Groundbreaking Drug Launches
Semaglutide/Cagrilintide (CagriSema)
Mechanism of Action: Amylin receptor agonists; Glucagon-like peptide-1 receptor agonists Drug class: Glucagon-like peptides Originator: Novo Nordisk Indication: Obesity
Expected approval: Late 2026
Trials: REDEFINE program (REDEFINE 1 and REDEFINE 2), NCT06780449
Obesity
Obesity is a complex condition characterized by excess body fat. It is not merely a cosmetic issue but a serious medical problem that raises the risk of various other diseases and health complications. These include heart disease, diabetes, high blood pressure, high cholesterol, liver disease, sleep apnea, and certain types of cancer.
Symptoms
Body mass index (BMI) is commonly used to assess obesity. To calculate BMI, multiply weight in pounds by 703, then divide by height in inches squared. Alternatively, divide weight in kilograms by height in meters squared. There are also several online calculators available to help determine BMI.
Why is Semaglutide/Cagrilintide poised to make an impact in 2026?
Semaglutide/Cagrilintide (CagriSema) is expected to be a major industry inflection point in 2026, as it represents Novo Nordisk’s investigational next-generation weight-loss therapy that is approaching a pivotal FDA regulatory milestone. Several factors underpin its anticipated impact:
Regulatory Milestone: Novo Nordisk submitted a New Drug Application (NDA) to the U.S. FDA in late 2025, with a regulatory review and potential approval decision anticipated in 2026.
First-in-Class Innovation: If approved, CagriSema would become the first injectable therapy combining a GLP-1 receptor agonist with an amylin analogue, introducing a novel dual-mechanism approach to weight management.
Addressing a Critical Unmet Need: With obesity recognized as a chronic and complex disease, there remains a strong demand for more effective long-term therapies. CagriSema is expected to expand the treatment landscape by offering patients and clinicians a highly effective new management option.
Compelling Clinical Efficacy: Clinical trial data demonstrate substantial weight-loss outcomes, with participants without type 2 diabetes achieving nearly 23% average body-weight reduction and those with type 2 diabetes around 16%—outperforming semaglutide monotherapy and signaling a meaningful advance in obesity treatment.
Market Disruption Potential: Positioned as a potential successor to Novo Nordisk’s blockbuster Wegovy, CagriSema is a cornerstone of the company’s strategy to maintain leadership amid intensifying competition from agents such as Eli Lilly’s Zepbound (tirzepatide).
“CagriSema’s peak annual sales were initially projected at up to $20B, but have since been revised to approximately $7.25B following recent trial comparisons with competing therapies”
Novo Nordisk reported that its combination therapy, CagriSema, helped patients lose up to 23% of their body weight after 68 weeks—about 20 percentage points more than those on placebo and 7 percentage points more than those using the company's popular weight-loss drug, Wegovy. However, this result missed Novo's target of 25% weight loss, which had been the company’s goal for the trial. Investors were expecting up to 27% weight loss, according to a survey by Jefferies analyst Peter Welford.
Additionally, about 57% of cagrisema-treated patients reached the highest dose by the end of the trial, compared to 70% for those on Wegovy and 83% for those on cagrilintide, one of cagrisema’s components. This raised concerns about CagriSema's tolerability.
Novo had hoped CagriSema could outpace its primary weight-loss competitor, Eli Lilly, whose drug Zepbound helped patients lose up to 21% of their body weight. Unlike Zepbound, which uses a single drug targeting two gut hormones, CagriSema involves two separate injections, potentially limiting its commercial appeal given the challenges drug companies face in meeting demand for weight-loss treatments.
The trial results are a setback for Novo's ambitions in the obesity market, disappointing analysts and investors who hoped for continued dominance in a sector projected to reach over $100 billion in annual sales. Novo faces competition from Lilly and other biotechnology firms aiming for a piece of the market.
In December 2024, Novo's stock dropped 20%, while Lilly's rose 6%. In response, Novo plans a new trial for its CagriSema drug in 2025, aiming for better results. In March 2025, Novo shares fell 6.3% after disappointing results from the REDEFINE 2 trial of CagriSema, which helped obese type 2 diabetes patients lose 13.7% of their weight over 68 weeks. Investors had hoped for better results, expecting a 15% or higher weight loss. Despite the setback, Novo plans to share the results with regulators and file for CagriSema's approval in the first quarter of 2026.
Regulatory milestones for Semaglutide/Cagrilintide
Setbacks from the REDEFINE program
The REDEFINE program marked a setback for Novo Nordisk's ambitions in the obesity market. Despite the company's strong track record in diabetes care, the program's results were disappointing, delaying the expected advancements in its portfolio of obesity treatments. This setback has challenged Novo Nordisk's plans to expand its influence in the rapidly growing weight management sector, highlighting the complexities and uncertainties of developing effective therapies for obesity. Nonetheless, the company remains committed to advancing its research and addressing the unmet needs of obese individuals.
REDEFINE 1:
A phase 3 study conducted by Novo Nordisk, evaluated the efficacy and safety of CagriSema—a fixed-dose combination of cagrilintide and semaglutide—administered subcutaneously once weekly over 68 weeks (NCT05567796).
REDEFINE 2:
A phase 3 clinical study designed to evaluate the efficacy and safety of CagriSema—a combination of cagrilintide and semaglutide—administered subcutaneously once weekly in adults with type 2 diabetes and obesity or overweight (NCT05394519).
“REDEFINE 1 results led to a $125 billion drop in Novo Nordisk's market value, while REDEFINE 2 caused a 6.3% stock decline”
Launched a New Trial of Its Next-Generation CagriSema
Novo Nordisk has launched a new Phase 3 trial for its next-generation obesity drug, CagriSema, which will evaluate various doses and extended treatment durations.
NCT06780449:
A phase 3, randomized, double-blind clinical trial aims to evaluate the efficacy and safety of CagriSema, a combination of cagrilintide and semaglutide, administered once weekly, compared to a placebo in obese adults.
