An intense weight loss arms race is underway as companies push to develop the next paradigm-changing drug.
While the first GLP-1s found early success on the merits of their weight loss effects, the goal now is to optimize efficacy, tolerability and dosing frequency to develop a gentler class of next-generation options. The payoff could be worth billions.
GLP-1 R&D is surging as pharma companies develop a deep pipeline of emerging contenders. But the potential R&D value is largely concentrated among three assets with the highest commercial potential, according to an Evaluate report.
Together, the candidates developed by pharma titans Eli Lilly, Novo Nordisk and Amgen have a combined net present value of about $68 billion and are projected to generate $7.8 billion in global revenue by 2030, according to Evaluate's consensus sales forecasts.
Here's a closer look at the three most valuable GLP-1 R&D projects in Big Pharma’s pipeline.
Eli Lilly's triple receptor agonist retatrutide
Net present value: $28.8 billion
Lilly's next-generation "triple G" candidate retatrutide is the highest-valued GLP-1 R&D asset of the year and could reach nearly $4 billion in global sales by the end of the decade if approved, Evaluate estimates.
Retatrutide's most recent phase 3 readout showed that the injectable treatment helped patients shed more pounds than Novo's Wegovy and Lilly's Zepbound while easing knee pain more than semaglutide.
But many trial participants taking retatrutide discontinued treatment because they were concerned they could be losing too much weight.
The pharma giant said the discontinuation rates were correlated with the starting body mass index of trial participants — most of whom had a BMI above 35 — positioning retatrutide for individuals with severe obesity.
Unlike existing GLP-1 therapies — including Novo's semaglutide, which targets one hormone, and Lilly's tirzepatide, which targets two — retatrutide mimics the activity of three hormones, underpinning its potential as a more efficient weight-loss option.
Lilly is investigating retatrutide in at least seven late-stage trials expected to read out by the end of the year, including a head-to-head obesity study against the best-selling tirzepatide.
Novo Nordisk's amylin + GIP antagonist amycretin
Net present value: $20.9 billion
Novo's next-generation dual-acting obesity candidate, amycretin, ranks second on Evaluate's list, carrying a potential $1.4 billion in global revenue by 2030.
Phase 2 trial data released last November showed that the highest daily oral dose of amycretin triggered a 7.6% placebo-adjusted reduction in weight, while the injectable formulation resulted in an 11.9% reduction in adults with type 2 diabetes after around nine months. By comparison, one mid-stage study of semaglutide, the main ingredient in approved obesity drugs, showed a nearly 14% reduction in weight after one year.
Novo is hedging its bets by developing both oral and injectable versions of amycretin amid fierce market competition from a rapidly expanding pipeline of GLP-1 therapies, including Lilly's highly anticipated obesity pill, orforglipron.
The pharma giant's obesity hopeful could also potentially compete with Lilly's crown jewel tirzepatide and other clinical-stage candidates, including Viking Therapeutics' dual agonist VK2735, and Pfizer's amylin analogue MET-233i.
Amycretin may also offer structural advantages over Novo's other closely-watched obesity asset CagriSema.
Unlike CagriSema, which combines cagrilintide and semaglutide in a dual-chambered pen, amycretin is a single-molecule therapy that can be delivered via a single-chamber device, simplifying manufacturing and reducing production costs.
Both formulations of amycretin are expected to move into late-stage testing in the first half of this year.
Amgen's antibody–peptide conjugate MariTide
Net present value: $18.3 billion
Amgen is targeting a slice of the cardiometabolic and diabetes pie with its once-a-month injectable drug MariTide. The bispecific GLP-1/glucose-dependent insulinotropic polypeptide receptor therapy could ultimately generate nearly $2.5 billion in worldwide sales by the end of the decade.
After pulling the plug on its early-stage obesity candidate AMG786 in May 2024, the company quickly rallied around MariTide, which could have a more favorable tolerability profile than other obesity drugs on the market.
Mid-stage data shows Amgen's monthly MariTide shot was highly effective, leading to an average weight loss of up to 20% after nearly a year. But despite the drug's promising profile, the monthly injection would face stiff competition from entrenched leaders Eli Lilly and Novo Nordisk.
Pfizer is also developing a mid-stage shot it secured in last year's $10 billion Metsera deal, adding to the field of competition.
But MariTide’s potential is expansive.
Amgen has launched six multinational phase 3 studies of MariTide, including one evaluating the therapy in type 2 diabetes. The drug is also being tested for obstructive sleep apnea, and other obesity related conditions like heart failure and cardiovascular disease.
