, 2025-04-21 14:05:00
New data documented dramatic shifts in prescribing for both type 2 diabetes (T2D) and weight loss, particularly with the uptake of tirzepatide (Lilly) and declines in the use of older agents.
Between 2021 and 2023, prescriptions of tirzepatide, semaglutide (Novo Nordisk), and sodium-glucose cotransporter 2 (SGLT2) inhibitors for people with T2D increased dramatically, while the use of metformin, sulfonylureas, and insulin dropped off rapidly, according to an analysis of a large US commercial insurance database. Similarly, among those without diabetes who were prescribed weight-loss medications, the uptake of tirzepatide and semaglutide rose dramatically, while older agents including liraglutide and phentermine declined.
These findings differ from typical trends in medicine, lead author John W. Ostrominski, MD, fellow in cardiovascular medicine and obesity medicine at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, told Medscape Medical News.
“Uptake of novel therapeutics typically is quite delayed. This has been seen in various other conditions, including diabetes, but especially conditions like cardiovascular disease, including heart failure, where implementation of novel therapies that have been shown to have lifesaving benefits can be delayed substantially by multiple years. And even today, there is suboptimal implementation. So such rapid uptake within 18 months of a novel therapy, both for diabetes and ultimately for chronic weight management, I think, was just kind of very staggering to see,” said Ostrominski, who is also a fellow in the Division of Pharmacoepidemiology and Pharmacoeconomics at the Brigham.
Moreover, Ostrominski noted, “There has been substantially increased awareness and appreciation of not only obesity and T2D and the adverse health effects of these two conditions but also a lot of renewed interest because…evolving therapies not only can achieve substantial levels of weight reduction that are increasingly on par with metabolic surgery but also have attendant other wide ranging health benefits, including on blood pressure, major cardiovascular, and kidney risk factors.”
Asked to comment, Rodolfo J. Galindo, MD, director of the Comprehensive Diabetes Center of the University of Miami Health System, and director of Diabetes Management at Jackson Memorial Health System, both in Miami, told Medscape Medical News that the findings match his clinical experience, noting, “I believe it’s related to several factors, including more familiarity with the incretin therapies by the time of tirzepatide approval.”
And, Galindo added, tirzepatide generally has been shown to have higher glucose-lowering potency than semaglutide, although not [yet] via direct comparisons, and to be better tolerated based on his clinical experience. Moreover, “the trends are showing a preferential use for medications that, although are considered expensive or more expensive, have a better profile to treat the underlying pathophysiological defect in T2D, not just ‘hyperglycemia’ as we used to do traditionally. Coincidentally, these drugs are also favoring weight loss.”
Also asked to comment, Joshua J. Neumiller, PharmD, CDCES, president for Health Care and Education of the American Diabetes Association, noted, “Another striking finding was that more than 1 in 5 tirzepatide starts in T2D were in people not taking other background glucose-lowering medications. When combined with the observed decline in metformin use, this likely signals a shift in prescribing of first-line glucose-lowering therapy. As the authors note, this has important implications for cost of diabetes care and health policy in the US.”
The study findings are limited to people who have commercial insurance. And even within the study population, “this research found disparities in uptake/access to newer therapies by race and ethnicity. Unfortunately, previous reports have found that populations with the most to gain from these therapies from a cardiovascular and kidney risk reduction standpoint are often less likely to receive these therapies,” said Neumiller, who is also vice chair of and Allen I. White distinguished professor in the Department of Pharmacotherapy at Washington State University, Spokane, Washington.
‘Staggering’ Uptake of Newer Glucose-Lowering and Weight-Loss Drugs
The study population included 1,830,876 adults with T2D prescribed any glucose-lowering medication between 2021 and 2023, including 1,279,544 who initiated the drugs during that period, and another 92,314 adults without diabetes who were prescribed weight-loss medications.
Following approval of tirzepatide for the treatment of T2D in May 2022, its use reached 12.3% of all glucose-lowering medication prescriptions by December 2023. Of the 90,260 initiating tirzepatide, 21.1% did not have claims for any other glucose-lowering medications.
Any use of SGLT2 inhibitor rose from 14.5% in January 2021 to 24.4% in December 2023, and glucagon-like peptide 1 receptor agonist (GLP-1 RA; mostly semaglutide) from 19.5% in January 2021 to 28.5% in December 2023. Metformin and insulin use remained the most commonly prescribed glucose-lowering medications, but use of both declined during the study period, metformin from 69.2% to 56.2% and insulin from 42.3% to 34.1% (Figure 1).
By December 2023, sulfonylureas and insulin were initiated by less than 10% of incident users, and thiazolidinediones and dipeptidyl peptidase-4 inhibitors by less than 5%.
Tirzepatide uptake among incident users was greater among adults younger than 50 years, women, those of White race, and those with higher body mass indices.
Among incident users with T2D, tirzepatide uptake was more than twice as steep and sustained in the 18 months after US approval and market entry than the 18 months following approval of other GLP-1 RAs.
Among those without diabetes prescribed weight-loss medications, semaglutide 2.0 mg (Ozempic) prescribing rose from 37.8% in 2021 to 45.7% in 2023, while tirzepatide rose from 0% (prior to approval), up to 40.6%. Semaglutide 2.4 mg (Wegovy) rose from 0% prior to its June 2021 US approval to 32.2% by December 2023 (Figure 2).
At the same time, prescriptions for phentermine dropped rapidly from the most used medication in January 2021 (39.6% of all dispensations) to less than 10% by December 2023.
Among the incident users of weight-loss medications, the proportions initiating semaglutide 2.0 mg (Ozempic) rose from 18.6% to 50% in mid-2022 but then declined to 26.6% by December 2023. At the same time, there was a rapid uptake in tirzepatide after October 2022 and semaglutide 2.4 mg (Wegovy) in early 2023.
By the end of 2023, 31.1% of all incidence weight-loss medication dispensations were for tirzepatide, surpassing all others.
‘Richer and More Dynamic’ Picture Anticipated in the Future
This picture will very likely shift again in the near future. Full data will be reported soon from the SURMOUNT-5 trial on comparison of weight loss with tirzepatide vs semaglutide 2.4 mg, for which, top-line results suggest superiority of tirzepatide. This may “further shift these trends in favor of tirzepatide,” Ostrominski said.
Moreover, new data are also expected for newer agents, including the investigational triple agonist retatrutide (Lilly) and the oral nonpeptide GLP-1 RA orforglipron (Lilly).
Ostrominski said, “I think the space is only going to become richer and more dynamic. There are therapies progressing into phase 3 trials and cardiovascular outcomes trials. There are also other therapies in the pipeline that will be targeting additional, more complex hormonal pathways that will have unique health impacts. Will we see increasing use because the additional market entry of other therapies might enhance competition and reduce cost? That’s a hope, of course, and a reason to continue this line of investigation.”
Ostrominski received research support from the National Institutes of Health. Neumiller reported serving on advisory boards for Boehringer Ingelheim/Eli Lilly and Proteomics International. He has also received speaking honoraria for nonpromotional continuing education from Pharmacy Times, Postgraduate Healthcare Education, and Med Learning Group. Galindo received research support from Emory University for investigator-initiated studies from Novo Nordisk, Dexcom, and Eli Lilly and consulting fees from Sanofi, Eli Lilly, Boehringer Ingelheim, Pfizer, and Weight Watchers.
Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape Medical News, with other work appearing in The Washington Post, NPR’s Shots blog, and diaTribe. She is on X @MiriamETucker and BlueSky @miriametucker.bsky.social.
