The global obesity problem is getting worse, with over 1 billion people affected in 2022. The number of obese adults and children has increased significantly, and it's expected to rise to over 4 billion by 2035. The weight loss drug market has great potential, growing from $1.8 billion in 2016 to $2.6 billion in 2020, with predictions of reaching $6.3 billion by 2025. In response to high demand, pharmaceutical companies are expanding production and seeking new uses for their drugs, but competition is growing as many companies enter the market. Next, we will focus on the latest clinical data for obesity drugs and provide a comprehensive overview of available weight loss medications.

Latest Clinical Data on Weight Loss Drugs

Metsera - MET-097

Om September 24, 2024, Metsera announced that its long-acting weight loss therapy, MET-097, achieved significant and lasting weight loss effects in a phase 1 clinical trial. Participants experienced a 7.5% weight loss by day 36 of treatment, and the drug's pharmacokinetic profile supports a potential monthly dosing regimen. Metsera plans to launch a phase 2b clinical trial for MET-097 in the fourth quarter of 2024, with data expected in the first half of 2025.

MET-097 is an investigational long-acting subcutaneous GLP-1 receptor agonist developed using Metsera's proprietary HALO peptide lipidation platform technology, featuring an extended clearance time in the body.

Viking—VK2735

On Feb 27, 2024, Viking announced its GLP-1/GIP receptor agonist VK2735 met primary and secondary endpoints in the Phase II obesity trial. Patients receiving weekly doses of VK2735 demonstrated statistically significant reductions in mean body weight after 13 weeks, ranging up to 14.7% from baseline. Throughout the study, weight loss was gradual, with no plateau observed at 13 weeks, and the drug was found to be safe and well-tolerated (see Figure 1).

Figure 1. Observed Change in Body Weight Following 13 Weeks of Once-Weekly Dosing with VK2735 [2]

Viking has received written feedback from the FDA, allowing them to advance VK2735 to phase 3 clinical trials. Additionally, VK2735 in oral tablet form showed good safety and tolerance, along with promising clinical effects in a phase 1 study. Viking plans to start the phase 2 trial for this project in the fourth quarter of this year.

Amgen—AMG 133

Amgen's weight loss drug, AMG 133 (MariTide), shows promise in helping both animals and people lose weight without serious side effects, according to new data from the company. Unlike other options, it may only need to be taken once a month and might not require lifelong use.

In a study published in Nature Metabolism on February 5, Amgen shared results showing that a single injection of AMG 133 reduced weight and improved metabolic markers in obese mice and monkeys. A similar study in humans found that participants in a phase 1 trial lost weight and maintained that loss for about five months after their last dose.

In the multiple-dose part of the trial, participants who received a 140 mg dose of AMG 133 lost an average of 7.4% of their body weight by Day 78 after three doses. Those taking a higher dose of 420 mg lost nearly 5% by Day 7 and 14.5% by Day 85. Participants in all three dosing groups maintained some weight loss for up to 70 days after their last dose, with the highest dose group retaining up to 11.2% of their weight loss.

Figure 2. AMG 133 exhibited GIPR antagonist and GLP-1R agonist activities in vitro and extended PK profiles. [3]

Latest Developments in Oral Weight Loss Drugs

Novo Nordisk—Amycretin

On September 11, 2024, Novo Nordisk presented the first phase 1 study results for the oral weight loss drug Amycretin (NN9487) at the European Association for the Study of Diabetes (EASD) annual meeting.

Amycretin is a GLP-1 receptor/amylin receptor (GLP-1R/AMYR) agonist, with a subcutaneous form (NN9490) given weekly and the oral version taken daily.

The results showed that after 12 weeks, participants in the 50 mg and 100 mg groups lost an average of 10.4% and 13.1% of their body weight, respectively, compared to just 1.1% in the placebo group. Notably, the weight loss had not plateaued, suggesting that patients may achieve even more weight loss with extended treatment.

Figure 3.  Weight loss effects of Amycretin in the phase 1 trial. [4]

Roche—CT-996

On July 17, 2024, Roche announced positive results from its phase 1 clinical trial of the oral weight loss small molecule CT-996. The data showed that after four weeks of treatment, obese participants without type 2 diabetes in the CT-996 group lost an average of 7.3% of their body weight, compared to just 1.2% in the placebo group. The difference between the two groups was clinically significant (6.1% difference, p<0.001).

FDA-Approved Popular Weight Loss Drug

Tirzepatide (Zepbound)

On November 8, 2023, the FDA approved Eli Lilly's Tirzepatide (Zepbound) for weight loss. Zepbound is administered via weekly injections, with doses gradually increasing over 4 to 20 weeks. It is the world’s first dual-target agonist, working by activating two naturally occurring hormones: GLP-1 and GIP. This helps slow gastric emptying, prolong feelings of fullness, and reduce hunger signals in the brain.

Recent developments show that Tirzepatide demonstrated significant weight loss effects in the SURMOUNT-3 and SURMOUNT-4 trials.

In SURMOUNT-3, after a 12-week lifestyle intervention (including a low-calorie diet and exercise), participants treated with Tirzepatide lost an average of 21.1% of their body weight, while the placebo group saw a weight increase of 3.3%. Over 84 weeks, the average weight loss reached 26.6% compared to baseline.

The SURMOUNT-4 results, published in JAMA Network in December 2023, indicated that Tirzepatide reduced the average weight of overweight (non-diabetic) or obese adults by 20.9% after 36 weeks. However, weight rebounded significantly after stopping the drug; participants switching to a placebo after week 36 gained back 14% of their weight, while those continuing treatment maintained their weight loss.

Semaglutide (Wegovy)

Semaglutide, developed by Novo Nordisk, is a long-acting GLP-1 analog that shares 94% of its amino acid sequence with natural GLP-1, functioning as a GLP-1 receptor agonist. It activates GLP-1 receptors to stimulate insulin secretion, delay gastric emptying, and suppress appetite, leading to reduced food intake and lower blood sugar levels.

Wegovy was approved by the FDA in 2021 for chronic weight management in adults with obesity or overweight. In March 2023, the FDA expanded its approval to include reducing the risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease who are also obese or overweight. It is administered once a week.

In May 2023, Novo Nordisk released results from its phase III OASIS 1 study, showing significant and sustained weight loss effects. Specifically, in the group receiving 50 mg of semaglutide, participants lost an average of 17.4% of their body weight, compared to 1.8% in the placebo group. Additionally, 89.2% of those on semaglutide maintained a weight loss of at least 5% after 68 weeks, compared to 24.5% in the placebo group. Based on treatment policy evaluations (regardless of adherence), the semaglutide group still showed a weight loss of 15.1% versus 2.4% in the placebo group, with 84.9% achieving a 5% weight loss compared to 25.8% in the placebo group.

References:
[1] Metsera Reports Highly Competitive Results from Ongoing Trial of Novel, Potential OnceMonthly Injectable GLP-1 Receptor Agonist MET-097
[2] Viking Therapeutics Announces Positive Top-Line Results from Phase 2 VENTURE Trial of Dual GLP-1/GIP Receptor Agonist VK2735 in Patients with Obesity
[3] A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings
[4] Safety, tolerability and weight reduction findings of oral amycretin: a novel amylin and glucagon-like peptide-1 receptor co-agonist, in a first-in-human study.
[5] Ad hoc announcement pursuant to Art. 53 LR] Roche announces positive Phase I results of its oral GLP-1 receptor agonist CT-996 for the treatment of people with obesity.
[6] Wadden, T.A., Chao, A.M., Machineni, S. et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med 29, 2909–2918 (2023). https://doi.org/10.1038/s41591-023-02597-w
[7] Aronne LJ, Sattar N, Horn DB, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024;331(1):38–48. doi:10.1001/jama.2023.24945
[8] Novo Nordisk A/S: Oral semaglutide 50 mg achieved 15.1% weight loss (17.4% if all people adhered to treatment) in adults with obesity or overweight in the OASIS 1 trial https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=166110