GLP-1 drugs could open a new frontier in NASH treatment

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This morning, Eli Lilly reported positive phase 2 results for its dual GLP-1 and GIP receptor agonist tirzepatide in patients with nonalcoholic steatohepatitis (NASH). In the SYNERGY-NASH trial, the therapy achieved NASH resolution without worsening fibrosis in 61.3% of patients. That is considerably higher than data for semaglutide.

Picturing tirzepatide’s NASH resolution in a phase 2 study

The bar graph below depicts the proportion of participants showing no worsening of liver fibrosis at 52 weeks with varying doses of tirzepatide compared to a placebo in the SYNERGY-NASH phase 2 study. See page 17 here for the data source.

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Zepbound helps people lose 25% of body weight on average 88 weeks, but weight regain is a concern

Lilly’s hot weight loss drug Zepbound (tirzepatide) may be one of the most effective drug therapies for weight loss. In an open-label 36-week study, participants lost an average of 20.9% of their body weight in 36 weeks. With an average weight of 107.3 kg (236.5 lbs), that equates to about 22.4 kg (49.4 lbs) on average.

Weight regain a risk for those going off Zepbound

The catch, however, is that participants needed to keep taking the drug to keep losing weight. Those who stopped taking it saw a rebound, regaining about half of what was lost in the 52-week period after the initial 36-week study. But those who kept taking tirzepatide continued losing weight — an additional 5.5% reduction from week 36 to week 88.

In general, significant weight loss followed be regain can be more than an inconvenience. A Journal of Clinical Endocrinology and Metabolism 16-year prospective cohort study looking at patients with type 2 diabetes found such fluctuations to be linked to…

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Tirzepatide beats semaglutide 3-to-1 for weight loss goals in real-world data

A new real-world study (pre-print) is the first to directly compare weight loss outcomes between the popular diabetes medications Lilly’s Mounjaro (tirzepatide) and Novo Nordisk’s Ozempic (semaglutide). The results show Mounjaro users are significantly more likely to achieve meaningful weight loss.

Analyzing data from more than 40,000 patients from a large U.S. health database, the researchers found those taking Mounjaro were nearly three times more likely to lose 10% of their body weight compared to Ozempic users. Additionally, they were also almost twice as likely to lose 5% of their weight, and three times more likely to lose 15%.

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Lilly’s Zepbound to enter the weight management market with competitive pricing

Lilly’s tirzepatide notched an FDA approval for chronic weight management, potentially clearly the way for billions in additional sales. Analysts have projected that the drug could fetch $26 billion in annual sales by 2030, with roughly two-thirds of that sum related to obesity​ treatment​. Bank of America analyst Geoff Meacham is even more optimistic, predicting that sales could hit $48 billion annually​.

The company is calling the obesity-branded version of the drug Zepbound, in contrast to Mounjaro, which won FDA approval for type 2 diabetes on May 13, 2022.  

Lily’s stock was up 3.20% to $619.13. Year-to-date, its share price is up almost 70%, in part as a result of strong sales prospects for tirzepatide. 

The table below outlines the starting cash prices for a range of GLP-1 receptor agonists. Lilly’s Zepbound, the obesity-branded version of tirzepatide, has a competitive starting price in the segment. With insurance, Zepbound could cost as lo…

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GLP-1 drug tirzepatide shines in SURMOUNT-3 trial with weight loss of 26.6%

In the phase 3 SURMOUNT-3 trial, tirzepatide recipients saw some of the most impressive weight loss results among trials of GLP-1 drugs, including most notably semaglutide. In the study, participants’ total mean weight loss was 26.6% over 84 weeks following a 12-week intensive lifestyle intervention and subsequent tirzepatide treatment. In all, participants who received tirzepatide lost an additional 18.4% of their body weight compared to a weight gain of 2.5% in the placebo group.

In SURMOUNT-3, some 87.5% of participants who received tirzepatide achieved an additional weight reduction of 5% or more, compared to 16.5% of those in the placebo group.

While it is difficult to compare data from separate studies, the highest weight loss percentage for tizepatide, 26.6%, was 53% higher than the highest percentage, 17.4%, for semaglutide (OASIS 1).

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Tirzepatide versus semaglutide: Which contender will prevail in the battle against obesity and type 2 diabetes?

Eli Lilly‘s (NYSE:LLY) tirzepatide achieved up to 15.7% weight loss in the SURMOUNT-2 study, sparking a potential tirzepatide vs semaglutide competition in the obesity and type 2 diabetes treatment markets. The phase 3 study enrolled 938 participants with diverse backgrounds.

Tirzepatide promises to be a megablockbuster with a number of analysts pegging peak annual sales hitting $25 billion. Few drugs have surpassed the $20 billion threshold. One notable example is AbbVie’s monoclonal antibody Humira (adalimumab), which hit $21.2 billion in sales in 2022 and $20.7 billion a year earlier. The drug was the world’s bestseller until the COVID-19 pandemic stoked demand for the Pfizer-BioNTech vaccine, whose cumulative annual sales hit $59.1 billion in 2021.

Lilly has signaled its plans to submit tirzepatide to the FDA, potentially leading to competition between tirzepatide and semaglutide in the obesity and type 2 diabetes treatment markets.

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Lilly’s tirzepatide wins FDA approval for type 2 diabetes

FDA has approved Mounjaro (tirzepatide), the first glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) for treating adults with type 2 diabetes.

Developed by Eli and Co., tirzepatide could quickly become a mega-blockbuster. According to Mizuho Securities, annual sales of the drug could approach $14 billion by 2030.

To win approval, Lilly provided data from the Phase 3 SURPASS clinical studies showing that it supported superior A1C reductions than all comparators, including insulin glargine and insulin degludec. The SURPASS trials also pitted tirzepatide against metformin, SGLT2 inhibitors and sulfonylureas.

The drug also has the side benefit of supporting weight loss, although it is not indicated for obesity. Volunteers in the SURPASS trials lost an average of 12 and 25 lb., depending on dose level.

In the SURMOUNT-1 study, the drug yielded up to 22.5% in adults with obesity or overweight.

Lilly will marke…

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Lilly’s tirzepatide gives Novo Nordisk’s semaglutide a run for the money in Phase 3 trial

Eli Lilly and Co. (NYSE: LLY) has announced that tirzepatide enabled trial participants to lose up to 22.5% of their body weight in the SURMOUNT-1 study.

Study volunteers receiving tirzepatide lost up to 52 lb. (24 kg) in the 72-week Phase 3 trial. A total of 55% of those receiving a 10 mg dose lost at least 20% of their body weight while 63% of those on a 15 mg dose hit the same benchmark. Only 1.3% of those taking placebo had the same level of weight loss.

Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor antagonist.

It is thus broadly similar to Novo Nordisk’s semaglutide, a glucagon-like peptide 1 (GLP-1) receptor antagonist that has achieved strong growth in diabetes as Rybelsus. Demand appeared to be strong for Wegovy, an injectable semaglutide formulation that won FDA approval for supporting weight management in June 2021, but the drug has faced supply challenges in the U.S. Read more

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Regeneron uncovers genetic mutations that guard against obesity

Regeneron Pharmaceuticals (NSDQ:REGN) has announced that its Regeneron Genetics Center (RGC) has discovered rare genetic mutations associated with protection against obesity.

RGC researchers learned that people with at least one inactive copy of the GPR75 gene tend to weigh about 12 pounds less than those without that mutation. In addition, those individuals faced a 54% reduced risk of obesity.

The center made the finding after sequencing 640,00 exomes, which are part of the genome composed of exons.

A study published in Science that summarized the findings concluded that inhibiting “GPR75 may be a therapeutic strategy for obesity.”

Regeneron is working with partners such as Alnylam Pharmaceuticals to develop drug candidates that mimic the genetically afforded protection.

The mutations were only present in roughly one out of every 3,000 people. Some 645,000 volunteers from the U.K., U.S. and Mexico, participated in the study.


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Lilly’s tirzepatide bests semaglutide in type 2 diabetes trial 

Eli Lilly (NYSE:LLY) has announced that its investigational drug tirzepatide led to more substantial blood glucose and body weight improvements in a Phase 3 trial than semaglutide, a diabetes drug from Novo Nordisk (NYSE:NVO) that recently scored FDA approval for weight loss in early June.

Lilly’s SURPASS-2 results published in The New England Journal of Medicine show tirzepatide achieved superior A1C and body weight reductions compared to injectable semaglutide in adults with type 2 diabetes.

A JAMA opinion article recently posited that semaglutide could lead to a ‘new dawn’ for obesity treatment.

The Lilly trial randomly assigned patients to receive tirzepatide at doses of 5 mg, 10 mg, or 15 mg or a 1-mg dose of semaglutide.

Semaglutide is a glucagon-like peptide 1 receptor agonist. Conversely, tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist.

In the 40-week SURPASS-2 trial, i…

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FDA approves Novo Nordisk’s semaglutide for weight management

FDA has approved Wegovy, the weekly semaglutide treatment for obesity from Novo Nordisk (CPH:NOVO-B).

The agency approved the use of semaglutide for type 2 diabetes in 2017. FDA approved an oral formulation for diabetes in 2019.

Semaglutide is a glucagon-like peptide (GLP-1) receptor agonist (RA) that continues to find wider use.

In clinical trials, Novo Nordisk people led to an average weight loss of 15% to 18% of body weight over 68 weeks in patients with obesity without diabetes.

In a clinical trial published in JAMA and The New England Journal of Medicine, semaglutide tripled weight loss for participants who received lifestyle management coaching.

Novo Nordisk continues to research new potential uses of the drug. It has launched clinical trials to test its use for conditions ranging from atherosclerosis to Alzheimer’s and Parkinson’s disease. A posthoc analysis involving three cardiovascular clinical trials found that participants recei…

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Why Lilly’s tirzepatide has blockbuster potential 

Tirzepatide from Eli Lilly (NYSE:LLY) continues to show promise for diabetes, outperforming popular diabetes drugs in head-to-head clinical trials, according to GlobalData. 

In the recent SURPASS-4 study, tirzepatide supported the reduction of hemoglobin A1C (HbA1c) in people with type 2 diabetes while also supporting weight loss. The study pitted tirzepatide against insulin glargine. 

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA). 

The experimental drug also bested the injectable anti-diabetes drug semaglutide in the SURPASS-2 trial. Semaglutide from Novo Nordisk (NYSE:NVO) is currently FDA indicated as a treatment for type 2 diabetes. Semaglutide also supported substantial weight loss in a recent clinical trial, potentially supporting its use as an obesity treatment. Semaglutide is also a GLP-1 receptor agonist.  

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