Retatrutide eases knee osteoarthritis pain and lowers weight in adults with obesity

Key takeaways:

• Retatrutide lowered knee osteoarthritis pain significantly more than placebo after 80 weeks.
• Patients receiving the highest dose lost an average of 25% of body weight.

In adults with obesity but without diabetes, retatrutide was linked with meaningful reductions in both knee osteoarthritis pain and body weight, according to results published in The New England Journal of Medicine.

“Retatrutide is a triple-receptor agonist targeting the G-protein-coupled receptors for glucose dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon,” Ania M. Jastreboff, MD, PhD, of the Yale University School of Medicine, and colleagues wrote. “In a phase 2 trial involving participants with obesity, once-weekly subcutaneous retatrutide (at a dose of 12 mg) resulted in a mean weight reduction of 24.2% at 48 weeks and improved multiple cardiometabolic measures, including waist circumference, systolic and diastolic blood pressure, glycated hemoglobin, and lipid levels. In a substudy, the same regimen of retatrutide resulted in a significant reduction in liver fat.”

To further evaluate retatrutide (Eli Lilly & Co.) for safety and efficacy, Jastreboff and colleagues carried out the phase 3 TRIUMPH-1 trial, a randomized, double-blind, placebo-controlled study that enrolled 2,339 adults with obesity and without diabetes. The trial was conducted at 121 sites in 11 countries.

Participants were assigned to receive weekly subcutaneous injections of 4 mg retatrutide (n = 584), 9 mg retatrutide (n = 584), 12 mg retatrutide (n = 584) or placebo (n = 587) for 80 weeks. The researchers also included a subgroup of 574 patients with moderate to severe knee osteoarthritis and 243 patients with obstructive sleep apnea. Main outcomes included percent change in body weight, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores and apnea-hypopnea index.

After 80 weeks, mean body weight fell by 17.6%, 23.7%, 25% and 3.9% in the 4 mg, 9 mg, 12 mg and placebo groups, respectively, the investigators reported. Mean WOMAC scores declined by 3.2 points, 3.5 points, 3.6 points and 1.9 points in those same groups.

Retatrutide also significantly reduced apnea-hypopnea events in patients with obstructive sleep apnea and improved cardiometabolic markers, including systolic blood pressure, triglycerides and high-sensitivity C-reactive protein. Treatment discontinuation rates were 4.1%, 6.5%, 11.1% and 4.6% in the 4 mg, 9 mg, 12 mg and placebo groups, respectively. The most common treatment-related adverse events were nausea, diarrhea and constipation.

“In this trial, retatrutide resulted in a reduction in pain of up to 61.6%,” Jastreboff and colleagues wrote.

“Participant-reported outcomes supported improvements in quality of life, including physical function and psychosocial domains,” they added.

Sources/Disclosures

Source:

Disclosures: Jastreboff reports receiving research support from Amgen, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Rhythm Pharmaceuticals; and consulting for Amgen, AstraZeneca, Biohaven Pharmaceuticals, Boehringer Ingelheim, Eli Lilly, i2o Therapeutics, Intellihealth, Kailera, Metsera, Novo Nordisk, Pfizer, Regeneron, Rhythm Pharmaceuticals, Roche/Genentech, Scholar Rock, Structure Therapeutics, Terns Pharmaceuticals, Viking, Wave, Weight Watchers and Zealand Pharma. Please see the study for all other authors’ relevant financial disclosures.

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