ADA: Lilly's weight-loss reveal, and wannabes display wares

Eli Lilly has revealed the data that has caused it to be so excited by triple G obesity therapy retatrutide, highlighting its broad benefits across weight loss and related conditions.

In May, Lilly reported that weekly injections of retatrutide achieved dramatic weight loss of up to 28.3% at 80 weeks in the TRIUMPH-1 study, compared to a 2.2% fall with placebo at 80 weeks, which compares favourably with its current weight-loss blockbuster Zepbound (tirzepatide) and is around the level that can be expected after bariatric surgery.

At ADA, it added colour to that top-line result, including that two-thirds (65.3%) of patients taking the GLP-1, GIP, and glucagon agonist had achieved a BMI below 30, taking them below the threshold for obesity.

Alongside the weight-loss result, however, were significant improvements in knee osteoarthritis pain, with an improvement of up to 73% on the WOMAC pain scale, and a 60.6% reduction in moderate-to-severe obstructive sleep apnoea using the AHI scale.

There were also "clear improvements" in cardiometabolic measures, with reductions in triglycerides, non-HDL cholesterol, and systolic blood pressure that lead study author Ania Jastreboff, of Yale University, said "meaningfully impacts the overall health of people living with obesity."

Lilly also presented the results of the TRANSCEND-T2D-1 of retatrutide in type 2 diabetes (T2D) – simultaneously published in The Lancet – which revealed significant improvement in blood glucose control with falls of 2.0% in the A1C biomarker at 40 weeks. That's an impressive result in such a short time, particularly as up to 46% of patients were in the normal range by the end of the follow-up period. Patients treated with the triple G also saw weight loss of up to 16.8%.

"Obesity drives more than 200 downstream diseases, yet, we have historically treated those conditions one at a time and in silos," Jastreboff told delegates at ADA. "The future of obesity treatment may not be a single-purpose drug, but a therapy that transforms multiple diseases at once."

Other obesity studies at ADA

Meanwhile, there was a series of other weight-loss and diabetes hopefuls with data on display at ADA, including new candidates from Zealand Pharma/Roche, Pfizer, Novo Nordisk, and Sciwind.

Zealand Pharma and Roche presented updated results from their ZUPREME-1 trial of petrelintide, a long-acting amylin analogue given as a weekly injection, pointing to "placebo-like tolerability" over 42 weeks and relatively modest weight reductions of up to 10.7%, alongside falls in waist circumference, triglycerides, and C-reactive protein, a biomarker for inflammation. Only 1.5% of participants discontinued petrelintide due to gastrointestinal side effects, potentially positioning the drug as a gentler alternative for patients who suffer serious GI side effects with other drugs, and raising the prospect of combination use.

Pfizer showcased injectable GLP-1 agonist berobenatide (PF-08653944/MET-097i), acquired as part of its $10 billion takeover of Metsera last year after its in-house projects failed. It presented data from the phase 2b VESPER-1 study that revealed a weight loss of 15.9% at 60 weeks with a weekly injection, and up to 12.4% with a monthly dose at week 28 in the VESPER-3 trial. In addition, data from the Phase 2b VESPER-2 study, which evaluated weekly dosing in people with obesity or overweight and T2D, showed a 2.2% reduction in A1C at week 28.

Novo Nordisk presented new data from the REIMAGINE programme of GLP-1/amylin combination CagriSema (cagrilintide and semaglutide) – already filed for obesity – in T2D. REIMAGINE-1 in adults with inadequately controlled T2D revealed a 1.8% reduction in A1C at week 40, with weight loss of 1.8%. REIMAGINE-3 compared CagriSema to placebo in T2D patients as an add-on to basal insulin with or without metformin, and showed improvements in A1c with a reduction from 8.8% to 6.5%, and weight reductions of up to 12%.

Finally, China's Sciwind pitched results of the SLIMMER-UP-SWITCH trial comparing its weekly injectable GLP-1 agonist ecnoglutide, already on the market in its home market, with Novo Nordisk's weekly injectable Wegovy (semaglutide), showing 35% greater weight loss at 20 weeks (12.8% versus 9.5%), along with a 20% improvement in waist circumference, while twice as many patients achieved 10% or greater weight loss. Pfizer has exclusive commercialisation rights for ecnoglutide in Mainland China.