What’s New in Weight Loss Medications and The Resulting Loose Skin
New data has just been released on the next generation of weight management and metabolic optimization peptides. This is generating weight loss numbers that were unheard of 5 years ago. In a new clinical study published in the New England Journal of Medicine, Cagrilintide was coadministered with Semaglutide in adults with obesity.
Groundbreaking Study on Cagrilintide and Semaglutide Combination
This study was a 68-week multicenter study enrolling adults without diabetes for weight loss. These patients had a body mass index of 30 or greater. The body mass index (BMI) is calculated by the weight in kilograms divided by the square of the height in meters. A total of 3417 participants with 2108 assigned to receive the combination of both semaglutide at 2.4 mg and cagrilintide at 2.4 mg, or semaglutide alone or cagrilintide alone. Although all participants using the combination or either drug alone had weight loss, the combination achieved superior results up to 30% loss of body weight. Side effects with the combination was 79.6% with the combination and 39.9% in the placebo group. These were mild and transient including nausea, vomiting, diarrhea and constipation.
How Cagrilintide Works to Enhance Satiety and Weight Loss
Cargrilintide is a long-acting amylin analogue, a synthetic cousin of the hormone amylin which is naturally secreted along with insulin from the pancreas. Amylin works in blood sugar regulation and satiety. It signals through the brain to “stop eating” and aids in blood sugar regulation.
Weight Loss Outcomes Compared: CagriSema vs Semaglutide Alone
In the study above, when semaglutide was paired with cargrilintide, all participants lost an average of 20.4% of their total body weight over the 68-week period of the study. Semaglutide alone produced a 15% reduction and cagrilintide alone reduced weight by 11-12%. This is a significant reduction when combined and the researchers theorized that each works at the receptor level.
Mechanisms of Action: GLP-1 and Amylin Pathways
GLP-1 agonists increase insulin secretion and suppress glucagon. They also slow gastric emptying making the patient feel full for a longer period after eating. Cagrilintide acts on the amylin pathway, delivering satiety signals directly to the brain. It also retards gastric emptying rates. The side effects are similar to the GLP-1 medications, but it has been reported that cagrilintide can cause an emotional flat affect. The dosage is .25mg 2-3 times a week with the GLP-1 and titrate up.
Retatrutide and Future Triple Agonist Therapies
When added to Retatrutide, the triple agonist, this combination should reduce weight by 30-40%. This combination is currently under investigation. Initially, the Glucagon like peptide -1 (GLP-1) was introduced then the Dependent Insulinotropic Polypeptide Dual Agonist (GIP) and finally the triple action of Retatrutide which adds the glucagon receptor agonists.
Study
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity
Published June 22, 2025, DOI:10.1056/NEjMoa2502081 PMID 40544433
Background: Semaglutide at a dose of 2.4mg has established weight loss and cardiovascular benefits and Cagrilintide at a dose of 2.4 mg has shown promising results in early phase trials, the efficacy of the combination known as CagriSema on weight loss in persons with either overweight or obesity is unknown.
Conclusion: cagrilintide-semaglutide provided significant and clinically relevant body weight reductions in adults.
Study
Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes
N Engl J Med 2025 Jun 22 PMID 40544432
Background: Cagrilintide and Semaglutide have been each shown to induce weight loss as monotherapies. Data are needed on the coadministration of cagrilintide and semaglutide for weight management in adults with type 2 diabetes.
Conclusions: Once weekly cagrilintide semaglutide resulted in a significantly lower body weight in adults with type 2 diabetes and obesity.
The Impact of Weight Loss on Muscle Mass and Skin Laxity
The amount of weight loss that can be provided by this combination of peptides is beyond significant. Ultimately, there will be a huge reduction in diabetes, cardiovascular disease, hypertension, strokes and other major diseases. However, there will be other consequences to this amount of weight reduction. With weight reduction, many patients lose an appreciable amount of muscle mass unless weight training is part of the overall protocol. Large weight reduction, with loss of muscle equates into loose skin, obvious stretch marks, creepy skin, and visible cellulite. Jelly Roll, the country rocker, recently formally announced his major weight loss and plans for needed plastic surgery to remove loose skin. With millions of Americans on GLP-1 meds and losing weight, not every patient can afford to obtain plastic surgery.
What Are the Alternative Options for Loose Skin, Fat Pockets and Striae?
Platelet Rich Plasma
Platelet Rich Plasma is an autologous blood concentrate that is rich in cytokines, growth factors and bioactive proteins. PRP has been used in all fields of medicine and is well established for its regenerative capabilities. In striae distensae, which are dermal scars associated with atrophy of the epidermis, PRP is extremely effective. Biopsies taken after the use of PRP on stretch marks show collagen and elastin fibers were increased.
Study
Platelet Rich Plasma Versus Tretinoin in Treatment of Striae Distensae: A Comparative Study
Dermatol Surg 2018 May;44(5):697-704 PMID 29701622
Objective: To evaluate the effect and safety of intralesional injection of platelet rich plasma versus topical tretinoin in the treatment of SD.
Conclusion: PRP injection and topical tretinoin are safe for the treatment of SD, but PRP is more effective, and it gives better therapeutic response than tretinoin.
PhysioPRO Shockwave Therapy System
Extracorporeal shockwave therapy (ESWT) is a noninvasive treatment option for improving skin laxity and body contouring. It utilizes acoustic waves to stimulate collagen production and enhance skin elasticity. When employed in a targeted area, high energy waves promote blood circulation and cellular repair. The collagen and increased vascularity can tighten skin over time. ESWT is effective for sagging skin in areas such as the abdomen, thighs and triceps. It can also assist in reducing the appearance of cellulite. Results vary by the individual and take several weeks to become noticeable as collagen builds. Multiple treatments are needed often spaced weeks apart and side effects to the therapy with the shockwave are minimal.
Study
Cellulite and Focused Extracorporeal Shockwave Therapy for Non-invasive Body Contouring: A Random Trial
Dermatol Ther 2013 Dec 3;(2):143-155 PMID 24297647
Conclusion: ESWT and gluteal strength training improved cellulite and contoured the buttock area by 24% over control groups.
Radiofrequency
Radiofrequency skin tightening is another nonsurgical treatment to treat sagging skin. Radio frequency devices use safe levels of low frequency electromagnetic waves to generate heat. The heat penetrates deep into the layers of the skin. There, it stimulates new skin regeneration by stimulating the production of collagen and elastin. Collagen and elastin provide the skin cells with more strength and flexibility. This process results in the skin regaining its prior shape and feel. Radiofrequency improves the skin tone, texture and firmness and reduces the skin’s wrinkles, fine lines and sagginess. RF is utilized in body contouring especially in the face, neck, arms and hands.
Study
Noninvasive Radio Frequency for Skin Tightening and Body Contouring
Cutan Med Surg 2013 Mar;32(1):9-17 PMID 24049924
RF thermal stimulation is believed to result in a microinflammatory process that promotes new collagen. By manipulating skin cooling, RF can be used for heating and reduction of fat. Currently, the most common use of RF based devices are to noninvasively manage and treat skin tightening of lax skin (including sagging jowls, abdomen, thighs and arms) as well as wrinkle reduction, cellulite improvement and body contouring.
Low Level Laser Therapy
The use of low-level laser therapy (LLLT) is called photobiomodulation. Photobiomodulation therapy is defined as a form of light therapy that utilizes nonionizing light sources in the visible (400-700) electromagnetic spectrum. Gaining popularity in clinical practice for body contouring, the treatment protocols vary depending on the adipose makeup of the patient.
Study
Photobiomodulation Therapy for Improvement of Body Contour: A Retrospective Study on Middle Eastern Participants
Iran J Public Health 2024 Aug;53(8):1858-1863 PMID 39415875
Background: The rising demand for body contouring and concerns about side effects of invasive surgical procedures have led to advances in providing new noninvasive alternative methods for weight reduction. The current retrospective study investigated the safety and efficacy of photobiomodulation technology in reducing local obesity in Middle Eastern participants.
Conclusion: This study demonstrated the effectiveness and safety of photobiomodulation in reduction of circumferential size in abdomen, buttock, thigh and arm areas in Middle Eastern participants with high patient satisfaction an acceptable safety profile.
Juventix Regenerative Solutions for Post-Weight Loss Skin Tightening
These are a few of the options available for the treatment of loose skin and pockets of fat deposits that occur after a significant weight reduction. Surgery is not the only option. Juventix Regenerative Medical is an industry leader in the regenerative medical field. Our Platelet Rich Plasma Kits are FDA cleared and designed for safety, sterility and effectiveness and are currently being utilized by regenerative professionals around the world. However, Juventix Regenerative Medical has so much more to offer. In the treatment of body contouring, the PhysioPRO is a clinical grade extracorporeal shockwave device that induces intracellular and extracellular reactions to regenerate and tighten tissues.
Juventix Regenerative Medical offers the Apollo Duet. This device incorporates three aesthetic applications, electroporation and ionophoresis to penetrate the skin without the use of a needle and achieve penetration of serums into the deeper layers of the skin. The second modality is 4th generation radio frequency to stimulate collagen and elastin production to tighten loose skin areas.
Juventix Regenerative Medical also offers the Gemstone Laser. This device generates 532 wavelength light to stimulate cellular lipolysis. This removes stubborn fat deposits by working at the cellular level to open the fat cells and their contents are dissipated naturally by the body. This results in body tightening and sculpting. All without needles or pain. Improvements can be visualized in as little as two treatments.
Dramatic weight loss is now commonplace and so is loose, lax skin with pockets of fat.
Juventix Regenerative Medical has the solutions.
RESTORE, REVIVE, REGENERATE – JUVENTIX REGENERATIVE MEDICAL
Regenerative Regards,
Dr. Robert McGrath
