The pipeline for anti-obesity medications has exploded over the past few years. While Novo Nordisk and Lilly are the leaders in the GLP-1/incretin space, there is plenty of room for competition and innovation in the field. Below are three themes that will define the future of weight loss management:

The obesity market is still relatively untapped. It is a market that can not only support but may actually benefit from a variety of competing products

• The obesity market is likely to increase from $2.4 billion currently to over $77 billion. Currently, less than 5% of people with obesity are using a GLP-1 or other prescription pharmaceutical.
• The biggest hurdle to explosive growth of the market is insurance coverage. That will depend on 1) continued data showing the health benefits of weight loss from these products and 2) competitive pressure from multiple products bringing the price down to a level which can be sustained by both government and commercial insurance.
• Data from the SELECT trial showing Wegovy’s ability to reduce risk of major cardiovascular events (MACE) by 20% is an important step in the right direction, and it will be interesting to see how quickly this pushes insurance coverage in the U.S. market.
• Companies developing new therapies, whether novel or not, should focus on the expansion of the obesity market and less on competing with existing products. Smaller companies may be attractive targets to large pharmas who want to buy their way in to the space.

Competing on weight loss alone is not going to propel a product to best-in-class status. Product differentiation on a number of aspects like speed of weight loss, convenience, and cost will be increasingly valuable as the field becomes more crowded

• Lilly’s retatrutide, which showed a mean 24.2% body weight reduction in a mid-stage trial, is likely the ceiling for safe weight loss, rivaling bariatric surgery. Lilly’s tirzepatide and Novo Nordisk’s CagriSema will also launch in the next year or two with >20% weight loss potential.
• New mechanisms of action may not differentiate in terms of weight loss but have the opportunity for favorable drug profiles in other ways, like weight loss speed, fat versus lean mass reduction, and targeted fat reduction. Individuals will also respond differently to different approaches, and people seeking weight loss are used to trying multiple strategies.
• New combinations of GLP-1 family members with each other and with other targets are advancing through the pipeline. Examples include survodutide, Boehringer Ingelheim and Zealand Pharma’s dual glucagon/GLP-1 agonist, which is about to reach phase 3 trials. Amgen’s GLP-1 agonist/GIPR antagonist AMG133 is currently in phase 2.
• Oral alternatives to the subcutaneous injectibles will be extremely well received if efficacious. Novo Nordisk, Lilly, and Pfizer all have entries in this category. • Products with completely new mechanisms outside of incretins may be the most coveted of all. Both Lilly and Novo Nordisk recently spent >$1 billion acquiring an obesity-targeting antibody and a cannabinoid receptor blocker, respectively.

Safety and the chronic nature of treatment are still major roadblocks for significant uptake of obesity medicines

• The incidence and severity of GI adverse events is notorious across the GLP-1 class, and companies so far do not have a product which avoids these side effects. As new investigations of thyroid cancer risk and suicidal ideation work their way through Europe, any product which can claim a milder safety profile will have a significant advantage.
• New data from the SURMOUNT-4 trial of tirzepatide underscores what is already known anecdotally: going off drug treatment leads to a huge weight regain. Any future therapy or treatment strategy which can increase the durability of weight loss will likely upend the market completely.