Surpassing Semaglutide? The new generation of weight loss drugs is going crazy with fat reduction, muscle gain, uric acid reduction, and oral administration

Nowadays, when it comes to star drugs, who doesn't know about the "weight loss injection"?

At the recently concluded American Diabetes Association annual meeting (2025 ADA), major weight loss giants showcased their offerings, taking turns to present.

This peak showdown among experts is merely a microcosm of the explosive growth in the weight loss sector in recent years. Competitors diving into this red ocean are increasing at an exponential rate—pharmaceutical companies without several GLP-1 pipelines are hesitant to even greet other innovative drug companies.

However, those in the red ocean also know that the development bottleneck for weight loss drugs has already begun to emerge.

GLP-1, the momentum is slowing down

Semaglutide, liraglutide, terzepatide... In recent years, GLP-1 receptor agonists have become the most popular star drugs worldwide.

Taking semaglutide as an example, its revenue reached $21.2 billion in 2023, with the weight loss version Wegovy surging 407% to $4.6 billion. Last month, semaglutide officially surpassed the K drug, claiming the title of "king of drugs" globally.

The emergence of GLP-1 drugs has completely transformed the weight loss market—just by taking medication, one can achieve weight loss results comparable to surgical procedures.

In 2024, the weight loss duo of semaglutide and terzepatide is expected to generate a combined sales revenue of $13.37 billion. Several institutions have predicted that by 2030, the annual sales of GLP-1 receptor agonists will exceed $100 to $150 billion [1].

Amidst this phenomenal popularity, countless latecomers have rushed into the market. As this track gradually develops towards the direction of Guangzhou Metro Line 3, pharmaceutical companies struggling in the red ocean have begun to realize one thing:

The story of weight loss drugs can no longer rely solely on data.

Image source: Weibo

CagriSema should have a deep understanding of this.

During the recent 2025 ADA, Novo Nordisk announced the complete data from two Phase III clinical trials of its new weight loss drug CagriSema.

The results showed that CagriSema led to an average weight loss of up to -22.7%. Although the Executive Vice President of Development stated that "more than half of the participants did not reach the maximum dose, and the average weight loss of 22.7% could be further improved," the market's reaction was still somewhat lukewarm—company shares fell nearly 4% in pre-market trading.

According to previous conference call records from Novo Nordisk, management originally hoped that this dual-target drug would achieve about a 25% weight loss effect during the trial, surpassing terzepatide's 21%. Surveys also indicated that investors initially expected the dual-target weight loss effect to reach as high as 27%.

The greater the expectation, the greater the disappointment. When once-dominant experts begin to fiercely compete within the 20-30% range for that half-step, it may indicate that the data ceiling for GLP-1 monotherapy has indeed emerged On the other hand, the first batch of patients using weight loss drugs has already begun to stop their medication.

An industry analysis shows that among American patients who started taking GLP-1 drugs in 2021, about 2/3 did not stick with it for a year.[12]

Nature pointed out in a report that the most common reasons for prematurely stopping weight loss medications are mistaking a weight plateau for "tolerance" to the drug and being intolerant to mild side effects such as gastrointestinal issues [5].

From a fundamental perspective, the mechanism of action of GLP-1 drugs overlaps significantly with the mechanism of side effects, which also means that issues like "nausea and vomiting" are "locked" to the dosage of the medication. Patients with severe individual differences may be deterred by side effects before they even see any effects.

Moreover, one year after stopping the medication, many people regain about two-thirds of the weight they lost [2]. Waist circumference (abdominal fat), as well as blood pressure, blood sugar, and cholesterol levels, may also rebound [2,3].

Source: Literature 3

Another more serious issue is the loss of muscle mass while losing weight. Research indicates that nearly 40% of the weight lost by users is "lean body mass," which is primarily composed of muscle mass. This leads to a decrease in basal metabolic rate and increases the risk of cardiovascular diseases, osteoporosis, and other conditions.

Despite the various factors, although the weight loss drug market still has enormous potential, it does not prevent the homogenization competition in the GLP-1 sector from becoming increasingly severe.

GLP-1 has started to stagnate; if weight loss drugs want to stand out, they need to tell a new story.

Muscle gain, oral administration, uric acid reduction… who is the true "next generation"?

Pharmaceutical companies struggling in the red sea clearly understand this issue better than we do.

But where should the new story begin? There must be a solution within three steps— the weaknesses of old stars are the best breakthrough points.

The data ceiling, side effect issues, muscle loss… the bottlenecks of GLP-1 drugs we mentioned earlier have long been identified by major pharmaceutical companies.

First, the weight loss giants Eli Lilly and Novo Nordisk are once again collaborating on a dual-target approach with insulin analogs.

The aforementioned Novo Nordisk CagriSema is a GLP-1 + insulin dual-target combination injection formulation. Although the process has had some twists and turns, the future plans are already very clear. Novo Nordisk has stated that it will submit a marketing application for CagriSema to the FDA in early 2026, with an expected market launch in early 2027.

Novo Nordisk official website screenshot

At the same time, Eli Lilly recently announced the latest data on the insulin analog Eloralintide at the 2025 ADA: in a 12-week Phase 1 clinical study, the average weight loss in the highest dose group was 11.3%, while the low dose group averaged a weight loss of 2.6%, indicating better gastrointestinal tolerance [9].

Although still in Phase 1, some analyses have rated this result as "particularly impressive," undoubtedly hoping for further exploration of this drug in combination with Tirzepatide.

On the other hand, the oral small molecule sector is becoming increasingly competitive.

Semaglutide has once again claimed a "first title" earlier this year — the world's first oral weight loss GLP-1 drug to submit a marketing application. From the data, it shows a 17.4% weight loss over 68 weeks, with weight loss effects comparable to injection forms, while being more convenient and quicker to take orally.

Eli Lilly's oral small molecule Orforglipron is also not to be outdone, planning to submit a weight loss application by the end of this year and a diabetes application next year, aiming for a curveball overtaking.

With both giants entering the field, many commentators have high expectations for the upcoming "oral weight loss era."

Source: Screenshot from "Initial D"

Next is "fat loss and muscle gain."

This term has only gained popularity over the past year, with new drugs emerging globally, mainly targeting the activation of the activin receptor pathway that regulates skeletal muscle growth signals, including ActRII receptors, the ligand protein myostatin (MTSN), and activin A.

For example, Eli Lilly, which already holds Tirzepatide, made a significant investment of $1.925 billion to acquire Versanis in July 2023, securing its core product ActRIIA/B monoclonal antibody Bimagrumab. This drug was initially developed by Novartis for the treatment of pathological muscle loss and weakness but was discontinued due to clinical failure.

However, while one door closes, another opens; Versanis later acquired the drug from Novartis and continued to develop its weight loss indications. According to its clinical research results, after 48 weeks of treatment with Bimagrumab, patients' total body fat content decreased by an average of 20.5%, while muscle mass increased by 3.6% [6].

Source: Literature 6

There is also the selective muscle suppressor activin blocking antibody Apitegromab from the American biotechnology company Scholar Rock, which, in a Phase 2 study for treating obesity, was used in combination with Tirzepatide, retaining an additional 54.9% of lean body mass. This has attracted widespread attention.[13] Among domestic pharmaceutical companies, the Act RIIA monoclonal antibody from Laika Pharmaceutical is also moving towards a "fat reduction and muscle preservation" strategy. Last year, it announced a clinical cooperation agreement with Eli Lilly, and the results of the combined study with GLP-1 are expected soon.[14]

In addition, the recently approved Masitide peptide has opened up a new track. As the world's first and only approved GCG/GLP-1 dual receptor agonist, it not only shows an average weight loss of 14% and an average reduction in blood sugar of 2.15%, but also demonstrates advantages in lowering uric acid and reducing liver fat.

Screenshot from the National Medical Products Administration website

In the increasingly fierce competition for weight loss drugs, whether related to GLP-1 or innovative drugs with entirely new mechanisms, mechanisms are continuously emerging, data is piling up, and claims are endless. Everyone is striving to earn the title of "next-generation weight loss drug."

However, the era of crushing competitors with data and the era of the stock market responding to every call are long gone.

The market for weight loss drugs remains vast, and the bottlenecks also signal opportunities. But who will be the "true game changer"?

The answer is not found in the data tables of papers, nor in the PPTs and posters of conferences; it can only be found after crossing clinical trials and truly entering the market, where the answer lies in the real feedback from the market.

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