of SculpSure include fast treatment time (25 minutes), no downtime, a cooling apparatus that maintains skin temperature at 15°C to prevent damage, and a uniform distribution of heat with no ‘hot spots.’ The efficacy of SculpSure in the flank was demonstrated in a prospective study of 49 patients showing an average fat reduction of 13% (p<.001), 96% patient satisfaction, and an average discomfort of 4/1033,34. Similar results have been demonstrated on the abdomen, thighs, and back35. Six-month follow-up showed persistent fat reduction as well36. SculpSure’s utility in the submental area was validated in a recent multi-centre study of 58 patients, demonstrating a 23% reduction in fat thickness with 91% patient satisfaction and an average treatment pain of 3.4/1037.

Another device, Venus Bliss™ (Venus Concept, Toronto, Canada), utilises a 1064 nm diode laser for lipolysis. Similar to SculpSure, Venus Bliss has a 25-minute treatment time, intended to be used every 4–6 weeks for 1–3 treatments. This system has four applicators, a water-cooling system, and a belt design for hands-free operation. Touch sensors are present to allow for confirmation of proper placement and skin contact. Like other programmes, it uses uniform energy delivery to maximise safety, comfort, and results. A 2021 study of 29 patients showed an average fat reduction of 4.92% (p<0.001) and 8.6% (p<0.0001) at 6 and 12 weeks, respectively, with a 72% patient satisfaction rate38. There was less discomfort with this device (2.6/10), potentially due to increased cooling and changes in energy distribution as compared to other devices. Preliminary results from an ongoing study with the new Venus Bliss Max show a 90% improvement based on Global Aesthetic Improvement Scale (GAIS) assessment. Since these results are 1 month post-treatment and maximal results are seen after 3 months, these are expected to improve.

The most commonly reported AE with laser lipolysis was transient tenderness23,30. There were no serious or unexpected AEs in the mentioned studies. Self-limited nodules were seen rarely38. The homogenous energy distribution reduces the risk of burns/blisters and ‘shark bite’ demarcations, as seen with cryolipolysis. There have been no reports of abnormalities with serum lipid or liver chemistries.


Long used for other pathologies, such as kidney stones or fibroids, ultrasound began being studied for fat reduction purposes in pigs in 201139. Since then, the technology has grown in popularity; a total of 134,506 ultrasound procedures were performed in 20193. Ultrasound devices can be categorised as either low-frequency or high-frequency.

Low-frequency ultrasound devices apply non-thermal, pulsed ultrasound waves that induce cavitations with minimal elevation temperature in the treated tissue. The mechanical disruption selectively destroys fat cell membranes, resulting in fat cell death and subsequent removal by the body’s natural mechanisms31. The surrounding tissue, blood vessels, and nerves are unharmed. 

High-frequency ultrasound devices cause direct heating by precisely focusing ultrasound energy at a controlled depth to induce vibrations of adipose tissue molecules. This generates heat, raising the temperature of subcutaneous tissue higher than lasers, ranging from 56°C to as high as 70°C. The high heat induces coagulative necrosis of fat cells while sparing nearby nerves and vessels. Ultrasound energy also stimulates collagen remodelling and has thus been used to tighten skin as well30. However, the higher temperature also has the potential for nonselective cell necrosis, and the procedure can require analgesia, as opposed to other modalities. 

UltraShape® (Syneron Candela, Wayland, MA) and LipoSonix® (Solta Medical, Bothell, Washington) are the only low- and high-frequency ultrasound devices, respectively, that have been FDA-approved for lipolysis. Significant changes in abdominal circumference, ranging from -2.1cm to -4.7cm, have been reported in multiple studies involving hundreds of patients with both devices2,40-46. For example, Jewell et al. performed a randomised sham-controlled study with Liposonix in 180 patients demonstrating an average waist circumference reduction of 2.10 cm (P=0.04) and 2.52 cm (P=0.002) at 47-J/cm2 and 59-J/cm2 energy levels, respectively, and a 75.5% (P<0.001) improvement on the GAIS40. Ultrasound devices do, however, show lower satisfaction rates when compared to other lipolysis devices, ranging from 47.5–85%2

Several studies combine ultrasound with other technologies, such as RF22,47. As discussed previously, the new Accent Prime platform combines both ultrasound and RF technologies to provide fat reduction, body contouring, and skin tightening. This system utilises ‘hot’ compression ultrasound waves and ‘cold’ shear ultrasound waves, which propagate waves at a perpendicular angle to target fat cells and protect the rest of the skin. The results have shown higher differences than HIFU studies alone, but head-to-head studies are needed for definitive conclusions.

Ultrasound devices are well-tolerated with little pain, though high-frequency devices may cause more discomfort during treatment due to the high temperature48. As with other modalities, the procedure is safe with minimal to no serious AEs. Common AEs include transient erythema, pain, and bruising. Long-term follow-up safety data revealed no dimpling, indurations, burns, or scars. Like other devices, no changes in serum lipid, markers of inflammation, or liver function studies have been reported2,30.


Non-invasive, energy-based fat reduction procedures have become increasingly popular and more widely available as compelling alternatives to surgical approaches. Ample data exists to support the capability of these devices to induce a clinically significant reduction of stubborn areas of fat that may be otherwise resistant to diet and exercise. Multiple devices have demonstrated consistent fat reduction in various areas of the body and in patients of all skin types, races, ages, and sexes. Furthermore, the data supports the long-term durability of results spanning years. 

The technologies currently in use have proven to be extremely safe with a limited side effect profile and are well-tolerated by most patients. Recent innovative product developments in software and hardware have reduced AEs and optimised patient comfort as well. Serious AEs are rare, isolated events, and seem to be reduced further by newer models.

Patient satisfaction constitutes a key metric in evaluating device efficacy. Indeed, numerous investigations and multifaceted assessments have revealed high levels of satisfaction with this technology. Even so, it remains important for providers to select patients appropriate for the procedure and to set realistic expectations prior to the initiation of therapy. Suitable candidates for non-invasive fat reduction include non-obese patients with localised, discrete collections of fat. Using the data, providers can estimate a modest amount of fat removable with a single session, keeping in mind that multiple sessions may be needed. Furthermore, it should be emphasised to patients that fat reduction is gradual and takes place over weeks to months post-treatment.

The four different modalities discussed differ by mechanism and have varying side effect profiles but have all been proven to be effective options for non-invasive lipolysis. Eventually, it may be unnecessary to choose between modalities, since many advanced systems are equipped with multiple technologies that can provide combination treatments to deliver even more individualised treatment regimens. Already, newer multifunctional designs can tighten and smooth skin, improve cellulite, and tone muscle in addition to removing fat.         

Despite the breadth of supporting evidence, further research is needed. At the time of this review, there remains a shortage of large randomised clinical trials, which can provide more reliable results with a higher statistical power. Furthermore, there is considerable heterogeneity among existing studies, making it difficult to conduct meta-analyses and strengthen conclusions. Uniform experimental parameters with standardisations in treatment protocol, follow-up time, and outcome measurements may enhance findings. The specifics of protocols, such as post-treatment massage and the optimal number of treatments remain unknown and could be further investigated. In addition, newer systems and applicators should be analysed to validate improvements in efficacy and patient comfort. Head-to-head studies directly comparing various existing technologies, as well as combination studies, will assist in determining optimal technology for specific patients and potential synergistic effects. Overall, larger-scale, more longitudinal studies will aid with confirmation of the durability of fat reduction and the discovery of any long-term sequelae. 


The current evidence confirms both the safety and efficacy of existing non-invasive fat reduction technologies. Cryolipolysis, RF, laser, and ultrasound have proven to be fantastic alternatives to traditional surgical methods for measurable and reproducible fat reduction. Growing demand is driving ongoing advancements in the field, including more effective, comfortable, and individualised treatments. Although multiple studies have corroborated the efficacy of these therapies, there remains a need for more randomised controlled trials with larger sample sizes and standardised treatment protocols to further validate these results and optimise patient outcomes.

Declaration of interest Dr. Michael Gold is a consultant and performs clinical research for the following: Allergan Aesthetics, an AbbVie Company, Cutera, Venus Concepts, Cynosure, Alma Lasers


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