This is probably the most challenging path in innovative drugs; the market is attractive, but the journey is tough, testing innovation potential.

Each New Drug Outperforms the Last; It Starts with a "Battle of the Gods"

Since the GLP-1 antidiabetic and weight-loss products—Novo Nordisk's "Semaglutide" and Eli Lilly's "Tirzepatide"—ignited the peptide field, it has meant that the starting point is already a "peak challenge." Subsequent competing products entering the market must either differentiate themselves or face these "god-tier opponents," initiating a "battle of the gods."

Indeed, on August 1, Innovent Biologics' new indication for "Mazdutide" was accepted for application, intended for the treatment of type 2 diabetes. Mazdutide is a GLP-1R/GCGR dual agonist, with its obesity indication application accepted this February, marking it as the world's first GLP-1R/GCGR dual agonist to apply for market approval.

Among the many yet-to-be-commercialized GLP-1 new drugs, "Mazdutide" is considered capable of competing with "Semaglutide." This product is one of the "multi-insurance packages" that Eli Lilly has in the antidiabetic and weight-loss market, developed in cooperation with the domestic innovative pharmaceutical company Innovent Biologics, making it a "potential star drug."

According to Insight database statistics, Mazdutide is undergoing five Phase III clinical studies. The most recent one, DREAMS-3, is a head-to-head Phase III clinical study comparing Mazdutide and Semaglutide in Chinese patients with type 2 diabetes and obesity, currently in progress.

Image source: Insight database

Clinical data for Mazdutide shows that after 24 weeks of treatment, a weight loss of over 15% compared to placebo and nearly 30 pounds was observed, marking the best in class for both percentage and absolute weight reduction.

Compared to the current hottest product in the weight-loss market, Novo Nordisk's Semaglutide, the 9mg dose of Mazdutide showed a weight reduction of 15.4%/14.7kg, while the 6mg dose showed a reduction of 12.6%/10.9kg.In contrast, Semaglutide showed an 8.0%/7.7kg reduction. Compared to Eli Lilly's Tirzepatide, the 9mg dose of Mazdutide also showed higher weight reduction percentages and absolute values than the 15mg high dose of Tirzepatide (-15.4% vs. -12.0%, -14.7kg vs. -13.0kg). In terms of safety, the most common adverse events during the treatment period were gastrointestinal-related, mostly mild or moderate and transient. The incidence of hypoglycemic events was low, with the majority being Grade 1 hypoglycemia and no severe hypoglycemic events reported.

The weight-loss indication application for "Mazdutide" is expected to be approved in the third quarter of 2025. This suggests that it is time for innovative pharmaceutical companies in the peptide field to accelerate their search for other breakthrough directions, given the high data threshold for "antidiabetic and weight-loss" products. There are more potential star drugs pushing the limits in this field, and more heavyweights are yet to come.

Competing Products Still in Clinical Trials Have Already Caused a Loss of Hundreds of Billions in Market Value for Eli Lilly and Novo Nordisk

Recently, Viking Therapeutics announced the advancement of its obesity therapy, the dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist VK2735, to a Phase 3 trial for its subcutaneous injection form, and a Phase 2 trial for its oral form. Notably, the VK2735 subcutaneous injection has skipped Phase 2b and moved directly to Phase 3. The impressive weight loss data from this product has directly led to a significant decline in the stock prices of Eli Lilly and Novo Nordisk in the last two weeks of July.Eli Lilly’s market value plunged by over $120 billion in one week, while Novo Nordisk saw a near 10% drop over eight trading days, with a market value loss of over $40 billion.

The media has commented that this not only astonished investors but also indicates an impending unprecedented transformation in the global weight-loss drug market.

Viking

According to the top-line data from a Phase 2 clinical trial (VENTURE) announced in the first quarter of this year, patients treated with a 15 mg dose of VK2735 subcutaneous injection once weekly for 13 weeks experienced a statistically significant weight loss of 14.7% (14.6 kg, approximately 29.2 lbs) from baseline. Throughout the study, patients continued to lose weight, and no plateau in weight loss was observed by the 13th week, suggesting the potential for even better weight loss outcomes thereafter.

Compared to Eli Lilly’s Tirzepatide, another GLP-1/GIP dual-target drug, which showed similar data at 12 weeks (indicated by an orange dashed line), VK2735's weight loss advantage is evident. It is also comparable to the 16-week data for CagriSema, Novo Nordisk's investigational new weight-loss drug, which demonstrated a 13% weight loss in Phase I clinical trials over 12 weeks.

Besides its efficacy, VK2735 also has a favorable safety profile. The discontinuation rate in the highest dose group (15 mg) did not exceed 20%. Regarding gastrointestinal adverse events (GI AEs), 95% were mild or moderate, mostly occurring early in the treatment, especially in the first week, and then gradually decreasing.

It’s worth noting that while both Eli Lilly and Novo Nordisk have "multi-product insurance packages" for antidiabetic and weight-loss solutions—Novo Nordisk evolving from Liraglutide to Semaglutide, and now developing the upgraded "CagriSema"—it will still take at least about three years for these new products to hit the market. Meanwhile, competitors are not only speeding up clinical trials but also achieving outstanding trial data. In these three years, it is enough time for several "god-tier products" to emerge in the market, further validating that the "battle of the gods" in the future of peptides is inevitable.

Novartis States It's Unwise to Enter the Market Now, While Pfizer Makes a Comeback

On July 18, during a Q2 earnings call, Novartis CEO Vas Narasimhan stated that the company had seriously considered whether it should enter the weight-loss drug market. Given the current state of GLP, GIP, and GIPR drugs, where Eli Lilly and Novo Nordisk have already excelled, Narasimhan concluded that it would not be "wise" for Novartis to enter the market with oral or injectable GLP or GIP products.

Novartis has instead shifted its focus and is now deeply invested in the nuclear medicine sector. Meanwhile, Pfizer, which has faced several setbacks in the diabetes and weight-loss field, is making another attempt. In mid-July, Pfizer announced the advancement of its oral GLP-1 drug into registrational trials, with the product showing a potential for nearly 10 pounds of weight loss over 16 weeks. (For more details, see: "Who is Pfizer's "weight loss opponent" to Lilly, Novo Nordisk? Slowing down mergers does not stop Pfizer's pursuit of weight loss assets...")

Pfizer's "relaunch" in the weight-loss sector highlights the pharmaceutical industry's optimism about the multi-billion-dollar market for diabetes and weight-loss drugs. While the potential is vast, it is also one of the most challenging fields—starting with a decisive battle and needing to accelerate right from the start.

Facing god-tier opponents, the most pressured are the peptide-based innovative pharmaceutical companies already in the market. As mentioned above, they shouldn't just focus on competing in diabetes and weight-loss data but should also seek other breakthrough directions. After all, competitors are not only excelling but also expanding their reach—recently, Semaglutide received approvals in the UK and EU for new indications, including reducing cardiovascular death, non-fatal heart attacks (myocardial infarctions), or strokes in overweight or obese adults with cardiovascular disease. Currently, Semaglutide has over 10 indications in Phase III clinical trials, including chronic kidney disease, MASH, Alzheimer's disease, heart failure with preserved ejection fraction (HFpEF), diabetic nephropathy, and peripheral artery disease.

For generic drugs, while they theoretically could gain market share by offering a price advantage, the continuous iteration and upgrades of original drugs, along with the improvement in managing side effects (as seen with the aforementioned potential star products), as well as potential future price reductions through insurance inclusion or forced price cuts, make it uncertain how much market share generics can capture if the originals reach an excellent balance in efficacy, price, and safety.

MedTrend's observation suggests that issues such as efficacy, production capacity, generics, pricing, and rebound effects upon discontinuation are all testing the innovative potential of GLP-1 players. This situation represents both a challenge and an opportunity. For more details:

• The $5 billion capacity war reignites—what are the challenges and opportunities for peptides?
• Semaglutide Weight Loss Therapy Approved Domestically, Tirzepatide on the Way: Can Domestic Products Replicate the "Peptide Miracle"?
• Semaglutide vs. Tirzepatide: Pharmaceutical Companies and CDMOs Compete for Production Capacity.
• The Most Powerful Anti-Diabetic and Weight-Loss Drug! Eli Lilly's Tirzepatide Enters the Chinese Market

For upstream CDMOs and intermediate raw material suppliers, regardless of how downstream players maneuver, expanding production capacity seems to be the trend, though they should also be cautious of potential future "price wars."