ATLANTA — People without type 2 diabetes (T2D) who have already lost weight using various methods, including a different GLP-1, can still achieve further weight loss by starting tirzepatide, new real-world data from a retrospective cohort study suggested.

“Clinically meaningful weight loss is still possible in patients who are weight-reduced,” said study author Sarah R. Barenbaum, MD, obesity medicine director, Gastrointestinal Metabolic and Bariatric Surgery, Weill Cornell Medicine, New York City, who presented the findings at Obesity Week 2025.

“But a patient who is weight reduced may experience more modest results than a patient starting at their highest weight,” she told Medscape Medical News.

Indeed, the more weight the person had already lost from their maximum before starting tirzepatide, the less weight they lost with the dual incretin receptor agonist. And when patients were divided by T2D status, the findings were significant only in those without T2D.

“These findings were not surprising based on clinical experience but are important because other studies have not looked at this in real-world practice yet,” said Barenbaum. “Clinical practice is different from the clinical trials, and we need more real-world predictors to help better guide treatment strategies and shared decision-making with patients.”

Continued Weight Loss

The study included 293 patients who had been prescribed tirzepatide between May 15, 2022, and January 15, 2023, and who stayed on it for at least 6 months. Of those, 133 had already lost at least 10% of their total body weight prior to starting tirzepatide, while the other 160 had lost none or less than 10%.

At baseline, the weight-reduced patients were older (55.6 vs 49.8 years, P < .001), but the sex distribution was the same (65% women in both groups); about 60% of both groups were White individuals. T2D was more common in the weight-reduced group (50% vs 21%, P < .001). As would be expected, baseline BMI was lower in the weight-reduced group (34.90 vs 37.19, P = .007), as was body weight (235.51 vs 214.61 lb, P < .001).

The previously weight-reduced group tended to start tirzepatide at a higher dose. By 6 months, both groups had increased their doses substantially, and though the dose in the weight-reduced patients remained slightly higher, on average, the overall change in dose from baseline to 6 months did not differ significantly, Barenbaum reported.

At 6 months with tirzepatide, the weight-reduced group lost an additional 7.24%, compared with 10.30% in the non-weight-reduced group (P < .001). The proportions losing at least 5% of their body weight were 55% vs 80% (P < .001), at least 10% of their weight were 29% vs 47% (P = .001), and at least 15% were 13% vs 22% (P = .043).

“Linear regression showed a significant positive association between the percent of weight that patients had lost before starting trazepatide and subsequent percent weight change from baseline to 6 months,” she said.

Among the 193 patients with T2D, the mean percent weight loss didn’t differ between those who were weight reduced and those who weren’t (5.5% vs 5.7%, P = .8), whereas the difference was significant among those without T2D (9% vs 11%, P = .013).

“Treatment must be individualized, and counseling should reflect realistic goals and expectations. And as with everything that we do, shared decision-making is crucial, and these data points can help us along those conversations with patients and help manage expectations,” Barenbaum concluded.

Switching From Semaglutide to Tirzepatide

In a separate poster, Barenbaum’s team reported that of the initial cohort of 293 patients, 54% (n = 157) had switched to tirzepatide from semaglutide, of whom 44.6% (n = 70) were on a therapeutic dose. Among 61 patients who had switched from a therapeutic dose of semaglutide to tirzepatide due to weight-loss plateau (n = 28) or nonresponse (n = 33), the mean additional weight loss on tirzepatide at 6 months was 5.3%.

Those who had switched due to weight-loss plateau lost an additional 8.1%, while those who had switched due to nonresponse lost 2.9% with tirzepatide (P < .001).

“These findings highlight the importance of understanding the rationale for switching treatments when setting expectations and individualizing obesity management plans. These findings also underscore the need for additional obesity therapies that act through non-GLP-1 pathways, given that not all patients respond to these medications,” the authors concluded.

The Importance of Real-World Data

Asked to comment, session moderator Kimberly A. Gudzune, MD, chief medical officer of the American Board of Obesity Medicine, told Medscape Medical News, “There are so many questions on the front lines of the art of medicine that we don’t have clinical trials to answer. I think this type of retrospective real-world data are really important to begin to get a sense of what can we expect.”

“When we’re trying to counsel patients, we don’t want to say, oh, you’re going to lose 15% [of body weight] because that’s what the clinical trials say,” she said. If they’ve already lost weight that’s not what they’re going to see.

Much depends on the patient’s health goals, Gudzune added. “There are some folks who reach a plateau, and they still have health goals that they want to achieve, whether it’s improvement in their blood sugar or blood pressure, or they want to regain more mobility.”

“So what do we do in that situation? I think this is the sort of question this study is also trying to address,” she said.

Barenbaum and Gudzune reported having no disclosures. 

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.