Pharma Friday – May 22, 2026

An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *

Lilly’s Retatrutide Delivered Powerful Weight Loss in Pivotal Phase 3 Obesity Trial

On May 21, Eli Lilly and Company, the maker of Zepbound (tirzepatide) and Foundayo (orforglipron), announced positive topline results from TRIUMPH-1, a Phase 3 clinical trial evaluating the efficacy and safety of retatrutide, an investigational, first-in-class GIP, GLP-1, and glucagon triple hormone receptor agonist, in adults with obesity or overweight and at least one weight-related comorbidity and without diabetes. At 80 weeks, all doses of retatrutide (4 mg, 9 mg, and 12 mg) met the primary and key secondary endpoints for obesity, delivering clinically meaningful weight loss.

“Obesity is a chronic disease, and people living with obesity deserve treatment options that match the complex biology of their neurometabolic disease,” said Ania Jastreboff, MD, PhD, professor of medicine and pediatrics (endocrinology) at the Yale School of Medicine, director of the Yale Obesity Research Center (Y-Weight), and lead investigator. “It was impressive to see that every dose of retatrutide resulted in clinically meaningful weight reduction for nearly all participants, and people with severe obesity on the highest dose lost on average 30% of their body weight over two years. Importantly, treatment with retatrutide not only resulted in robust weight reduction, but also in clear improvements in assessed cardiometabolic health measures. For patients I see in clinic, retatrutide may potentially be a highly impactful future tool to treat their obesity and transform their health trajectory.”

For the primary endpoint, participants taking retatrutide 9 mg and 12 mg lost an average of 64.4 lbs (25.9%) and 70.3 lbs (28.3%), respectively. Those taking the 4 mg dose of retatrutide, with just a single dose escalation step, lost an average of 47.2 lbs (19.0%). Notably, 65.3% of participants taking retatrutide 12 mg achieved a BMI <30, falling under the threshold for obesity at 80 weeks, including 37.5% of those who started with class 3 obesity (BMI ≥40).¹ In a pre-specified blinded extension for those with a BMI ≥35, participants who continued on retatrutide 12 mg to 104 weeks lost an average of 85.0 lbs (30.3%).² Additionally, retatrutide showed significant improvements from baseline across certain cardiovascular risk factors, including waist circumference, non-HDL cholesterol, triglycerides, systolic blood pressure and high-sensitivity C-reactive protein (hsCRP).

“TRIUMPH-1 highlights the importance of options and the potential for retatrutide to help people across various stages of their obesity journey,” said Kenneth Custer, PhD, executive vice president and president, Lilly Cardiometabolic Health. “From the 4 mg dose, reaching nearly 20% weight loss with one escalation step, to the 12 mg dose that delivered a level of weight loss long associated with bariatric surgery, retatrutide offers the potential for a patient-centric approach to obesity.⁴ Together with Zepbound and Foundayo, retatrutide could build on Lilly’s commitment to match treatments to the needs and preferences of patients.”

For the treatment-regimen estimand, each dose level of retatrutide led to improvements across the primary and key secondary endpoints, as well as the pre-specified extension, including:⁵

• Percent change in body weight at 80 weeks: -17.6% (-19.8 kg; -43.7 lbs; 4 mg); -23.7% (-26.7 kg; -58.9 lbs; 9 mg); -25.0% (-28.2 kg; -62.1 lbs; 12 mg) and -3.9% (-4.4 kg; -9.7 lbs; placebo)
• Percent change in body weight at 104 weeks: -25.7% (-30.6 kg; -67.5 lbs; 4 mg to MTD); -28.7% (-35.6 kg; -78.4 lbs; 9 mg to MTD); -29.9% (-38.1 kg; -83.9 lbs; 12 mg to MTD) and -18.9% (-22.3 kg; -49.1 lbs; placebo to MTD)

The types of adverse events seen were generally consistent with trials of other incretin-based therapies. The most common adverse events among participants treated with retatrutide (4 mg, 9 mg, 12 mg, vs. placebo, respectively) were nausea (28.6%, 38.4% and 42.4% vs. 14.8%), diarrhea (25.2%, 34.1% and 32.0% vs. 13.5%), constipation (23.8%, 25.9% and 26.1% vs. 10.9%), vomiting (10.6%, 22.8% and 25.3% vs. 4.8%), and upper respiratory tract infection (14.2%, 12.2% and 13.1% vs. 11.6%). Incidences of dysesthesia occurred in 5.1%, 12.3%, and 12.5% of patients treated with retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 0.9% with placebo, and incidences of urinary tract infections occurred in 7.5%, 8.8%, and 8.4% of patients treated with retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 5.3% with placebo. Events of dysesthesia and urinary tract infections were generally mild to moderate, the majority resolved during treatment, and most participants continued taking retatrutide. Discontinuation rates due to adverse events were 4.1%, 6.9%, 11.3%, with retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 4.9% with placebo.

Additional TRIUMPH-1 results will be presented at the 86^th annual American Diabetes Association Scientific Sessions, along with other results from Lilly’s cardiometabolic pipeline. Additional detailed results will be presented at future medical meetings and published in peer-reviewed journals. More results from the TRIUMPH Phase 3 clinical trial program will be shared later this year, including data from TRIUMPH-2, which is evaluating retatrutide in adults with obesity or overweight and type 2 diabetes, and TRIUMPH-3, which is evaluating retatrutide in adults with obesity or overweight and established cardiovascular disease.

About retatrutide
Retatrutide is an investigational, once-weekly, triple hormone receptor agonist, which activates the body’s receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon. Lilly is studying retatrutide in several Phase 3 clinical trials to evaluate its potential efficacy and safety in obesity and overweight with at least one weight-related medical problem, type 2 diabetes, knee osteoarthritis pain, moderate-to-severe OSA, chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease. Retatrutide is an investigational molecule that is legally available only to participants in Lilly’s clinical trials.

About TRIUMPH-1 and the TRIUMPH clinical trial program

The initial TRIUMPH Phase 3 clinical development program is evaluating the safety and efficacy of retatrutide for the treatment of patients with obesity or overweight, moderate-to-severe OSA and obesity, and knee osteoarthritis pain across four global registrational trials. The program, which began in 2023, has enrolled more than 5,800 participants with additional results anticipated over the next year.

TRIUMPH‑1 (NCT05929066) is a Phase 3, 80‑week, randomized, double‑blind, placebo‑controlled master trial comparing the efficacy and safety of retatrutide with placebo in adults with obesity or overweight. TRIUMPH-1 included a master trial for obesity and two basket trials for knee osteoarthritis pain or moderate-to-severe obstructive sleep apnea. The study randomized 2,339 participants in a 1:1:1:1 ratio to receive either retatrutide 4 mg, 9 mg, 12 mg, or placebo. Participants randomized to retatrutide initiated treatment with 2 mg once weekly and increased the dose in a step-wise approach every four weeks until reaching the target dose of 4 mg (via one step at 2 mg), 9 mg (via steps at 2 mg, 4 mg and 6 mg) or 12 mg (via steps at 2 mg, 4 mg, 6 mg and 9 mg). TRIUMPH-1 included a pre-specified extension period of 104 weeks. The extension period enrolled 532 participants with BMI ≥35 at week 0 who completed the main 80-week study and tolerated their assigned dose of medication. Participants received retatrutide once weekly for an additional 24 weeks, including a blinded escalation to maximum tolerated dose (9 mg or 12 mg). Data described in this press release refer to the master trial and extension period; analyses of the two basket trials for knee osteoarthritis pain and moderate-to-severe obstructive sleep apnea will be released subsequently. 

Endnotes and References 

1. The proportion of participants achieving BMI <30 was a pre-specified analysis not controlled for multiplicity; the same endpoint among participants with a baseline BMI ≥40 was assessed post-hoc.
2. The pre-specified extension enrolled the first 532 participants from participating countries to complete Week 80 on study drug without discontinuation or permanent dose reduction, with BMI ≥35 at baseline and >22 at Week 80. Their follow-up continued for 24 additional weeks targeting the achievement of retatrutide MTD (9 or 12 mg once weekly), for up to 104 weeks total treatment. All original arms are eligible to preserve blinding.
3. The efficacy estimand represents efficacy had all randomized participants remained on study intervention (with possible dose interruptions and modifications) without initiating prohibited weight management treatments.
4. Courcoulas AP, Yanovski SZ, Bonds D, et al. Long-term outcomes of bariatric surgery: a National Institutes of Health symposium. JAMA Surg. 2014;149(12):1323-1329.
5. The treatment-regimen estimand represents the average treatment effect regardless of adherence to study intervention or initiation of prohibited weight management treatments.

New Endoscopic Procedure Replicated Bariatric Surgery Results

On May 19, Keyron announced via the journal Gut that its ForePass endoscopic metabolic bypass platform reproduced insulin sensitivity levels observed following biliopancreatic diversion (BPD) while substantially outperforming semaglutide (Ozempic/Wegovy) in weight control in a randomized preclinical study.

Widely regarded as the most metabolically effective and invasive bariatric surgery ever developed, BPD has been associated with diabetes remission rates approaching ~80% and total body weight loss approaching ~40–50% in humans (SOARD, 2024). However, only ~1% of eligible patients undergo bariatric surgery due to its highly invasive nature (ASMBS/IFSO, 2024).

At the same time, 92% of patients receiving semaglutide fail to achieve even 15% weight loss (NEJM, 2021), despite patients with severe obesity and advanced metabolic disease often requiring substantially greater weight loss to achieve disease reversal (Lancet Diabetes & Endocrinology, 2025).

ForePass produced profound improvements in insulin sensitivity and glucose regulation, with insulin sensitivity levels closely matching those previously observed following BPD surgery in humans and more than two-fold higher than in semaglutide-treated animals. During oral glucose tolerance testing, ForePass-treated animals demonstrated near-complete suppression of postprandial glucose excursions with substantially reduced insulin demand, consistent with restoration of insulin sensitivity.

ForePass also dramatically outperformed semaglutide in weight control, limiting weight gain by more than eight-fold versus semaglutide-treated animals (4.3% vs 36%) and more than 10-fold versus controls (4.3% vs 47%).

The study was led by Ivo Boskoski, MD, Professor of Digestive Endoscopy at Università Cattolica del Sacro Cuore and one of Europe’s leading gastrointestinal endoscopists. “This study demonstrates that ForePass reproduced metabolic effects typically associated only with highly invasive metabolic surgery through a minimally invasive and fully reversible endoscopic approach,” said Prof. Boskoski. “The magnitude of the insulin sensitivity improvements and glycaemic control observed in this model is remarkable.”

Giorgio Castagneto Gissey, PhD, Founder and CEO of Keyron, said: “ForePass was designed around a central concept in metabolic disease biology that the upper intestine plays a major role in insulin resistance and glucose regulation. These findings support the possibility that metabolic effects previously achievable only through highly invasive surgery may soon be achieved through a scalable, fully reversible endoscopic procedure that avoids lifelong drug dependency.”

Geltrude Mingrone, Professor of Diabetes at King’s College London, added: “For decades, BPD has demonstrated the metabolic impact of excluding the proximal intestine, but its invasiveness has limited adoption. ForePass is exciting because it seeks to reproduce these mechanisms through a minimally invasive, reversible endoscopic approach. The insulin-sensitivity improvements observed in this large-animal study support advancing toward human trials.”

The publication follows earlier peer-reviewed findings in Gut and Diabetes, Obesity and Metabolism demonstrating significant metabolic improvements, enhanced insulin sensitivity, favorable microbiome changes, and superior weight control versus semaglutide in preclinical models.

Unlike bariatric surgery, ForePass is designed to be incision-free, fully reversible, and deployable through a short outpatient endoscopic procedure, potentially expanding access to surgery-level metabolic intervention for tens of millions of patients with severe obesity and metabolic disease too advanced for drugs and unwilling or unable to undergo major surgery.

Based on these findings, ForePass is advancing toward first-in-human clinical studies targeting severe obesity and metabolic disease.

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