TL;DR
Get workout gear delivered free with Prime
- Fast, free delivery on millions of items
- Prime Video, Amazon Music and more included
- Member-only deals all year
In the TRIUMPH-4 trial, people with obesity and knee osteoarthritis who received weekly retatrutide reported larger reductions in pain and disability than those given placebo after 68 weeks. They also lost substantial weight, while withdrawals due to adverse events were more frequent; the drug remains investigational, and its effects on joint disease itself are not established.
Retatrutide reduced knee osteoarthritis pain and disability more than placebo over 68 weeks in a trial of 445 people with obesity and knee OA, researchers reported at the American College of Rheumatology annual meeting. Participants receiving the investigational weekly injection also lost substantial weight, but adverse-event withdrawals were higher than in the placebo group, and the results do not establish that the drug changes or repairs the joint disease.
In TRIUMPH-4, participants were assigned to weekly injections of placebo or retatrutide at 9 mg or 12 mg. The trial included people with a body-mass index above 27 and knee osteoarthritis. At week 68, average WOMAC pain scores had fallen by 4.48 points with 9 mg and 4.41 points with 12 mg, compared with a 2.43-point fall with placebo. WOMAC is a standardized measure of osteoarthritis pain and function; higher scores indicate worse symptoms.
Function scores also improved more in the retatrutide groups: by 4.14 points with 9 mg and 4.20 points with 12 mg, compared with 2.06 points with placebo. About 70% of participants in each retatrutide group had a 70% reduction in pain scores, versus 26% of those given placebo, according to the report. The placebo group also received individualized dietary counseling and encouragement to exercise at least 150 minutes a week, which may help explain its improvement.
Weight loss was another primary outcome. The report said participants receiving retatrutide lost more than one-quarter of their body weight by week 68, with losses continuing during the trial. Some participants stopped treatment because they considered their weight loss excessive. Retatrutide acts on receptors for GLP-1, GIP and glucagon. The study findings and a report on the related TRIUMPH-1 trial were published simultaneously in the New England Journal of Medicine.
Pain Relief Alongside Major Weight Loss
Knee osteoarthritis can limit walking and everyday activities, while obesity can add mechanical load to the knee. The reported reductions in pain and disability suggest that a medication producing substantial weight loss may also help symptoms for some people with obesity and knee OA. That is relevant to patients seeking options beyond pain management and exercise, particularly because the trial included many participants with substantial joint damage: 63% had Kellgren-Lawrence grade 3 OA, according to presenting investigator Thomas Conaghan.
The results do not show that retatrutide is a treatment for all osteoarthritis or that it prevents further joint damage. Researchers proposed that lower body weight could reduce stress on the knee and that changes in adipose tissue might affect inflammation, but the mechanism of pain improvement remains uncertain. The trial also recorded a meaningful difference in tolerability: 13% of the 9-mg group and 18% of the 12-mg group withdrew because of adverse events, versus 4% with placebo. About 10% in each active-treatment group had serious adverse events, compared with 2% in the placebo group.
Products Worth Considering
BowFlex Results Series SelectTech Adjustable Dumbbells, Pair
Bowflex SelectTech 840 Adjustable Kettlebell
Withings BPM Connect Blood Pressure Monitor with Wi-Fi and Bluetooth
As an affiliate, we earn on qualifying purchases.
How TRIUMPH-4 Tested Retatrutide
TRIUMPH-4 enrolled 445 participants from the United States, Canada, Mexico, Australia and Spain. Participants were allocated in roughly equal numbers to placebo, 9 mg of retatrutide or 12 mg, administered by weekly injection. Average baseline BMI was 40.4, and average body weight was 113 kilograms. About 63% of participants were women. All groups were asked to follow a structured lifestyle program, including dietary counseling and a physical-activity target.
Retatrutide is an investigational drug that targets three hormone receptors involved in metabolic regulation: GLP-1, GIP and glucagon. The report places TRIUMPH-4 alongside TRIUMPH-1 and other research into weight-loss medicines and osteoarthritis symptoms. New American College of Rheumatology guidance has also placed greater emphasis on weight loss in osteoarthritis management. Those developments provide context, but do not mean that retatrutide has been approved for OA or that findings in this selected group apply to people without obesity.
Joint Effects and Risks Need Study
The trial report does not establish whether retatrutide slows, reverses or otherwise modifies osteoarthritis in the joint. The researchers called for further studies of the mechanisms behind pain reduction and the drug’s potential as a disease-modifying therapy. It is also unclear whether similar benefits would occur in people with osteoarthritis who do not have obesity, or how the balance of benefit and risk would look with longer use.
Adverse events are a key part of interpreting the findings. Gastrointestinal problems were the most common, while withdrawals and serious adverse events were more frequent in the retatrutide groups than with placebo. The supplied report does not provide the full breakdown of all adverse-event types or their longer-term outcomes. Retatrutide is described as investigational; these results alone do not establish regulatory approval, routine availability or suitability for individual patients.
Further Trials Must Test Long-Term Effects
The next evidence needed includes longer follow-up on pain, physical function, weight change and adverse events, as well as research testing whether the treatment affects the underlying joint disease. Studies could also clarify whether benefits are driven mainly by reduced knee loading, changes in inflammation, or a combination of factors. Until those questions and the drug’s regulatory status are resolved, the TRIUMPH-4 findings are evidence of symptom and weight changes in a specific study population—not a basis for assuming retatrutide is an established osteoarthritis treatment.
Key Questions
What did the TRIUMPH-4 trial find?
Among participants with obesity and knee osteoarthritis, average pain and disability scores improved more over 68 weeks with weekly retatrutide than with placebo. The retatrutide groups also lost substantial weight.
How much did knee pain scores change?
On the WOMAC pain measure, scores fell by 4.48 points with 9 mg and 4.41 points with 12 mg of retatrutide, compared with a 2.43-point decrease with placebo.
Does retatrutide repair or slow osteoarthritis?
The reported trial results do not establish that. Researchers said further studies are needed to determine whether retatrutide changes the joint disease itself and to understand how it may reduce pain.
What safety concerns were reported?
Withdrawals because of adverse events occurred in 13% of the 9-mg group and 18% of the 12-mg group, compared with 4% with placebo. Serious adverse events were reported in about 10% of each retatrutide group and 2% of the placebo group; gastrointestinal events were the most common.
Is retatrutide an approved osteoarthritis treatment?
The source describes retatrutide as investigational. The TRIUMPH-4 results do not establish that it is approved or routinely available for osteoarthritis.
Source: medpagetoday.com
