Both semaglutide and tirzepatide would need big price cuts to be seen as a good buy for the US healthcare system.
Two popular medications used in the fight against obesity—semaglutide (Wegovy; Novo Nordisk) and tirzepatide (Zepbound; Eli Lilly)—are priced too high to be considered cost-effective by currently acceptable standards, new research shows.
The price of tirzepatide in the United States would need to be cut by more than 30% and semaglutide’s price slashed by 82% to achieve the frequently cited cost-effectiveness threshold of $100,000 per quality-adjusted life-year (QALY) gained, say investigators.
The new agents, when compared with older generations of weight-loss medications, offer “amazing” long-term health benefits, but the price of the drugs is a problem when it comes down to willingness to pay, lead investigator Jennifer H. Hwang, DO (University of Chicago, IL), told TCTMD.
“The cost [of the medications] is the primary factor for cost-effectiveness,” she said. “If you look at the long-term health impact and see how many diabetes and obesity cases are averted, they’re still somewhat expensive [within] a generally accepted effectiveness threshold in the United States. They are still not cost-effective at their current net prices that we used.”
Daniel C. Malone, PhD (University of Utah, Salt Lake City), who has also investigated the cost-effectiveness of anti-obesity medications, said the new agents “are expensive, no question,” and that their benefits need a long period of time to accrue.
“You have an upfront investment of several thousand dollars and the benefits don’t occur for many years,” he told TCTMD. “For most of these agents, therefore, by the time you discount those future events back in terms of quality-adjusted life-years, and also in terms of the economic value of those costs, it’s challenging for new products to be cost-effective. This doesn’t apply just to these agents, but quite frankly almost all drugs that are coming to the market. If they have long-term consequences, they just can’t overcome the high price.”
They are still not cost-effective at their current net prices that we used. Jennifer Hwang
Competition between drug manufacturers will lead to lower prices, something that has already started to happen, said Malone. Eli Lilly recently reduced the price of various tirzepatide doses for people who buy directly from the company, a move that was matched by Novo Nordisk. Other drugs are also in development, including oral glucagon-like peptide 1 (GLP-1) receptor agonists, which might be favored by patients and could lead to further price cuts for injectables.
“The sand is shifting underneath the feet of people like myself and others that do these analyses,” said Malone. “These products tend to have downward pressure on price over time, and we’re obviously seeing that.”
Lifetime Benefits vs Cost
Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, was approved for weight management in 2023, while semaglutide, a GLP-1 receptor agonist, was approved 2 years earlier. Although weight loss may be greater with tirzepatide, semaglutide has an indication for CV event reduction based on the SELECT trial, where the drug reduced the risk of MACE by 20% compared with standard care in patients with overweight/obesity and preexisting CVD. Tirzepatide is currently being investigated in the SURMOUNT cardiovascular outcomes trial of adults with obesity.
The new study, which was published last week in JAMA Health Forum, evaluated the lifetime health benefits and cost-effectiveness of four antiobesity medications combined with lifestyle modification versus lifestyle changes alone. In addition to semaglutide and tirzepatide, the researchers evaluated two older anti-obesity medications: phentermine-topiramate (Qsymia; Vivus) and naltrexone-bupropion (Contrave; Currax), which were approved in 2012 and 2014, respectively.
The analysis was based on 4,823 individuals (mean age 48 years; 51% female), a sample representing 126 million US adults, in the National Health and Nutrition Examination Survey (NHANES) 2017-2020 database who met clinical inclusion criteria for obesity or overweight plus at least one weight-related comorbidity such as diabetes, hypertension, dyslipidemia, or cardiovascular disease.
The model allowed researchers to run individual-level simulations where people received one of the four medications in addition to lifestyle changes or adhered to lifestyle modifications alone. The model accounted for changes in weight and cardiovascular risk factors after 2 years of treatment, drug discontinuation due to adverse events, and long-term cardiovascular disease events, such as coronary heart disease and stroke.
The sand is shifting underneath the feet of people like myself and others that do these analyses. Daniel Malone
Drug prices were estimated using SSR Health and reflected rebates and discounts across Medicaid, Medicare, and commercial insurers. The mean yearly net prices used for the analysis were $8,412 for semaglutide, $6,236 for tirzepatide, $1,786 for phentermine-topiramate, and $420 for naltrexone-bupropion. Lifestyle modification was estimated to cost $1,692 annually.
Over a lifespan, tirzepatide and semaglutide would avert 45,609 and 32,087 cases of obesity per 100,000 people, avoid 20,854 and 19,211 incident cases of diabetes per 100,000 individuals, and prevent 10,655 and 8,263 cardiovascular disease events per 100,000 people, respectively.
Compared with lifestyle alone, the incremental QALYs gained were 0.06 with naltrexone-bupropion, 0.14 with phentermine-topiramate, 0.25 with semaglutide, and 0.35 with tirzepatide. The incremental cost-effectiveness ratio (ICER), which factors in cost per QALY, was $85,229 with phentermine-topiramate, $467,676 with semaglutide, and $197,023 with tirzepatide. Naltrexone-bupropion was deemed cost-saving with an ICER of $33,005/QALY when used in patients with obesity.
In a threshold analysis, the researchers say tirzepatide would need to be cut down to $4,334 annually to achieve cost-effectiveness at $100,000/QALY. Semaglutide would need to be lowered to $1,522 from its estimated net price to be considered cost-effective.
Other Benefits of Weight-Loss Drugs
To TCTMD, Hwang noted that recent studies have shown that semaglutide and tirzepatide also positively impact the risk of obstructive sleep apnea, pain related to osteoarthritis, and nonalcoholic fatty liver disease. These benefits, which weren’t factored into the microsimulation model, would improve the anticipated cost-effectiveness of treatment.
“The flip side [is that] we simulated the maximum benefit, meaning we had everybody experience the maximum weight loss and also cardiovascular [benefit], and had that sustained for a lifetime,” said Hwang. “I know some might argue that there are additional health benefits, but I don’t think it would really change our numbers drastically.”
Hwang also believes the drugs will come down in price over time with increased market competition.
Malone noted that when atorvastatin first came to market for LDL cholesterol lowering, it was priced around $5 per tablet but it and other statins are now available for pennies a day. While semaglutide and tirzepatide are early in their patent life, they won’t always be expensive drugs.
“Comparatively speaking,” said Malone, “they’re going to be good buys for society.”