{"id":1831,"date":"2024-12-21T11:47:17","date_gmt":"2024-12-21T11:47:17","guid":{"rendered":"https:\/\/retirednurseblog.com\/index.php\/2024\/12\/21\/an-experimental-drug-drove-people-to-lose-23-of-their-body-weight-its-still-seen-as-a-disappointment\/"},"modified":"2024-12-21T11:47:17","modified_gmt":"2024-12-21T11:47:17","slug":"an-experimental-drug-drove-people-to-lose-23-of-their-body-weight-its-still-seen-as-a-disappointment","status":"publish","type":"post","link":"https:\/\/retirednurseblog.com\/index.php\/2024\/12\/21\/an-experimental-drug-drove-people-to-lose-23-of-their-body-weight-its-still-seen-as-a-disappointment\/","title":{"rendered":"An experimental drug drove people to lose 23% of their body weight. It\u2019s still seen as a disappointment"},"content":{"rendered":"

Since Ozempic blasted onto the stage in 2017 with its approval for type 2 diabetes, drugmakers Novo Nordisk and Eli Lilly have been battling to leapfrog each other with newer and more effective medicines to turbo-charge diabetes and weight-loss results with the class known as GLP-1 receptor agonists. <\/p>\n

Novo Nordisk\u2019s latest attempt in weight loss, a combination drug called CagriSema, matched the bar set by Lilly\u2019s currently approved medicine, Zepbound, but didn\u2019t cleanly surpass it in late-stage clinical trial findings reported Friday. <\/p>\n

The experimental drug puts semaglutide, the ingredient in Ozempic and the weight-loss drug Wegovy, together with a medicine called cagrilintide to make the combination Novo Nordisk calls CagriSema. <\/p>\n

The 68-week study showed participants on CagriSema lost about 23% of their body weight, compared with 12% for those taking cagrilintide by itself, 16% for those on semaglutide, and 2.3% for people on a placebo. <\/p>\n

That means the study met its main goal, but those watching the weight-loss drug race closely had pegged their hopes on an average result for CagriSema of at least 25% weight loss, which would set a new bar for a field that\u2019s already been revolutionized by GLP-1 drugs. <\/p>\n

Lilly\u2019s Zepbound, approved in November 2023 as the Indiana-based drug giant\u2019s answer to Novo Nordisk\u2019s Wegovy, showed 21% average weight loss after 72 weeks for its highest dose in its Phase 3 trial, and a mid-stage study of another Lilly experimental medicine, called retatrutide, showed 24% weight loss after just 48 weeks. <\/p>\n

\u201cWe are encouraged by the weight loss profile of CagriSema demonstrating superiority over both semaglutide and cagrilintide in monotherapy,\u201d Martin Holst Lange, executive vice president for development at Novo Nordisk, said in a company news release Friday. He said Novo Nordisk would use insights from the trial \u201cto further explore the additional weight loss potential of CagriSema.\u201d <\/p>\n

Novo Nordisk\u2019s stock fell about 19% in early Friday trading on the news, wiping out tens of billions of dollars from the Danish drug giant\u2019s market value. <\/p>\n

CagriSema\u2019s side effects appeared to be similar to other drugs in the GLP-1 class; the company said the most common ones were gastrointestinal, with the \u201cvast majority\u201d mild to moderate and going away over time. Only just more than half of participants got up to the highest dose of the drug, though, leading some to question if the combination may not be as tolerable at high doses. <\/p>\n

Novo Nordisk said it expects results from a second Phase 3 trial of the medicine, this one in people with type 2 diabetes, in the first half of 2025. <\/p>\n

The study reported Friday, which Novo Nordisk calls REDEFINE 1, enrolled people with obesity or who are overweight and have at least one health condition \u2013 the same group for whom Wegovy and Zepbound are approved for weight loss. Participants\u2019 average body weight to start was 106.9 kilograms, or about 236 pounds. <\/p>\n

A medical \u2018arms race\u2019<\/h2>\n

Novo Nordisk\u2019s Ozempic and Wegovy are based on the active ingredient semaglutide, which mimics a hormone known as GLP-1 that\u2019s important for insulin secretion, digestion and appetite. Wegovy was approved by the FDA in 2021, after showing it helped people lose about 15% of their body weight, on average, in a 68-week clinical trial. <\/p>\n

Lilly answered with Mounjaro and Zepbound, approved in 2022 and 2023 for diabetes and weight loss, respectively. They use the active ingredient tirzepatide, which mimics not just GLP-1 but another hormone called GIP, to soup up results. <\/p>\n

A Lilly-sponsored head-to-head trial earlier in December reinforced findings from separate studies that Zepbound yielded greater weight loss over 72 weeks, on average, than Wegovy \u2014 20% compared with about 14%. <\/p>\n

The competition has also been a benefit to the drugmakers and their investors; Lilly\u2019s market value now surpasses $700 billion, quintupling over the last five years as GLP-1 drugs rake in billions of dollars in annual revenue. Novo Nordisk\u2019s stock tripled in that period, to more than $300 billion. <\/p>\n

Practitioners point out the field is moving at an incredible pace. <\/p>\n

A previous crop of weight-loss drugs, like Qsymia, a combination of older medicines not part of the GLP-1 class, and liraglutide, an earlier GLP-1 medicine sold under the brand name Saxenda, produced maximum weight loss of 8 to 11%, on average, said Yale School of Medicine\u2019s Dr. Jorge Moreno. <\/p>\n

Weight loss of 25%, Moreno and Grunvald noted, would reach results obtained by bariatric surgery. And in Novo Nordisk\u2019s CagriSema trial, 40% of participants did lose at least 25% of their body weight \u2013 just not enough to bump the trial\u2019s overall average result past that benchmark. <\/p>\n

\u201cFive years ago, if you\u2019d said, \u2018Novo Nordisk is going to have a new drug [where] 40% of people will get 25% weight loss, but that\u2019ll be pretty disappointing in 2024,\u2019 we would have said, \u2018You\u2019re smoking something, right?\u2019\u201d said Dr. Daniel Drucker, a pioneer of research into GLP-1 at the University of Toronto, who\u2019s worked with companies developing these medicines. <\/p>\n

Even if next-generation medicines show greater degrees of weight loss, Drucker said, it takes several years for trials to prove benefits on other outcomes like those, which may be more meaningful to patients and doctors. <\/p>\n

Competition through combination<\/h2>\n

With CagriSema, Novo Nordisk is targeting an additional hormone called amylin, in addition to GLP-1. Lilly\u2019s retatrutide builds on tirzepatide\u2019s GLP-1 and GIP by adding yet another hormone target, glucagon \u2013 giving it the moniker \u201cTriple G.\u201d <\/p>\n

Another drug company, Amgen, has taken yet another approach, blocking GIP instead of activating it, as tirzepatide does; its drug, dubbed MariTide, produced about 20% weight loss, on average, over the course of a year in mid-stage trial results reported in November. <\/p>\n

The medicine is designed to be administered less frequently than Wegovy and Zepbound \u2013 with injections once a month or less, compared with current drugs\u2019 weekly shots. Still, the results led investors to sell Amgen\u2019s stock over fears it wouldn\u2019t be able to catch up with competitors. <\/p>\n

\u201cIt just shows you how fast the field is moving and how high the expectations are moving,\u201d said Drucker. <\/p>\n

The signal that targeting amylin could preserve lean mass during weight loss \u2014 a key question about GLP-1 drugs \u2014 has so far been from animal studies, Drucker pointed out, leading him to question whether that result would bear out in human studies. <\/p>\n

But he noted yet another hormone, glucagon, which is the third addition to Lilly\u2019s retatrutide, \u201cis very good at getting fat out of the liver,\u201d so it may be especially helpful for people with metabolic liver disease. <\/p>\n

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