Deoxycholic acid in the treatment of submental fat

What is deoxycholic acid?

Deoxycholic acid is a secondary bile acid produced by intestinal bacteria acting on primary bile acids secreted by the liver. Deoxycholic acid is also known as deoxycholate and cholanoic acid.

• Deoxycholic acid emulsifies fats to aid their intestinal absorption.
• When injected into subcutaneous fat, deoxycholic acid destroys adipocytes (fat cells). The inflammatory tissue reaction leads to a reduction in fat and minimal scarring.
• Deoxycholic acid is less destructive in skin and muscle tissue due to protein binding.
• Kybella^® (Allergan) is a proprietary formulation of purified synthetic deoxycholic acid initially developed by Kythera Biopharmaceuticals for therapeutic use. In some countries, including New Zealand, it is marketed as BELKYRA®.

What is deoxycholic acid used for?

Deoxycholic acid and its derivatives have been used:

• In the food industry as emulsifiers
• To prevent and dissolve gallstones
• Under investigation as a biological detergent
• In mesotherapy to produce lipolysis (eg, as non-surgical treatment of lipoma)
• Kybella has US Food and Drug Administration approval as an injectable drug to improve the appearance of moderate to severe convexity or fullness associated with submental fat.

What is submental fat?

Submental fat refers to the fat present in the submental region underneath the chin and at the front of the neck (preplatsymal fat). Submental fat accumulates with age, genetic predisposition and obesity. It is considered cosmetically undesirable and can lead to an adverse psychological impact.

Options to minimise submental fat include:

• Surgical rejuvenation (lower face and neck lift)
• Targeted liposuction
• Cryolipolysis
• Laser ablation
• Radiofrequency contouring
• Ultrasound lipolysis
• Submentoplasty
• Chin implants
• Deoxycholic acid injections.

Submental fat may be assessed objectively by clinicians via the use of the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS).

The patient’s subjective assessment of their submental fat may be measured via the use of the following methods:

• The Subject Self-Rating Scale (SSRS)
• The Patient-Reported Submental Fat Rating Scale (PR-SMFRS).  

Precautions prior to deoxycholic acid injections into submental fat

• Postpone treatment if there is an infection at the treatment site.
• Avoid topical or local anaesthesia if the patient is allergic to these.
• Ensure the swelling is due to fat (consider thyromegaly, cervical lymphadenopathy, submandibular ptosis, scarring, and excessive skin laxity).

A careful clinical evaluation to exclude other causes of submental convexity/fullness (eg, enlarged thyroid, cervical lymphadenopathy) is mandatory prior to treatment. Treatment with deoxycholic acid is contraindicated:

• If the patient is sensitive to any component of the treatment drug
• If excess skin (rather than fat) is the cause of an adverse profile
• During pregnancy or lactation (there is insufficient safety data)
• If there has been a prior surgical or aesthetic treatment of the submental region
• If the patient has a bleeding disorder or is on anticoagulants or antiplatelet agents
• If there is current, or a prior history of, dysphagia (difficulty swallowing).

How is deoxycholic acid administered?

Deoxycholic acid injections should be performed by a trained clinician with an understanding of submental anatomy. The target is the subcutaneous fat between the dermis and platysma (pre-platysmal fat) within the treatment area. Prior informed consent should be obtained from the patient.

The following steps are a general guide (for specific details and recommendations for use, consult the manufacturer’s product information). A topical anaesthetic, ice, or local anaesthetic may be used but is not often required.

• An ink ‘tattoo grid’ can be applied to the area to be treated to guide the delivery of injections; this is removed with an alcohol-soaked swab following treatment.
• Deoxycholic acid is injected subcutaneously as 0.2 mL doses, 1 cm apart, into the submental fat treatment area. The concentration used is 10 mg/mL (2 mg/cm²). A 30 gauge (or smaller) 0.5-inch long needle is used.
• Up to 50 individual injections may be injected per treatment session, equivalent to a maximum of 10 mL of deoxycholic acid.
• Post-treatment bruising and pain may be alleviated by compression dressings, cold packs and oral analgesia.
• Treatment may be repeated at 4–8-week intervals. Most patients receive 2–4 treatments and up to six treatments may be administered.

What are the benefits of deoxycholic acid?

Five large clinical trials have demonstrated the efficacy of deoxycholic acid in the reduction of submental fat as measured by validated scales and objective measurements. Patients reported improved psychological parameters and feelings. Adverse effects were mild and temporary.

In a randomised trial that included 390 patients, 12 weeks after four treatments with deoxycholic acid, 65–70% of patients treated with deoxycholic acid were satisfied with the appearance of their face and chin compared with 30% who had received injections of inert saline (placebo).

What are the disadvantages, side effects and risks of deoxycholic acid injections?

Deoxycholic acid injections into the submental fat are generally well tolerated and side effects are usually transient. However, in clinical trials, more patients treated with deoxycholic acid 1 mg/cm² and 2 mg/cm² discontinued treatment because of adverse events (5.8% and 11.5%, respectively) compared with placebo (0.9%).

Side effects of the procedure are common and include:

• Pain at the injection site  
• Bruising
• Numbness and tenderness
• Temporary redness and swelling
• Induration at the site of injection
• Depressions at the site of injection
• Dysphagia
• Nerve injury causing temporary numbness
• Skin ulceration (rare), due to too superficial injection into the dermis
• Temporary or persistent beard hair loss has been reported.

Submental fat may re-accumulate following the procedure.

The safe and effective use of deoxycholic acid outside the submental fat region has not been established and is not recommended.