The nausea and other gastrointestinal side effects of weight loss drugs like Novo Nordisk’s Wegovy or Eli Lilly’s Zepbound will limit how much these drugs can help patients and stunt the overall obesity market unless we approach the problem head on.
GLP-1s are the most transformative and wildly successful class of new drugs in the last quarter century, with millions of patients with diabetes and obesity having already benefitted from their dramatic effects.
In the first half of 2025, revenues for just two GLP-1 drugs, Wegovy and Zepbound, hit $10.5 billion—with sales of the latter overtaking blockbuster Keytruda for the first time—and the global market is projected to reach at least $95 billion by 2030.
Yet lurking beneath these shiny blockbuster numbers and their cultural omnipresence is a major problem that, at best, receives little attention and, at worst, is being ignored: severe nausea and vomiting lead many patients to discontinue treatment.
Although clinical trial reports and drug labels classify these side effects as “mild to moderate,” patients experiencing GLP-1-associated nausea on a daily basis would clearly beg to differ—and they have no approved therapeutic options to help them. As a result, millions fail to achieve the full benefits GLP-1s can offer, and billions in potential revenue are left on the table.
Big Pharma’s inertia on solving this problem highlights a paradox of drug development: industry appears to take treatment-associated side effects more seriously in acute diseases than in chronic ones.
Cancer is the perfect example of such an acute disease. Decades ago, industry recognized that chemotherapy-induced nausea made it difficult for cancer patients to tolerate treatment and developed drugs to treat patients’ nausea and keep them on chemotherapy. But the problem of GLP-1-associated nausea, in diseases that are potentially as life-threatening as cancer in the long term, has not been met with the same urgency.
At Neurogastrx, we see this as a disservice to patients who could benefit from these drugs, and we are working hard to develop treatments that can help GLP-1 users continue taking their medication. Unfortunately, we seem to be venturing into new territory, without throngs of other biotechs or the Big Pharma GLP-1 makers themselves doing the same.
The sheer size of the GLP-1 market seems to have obscured the industry’s perception of the true scale of the problem and downplayed the need for innovative therapies that could address it. Unless something is done, patients are the ones who will continue to suffer most.
Discontinuation Is Disadvantageous
Agonists of glucagon-like peptide-1 (GLP-1) receptor were first approved to treat type 2 diabetes (T2D) but are becoming increasingly popular as weight loss drugs, where they can help patients lose an average of 15–25% of body weight after one year. Because excess weight is linked to T2D, dyslipidemia and cardiovascular disease, GLP-1s can also improve the overall health of patients as they lose the weight.
The global market for GLP-1s is huge: Goldman Sachs projects the obesity market alone will grow to $95 billion by 2030. More startling is that the bank previously projected a $130 billion market by 2030, but revised its estimate downward due to multiple factors, including patient discontinuations. Therein lies the problem. Up to 70% of patients on GLP-1s experience gastrointestinal side effects, including nausea. According to a JAMA Network Open article, nearly half of patients with T2D and nearly two-thirds without diabetes discontinue GLP-1s within a year, with GI side effects cited as the predominant reason for withdrawal. Expansion of GLP-1s to other disease areas, from Alzheimer’s disease to sleep apnea, means the problem will grow exponentially.
These numbers bely the clinical trial results, investigator reports and GLP-1 drug labels that classify nausea and vomiting as “mild-to-moderate.” A person who feels “mildly” nauseated still cannot function normally. Additionally, classifying someone’s experience as “mild” in a clinical trial is not a measure of the patient’s experience, which in some cases can be much more severe. This leads many patients to trade the weight-loss benefits of GLP-1s for not feeling sick. When they do, they also lose out on the full benefits of these drugs; patient who discontinue GLP-1s regain on average two-thirds of their lost weight within one year.
Tolerability for Acute Vs. Chronic Disease
With about 16 million patients in the U.S. taking GLP-1s, the nausea and vomiting they induce is as pressing a societal need as the diseases GLP-1s treat. The problem is also arguably equal in scale to cancer, but there, approved treatments for chemotherapy-induced nausea have been available for decades.
As of 2022, about 18 million people in the U.S. were living with cancer, with about 2 million new cases diagnosed each year. Chemotherapies, the mainstays of cancer treatment, have nausea and vomiting among their side effects. Because cancer is an acute, life-threatening condition, patients have a high tolerance for the side effects of therapies that put their disease in remission and improve their survival.
Even so, drugs like Zofran (ondansetron) are available to reduce chemotherapy-induced nausea, thus helping patients stay the full course of their chemotherapy and achieve the best possible outcomes. However, this same logic—treating the side effects to keep patients on their therapy and improve outcomes—has not extended to a chronic, life-threatening condition like obesity and the nausea associated with GLP-1 therapies.
Granted, obesity is not life-threatening in precisely the same way as cancer. Patients with untreated obesity are not usually in imminent danger of having a cardiovascular event. Still, their risk of an event at some point in the future is high. When examined from this perspective, any rationale for addressing treatment-associated nausea differently in obesity than in cancer vanishes. Both deserve the same level of urgency.
Innovation Is the Answer
Pharma is unlikely to innovate its way around the problem with novel GLP-1 analogs or differing routes of administration because mounting evidence suggests nausea is an on-target effect of the drugs. Orthogonal solutions—drugs that hit different targets to control nausea—are therefore needed.
The problem of GLP-1-associated nausea can be tackled on multiple fronts. Physicians need to recognize the problem is more than a mild, clinical inconvenience to their patients. Patients should advocate loudly for therapies to reduce their nausea so they can continue losing weight and getting healthier. Above all, biopharma companies must be willing to invest in innovative therapies with novel mechanisms of action.
Neurogastrx is doing its part to solve the problem by developing NG101, a clinical-stage investigational treatment for GLP-1-associated nausea that could help patients with obesity stay on therapy. We hope that more companies and investors will recognize why treatment-induced nausea in obesity deserves the same attention it already has in cancer—and how that recognition could benefit GLP-1 patients and manufacturers alike.
