Peptide Weight-Loss Shots and Knee Arthritis: What the New Retatrutide Study Means for Your Joints

If you have knee arthritis and you've thought about a weight-loss shot, a big new study is worth knowing about. This fall, the New England Journal of Medicine published TRIUMPH-1, a large trial of an experimental weekly shot called retatrutide.¹ Among the people in the study who had knee arthritis, those who took the drug lost a lot of weight and had less knee pain than those who got a placebo (a shot with no medicine in it).

That's encouraging news. It also raises fair questions. Does losing weight fix arthritis? Is the drug safe? Can you get it now? And what if your knee still hurts after the weight comes off? As an orthopedic surgeon who treats knee arthritis without surgery, here's my take.

One note before we start: Texas Orthobiologics does not prescribe weight-loss medicines. This article is here to help you understand the research and talk it over with your own doctor.

What Is Retatrutide?

You've probably heard of semaglutide (Wegovy and Ozempic) and tirzepatide (Zepbound and Mounjaro). These weekly shots copy natural gut hormones that help control hunger and blood sugar. Semaglutide works on one of these hormone signals, called GLP-1. Tirzepatide works on two. Retatrutide, made by Eli Lilly, works on three: GLP-1, GIP and glucagon.¹ That's why you may see it called a "triple agonist." Like semaglutide and tirzepatide, retatrutide is a peptide, a short chain of amino acids, which is why these medicines are often called peptide weight-loss shots.

Retatrutide is still experimental. It is not approved by the U.S. Food and Drug Administration (FDA). Lilly has said it plans to apply for FDA approval in early 2027.²

What the TRIUMPH-1 Study Found

• Who was in it: 2,339 adults with obesity who did not have diabetes. They got a weekly shot of retatrutide (4, 9 or 12 mg) or a placebo for 80 weeks, about a year and a half.¹ Everyone, including the placebo group, also got advice on healthy eating and physical activity.³
• Weight loss: On average, people lost 17.6%, 23.7% and 25.0% of their body weight on the three doses, compared with 3.9% on placebo.¹ For a 250-pound person, 25% is about 62 pounds.
• Knee pain: 574 people in the study had knee arthritis. On a 10-point knee pain scale, pain dropped by about 3.5 points on the two higher doses, compared with 1.9 points on placebo.¹ In other words, the drug added about 1.6 to 1.8 points of pain relief on top of what the placebo group got.
• Side effects: The most common side effects were stomach and gut problems.¹

A second study, TRIUMPH-4, looked only at people with obesity and knee arthritis. In early results Lilly released in December 2025, 445 people took retatrutide (9 or 12 mg) or a placebo for 68 weeks. Average weight loss was as high as 28.7%, and knee pain scores fell more than with placebo.⁴ As of this writing, the full TRIUMPH-4 results have not been published in a medical journal, so we'll wait for the complete details.

Why Weight Matters So Much for Your Knees

These results fit with what we've known for years. Your knees carry your body weight with every step. In one study of older adults with knee arthritis, each pound lost meant about 4 pounds less force on the knee with each step.⁵ Over thousands of steps a day, that adds up.

Weight loss without drugs helps too. In the IDEA trial, people with knee arthritis who lost about 11% of their body weight through diet plus exercise had less knee pain and better function than people who only dieted or only exercised.⁶ And in 2024, a study of semaglutide in people with obesity and knee arthritis also found less knee pain than with placebo.⁷

What This Study Doesn't Tell Us

• It's about pain, not new cartilage: The knee results reported so far are about pain and how well people could move. They don't show that the drug rebuilds worn cartilage or reverses arthritis.
• The placebo group improved too: People on placebo lost about 4% of their weight, and their knee pain fell by 1.9 points.¹ Healthy eating, activity and a little weight loss matter, with or without a drug.
• Not everyone can stay on it: In TRIUMPH-4's early results, 12% to 18% of people on retatrutide stopped because of side effects, compared with 4% on placebo. About 9% to 21% had dysesthesia, an unusual skin feeling such as tingling or sensitivity. Lilly said most of these cases were mild.⁴
• Muscle can go with the fat: When people lose a lot of weight on these drugs, part of what they lose is lean mass, which includes muscle. Studies differ widely on how much.⁸ Your leg muscles help support your knees, so strength training matters while you lose weight.
• You can't safely get it yet: Outside of clinical trials, retatrutide isn't available as an approved prescription. The FDA says retatrutide can't be used in compounding under federal law. It has also warned companies that sold retatrutide online labeled "for research purposes" or "not for human consumption," and it urges people not to buy these products because their quality is unknown and they may be harmful.⁹

What If Your Knee Still Hurts After the Weight Comes Off?

Losing weight can take a lot of stress off your knees. But weight is only one part of arthritis. Worn cartilage, a torn meniscus, inflammation inside the joint and weak muscles can keep a knee hurting even at a healthier weight. That's where we come in.

At Texas Orthobiologics, we treat knee arthritis without surgery and without steroids, using treatments made from your own body:

• PRP (platelet-rich plasma): We draw your blood and spin it to concentrate the platelets, which carry growth factors and other signaling proteins that help direct healing.
• BMAC (stem cells) (bone marrow aspirate concentrate): We take a small amount of bone marrow, usually from the back of the hip bone, and concentrate it.

PRP is one of the most studied orthobiologic treatments for knee arthritis. A 2025 review of 18 randomized trials with 1,995 patients found that PRP improved pain and function more than placebo injections, and that PRP with higher platelet counts gave better pain relief than PRP with lower counts.¹⁰ That's one reason we measure the platelet dose in every PRP treatment we give. Research on BMAC (stem cells) for the knee is at an earlier stage, and more high-quality trials are needed.

Weight loss and orthobiologics don't compete with each other. One lightens the load on your knee. The other is aimed at the joint itself. If you're losing weight with your doctor's help, let us know about every medicine you take, including weight-loss shots, so we can plan your care.

How We Treat Knee Arthritis

1. A clear diagnosis first. We examine your knee, review your imaging and find out what is causing your pain.
2. Your own cells, prepared in the office. Depending on your knee, we use PRP or BMAC (stem cells), prepared during your visit.
3. Precise placement with image guidance. We use image guidance to place the treatment where it's needed.
4. Home the same day. PRP and BMAC (stem cells) visits each take about an hour in our Dallas office. You go home with clear instructions for the weeks ahead.

Because PRP and BMAC (stem cells) come from your own body, the risk of an allergic reaction to the treatment itself is very low. Like any injection, they still carry some risk, such as soreness, bruising and, rarely, infection. We'll go over these with you before you decide.

Orthobiologics are not a quick fix. Your body's response builds over weeks, not days.

Who's Treating Your Knee

I'm an orthopedic surgeon, board-certified by the American Board of Orthopaedic Surgery. I serve as Chairman of the Biologic Association for 2026 to 2027, I'm a two-term past President of the Interventional Orthobiologics Foundation (IOF), and I'm the Founding Editor of the Biologic Orthopedics Journal. Since 2008, I've directed the Las Vegas Regenerative Medicine and MSK Ultrasound Course, which has trained more than 2,500 clinicians. As a surgeon, I can walk you through every option, including surgery, before you decide.

Hear It From Our Patients, for Free

More than 100 of our patients have shared their stories on video. You can watch them anytime on our YouTube patient testimonial library, free.

These videos share individual patient experiences. The people in them are patients, not medical professionals, and were not paid or given discounts or free care for their stories. Every patient is different, and results vary.

When to See a Doctor Right Away

See a doctor right away if your knee suddenly becomes hot, red and swollen, especially with a fever, or if you can't put weight on it after an injury.

Explore Your Options

Whether or not you're on a weight-loss plan, if knee arthritis is slowing you down, come talk with us. We'll find out what's causing your pain, explain your options and your investment, and help you decide what's right for you, with no pressure.

Texas Orthobiologics is at 3310 Live Oak, Suite 202, in Dallas. Call (877) 777-8883 or request a visit online.

Areas We Serve

Our office is in Dallas, and patients come to us from across North Texas, including:

• Dallas and nearby: Highland Park & University Park, Irving, Richardson, Garland, Carrollton and Coppell
• Collin County: Plano, Frisco, McKinney, Allen and Prosper
• Northwest and Tarrant County: Grapevine, Southlake, Colleyville, Keller, Flower Mound and Fort Worth

Disclaimer: This article is for educational purposes only and is not medical advice. Texas Orthobiologics does not prescribe weight-loss medicines. Retatrutide is an investigational drug and is not FDA-approved. PRP and BMAC (stem cells) are not FDA-approved treatments for knee arthritis. Individual results vary. Please talk with a qualified physician about your specific condition and before starting or stopping any medicine.

References

1. Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity. N Engl J Med. 2026;395(18):1781-1793. doi:10.1056/NEJMoa2604169. Abstract
2. Jensen K. Lilly, with new data, to seek FDA approval of obesity drug retatrutide. BioPharma Dive. Published July 23, 2026. Accessed November 9, 2026. https://biopharmadive.com/news/lilly-retatrutide-fda-application-obesity-drug-results/825987/
3. Giblin K, Kaplan LM, Somers VK, et al. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: rationale and design of the TRIUMPH registrational clinical trials. Diabetes Obes Metab. 2026;28(1):83-93. doi:10.1111/dom.70209. Abstract | Free full text
4. Eli Lilly and Company. Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial. Press release. December 11, 2025. Accessed November 9, 2026. https://lilly.gcs-web.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average
5. Messier SP, Gutekunst DJ, Davis C, DeVita P. Weight loss reduces knee-joint loads in overweight and obese older adults with knee osteoarthritis. Arthritis Rheum. 2005;52(7):2026-2032. doi:10.1002/art.21139. Abstract
6. Messier SP, Mihalko SL, Legault C, et al. Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial. JAMA. 2013;310(12):1263-1273. doi:10.1001/jama.2013.277669. Abstract | Free full text
7. Bliddal H, Bays H, Czernichow S, et al. Once-weekly semaglutide in persons with obesity and knee osteoarthritis. N Engl J Med. 2024;391(17):1573-1583. doi:10.1056/NEJMoa2403664. Abstract
8. Neeland IJ, Linge J, Birkenfeld AL. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes Obes Metab. 2024;26(suppl 4):16-27. doi:10.1111/dom.15728. Abstract
9. US Food and Drug Administration. FDA's concerns with unapproved GLP-1 drugs used for weight loss. Updated October 1, 2026. Accessed November 9, 2026. https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss
10. Bensa A, Previtali D, Sangiorgio A, Boffa A, Salerno M, Filardo G. PRP injections for the treatment of knee osteoarthritis: the improvement is clinically significant and influenced by platelet concentration: a meta-analysis of randomized controlled trials. Am J Sports Med. 2025;53(3):745-754. doi:10.1177/03635465241246524. Abstract | Free full text