Tirzepatide led to greater real-world weight loss than semaglutide for adults with obesity
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Key takeaways:
- Adults with overweight or obesity using tirzepatide lost more weight than those using semaglutide.
- Moderate to severe gastrointestinal events were similar between the two medications.
Adults with overweight or obesity lost more weight with the GIP/GLP-1 dual agonist tirzepatide than the GLP-1 receptor agonist semaglutide, according to findings published in JAMA Internal Medicine.
In a head-to-head comparison of the medications using electronic medical records data from Truveta, adults prescribed tirzepatide (Mounjaro/Zepbound, Eli Lilly) were more likely to achieve a 5%, 10% and 15% weight loss than those prescribed semaglutide (Ozempic/Wegovy, Novo Nordisk). There was no difference in moderate to severe gastrointestinal adverse events between the two drugs.
“Because Truveta data provides timely, complete electronic health record data — including prescriptions and medication dispense data — that captures a large and diverse patient population, we’ve been able to compare the head-to-head effectiveness of these two important medications for weight loss in advance of smaller randomized clinical trials,” Patricia J. Rodriguez, PhD, MPH, principal applied scientist at Truveta Research, told Healio. “This study can help to inform patient care and outcomes today, not months from now.”
Rodriguez and colleagues collected EHRs data from a collective of U.S. health care systems. Adults with overweight or obesity who were dispensed tirzepatide or semaglutide for type 2 diabetes treatment from May 2022 to September 2023 had a baseline weight measurement available within 60 days before the first medication dispense and had not used a GLP-1 receptor agonist in the past were included. The primary outcome was on-treatment weight loss for adults receiving each medication. Follow-up continued until treatment discontinuation, switch to a difference medication, last health care encounter or the end of the study on Nov. 3, 2023. Moderate to severe gastrointestinal adverse events, including bowel obstruction, cholecystitis, cholelithiasis, gastroenteritis, gastroparesis and pancreatitis were collected. Researchers used propensity score matching to match 9,193 adults using tirzepatide with 9,192 adults using semaglutide.
“Placebo-controlled trials similarly suggested higher effectiveness of tirzepatide, but study designs differed so results were not directly comparable,” Rodriguez said. “This is the first study to compare the effectiveness of these medications directly in real-world populations with overweight or obesity.”
Greater weight loss with tirzepatide
Of the study group, 54.2% discontinued using their prescribed medication during the study. During a mean on-treatment follow-up of 165 days, adults using tirzepatide lost 5.9% of their body weight at 3 months compared with a 3.6% weight loss with semaglutide. At 6 months, the mean weight loss was 10.1% with tirzepatide and 5.8% with semaglutide. Participants lost a mean 15.3% of their body weight with tirzepatide at 12 months compared with an 8.3% weight loss with semaglutide.
Of participants, 81.8% of adults using tirzepatide lost at least 5% of their body weight compared with 66.5% of those using semaglutide. A 10% or greater weight loss was achieved by 62.1% of the tirzepatide group vs. 37.1% of adults using semaglutide. A weight loss of 15% or higher was achieved by 42.3% of the tirzepatide group vs. 18.1% of the semaglutide group. Adults using tirzepatide were more likely to achieve a 5% weight loss (HR = 1.76; 95% CI, 1.68-1.84), 10% weight loss (HR = 2.54; 95% CI, 2.37-2.73) and 15% weight loss (HR = 3.24; 95% CI, 2.91-3.61) than those using semaglutide.
There was no difference in moderate or severe adverse events observed between the tirzepatide and semaglutide groups.
“As a practicing cardiologist and researcher, having the most timely data to inform patient care is paramount. Assessing the real-world effect of semaglutide and tirzepatide on weight loss provides a glimpse into what we may see with the recently approved obesity drug tirzepatide and how it might compare with semaglutide,” Tyler J. Gluckman, MD, MHA, FACC, FAHA, FASPC, a cardiologist at Providence Health and medical director at the Center for Cardiovascular Analytics, Research, and Data Science at Providence Heart Institute, told Healio. “Because tirzepatide was only approved by the FDA in mid-2022 for type 2 diabetes, the ability to rigorously analyze its use (on- and off-label) for a broad population of patients with overweight or obesity, not just a subset captured in insurance databases, has the power to greatly improve our understanding of how these agents are being used in everyday practice and the effect that they’re having.”
Consider individual factors when prescribing
Tirzepatide was tied to greater weight loss than semaglutide, but providers should consider each person with obesity’s circumstances when considering which medication to prescribe, according to Nicholas L. Stucky, MD, PhD, vice president of Truveta Research and practicing infectious disease physician at Providence Portland Medical Center.
“Patients on both medications experienced substantial weight loss, and we observed no difference in the risk of gastrointestinal adverse events,” Stucky told Healio. “In addition to effectiveness, factors like medication availability and insurance coverage will likely play a role in deciding which medication to initiate. So, providers should evaluate these findings — alongside those other considerations — as they assess which option might be best for their individual patients.”
Rodriguez said their research group plans to examine more trends with semaglutide, tirzepatide and other medications in the future, including outcomes for treating other conditions, barriers to equitable access, health outcomes following medication discontinuation and trends for restarting a medication.
For more information:
Nicholas L. Stucky, MD, PhD, can be reached at nicholass@truveta.com.
Perspective
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Katherine H. Saunders, MD, DABOM
There is much to learn from this publication, but it is important to acknowledge the study’s limitations before jumping to conclusions. The retrospective, observational analysis of electronic health record data examined tirzepatide vs. semaglutide in a heterogeneous population prescribed medication at a variety of doses for a variety of indications. Half the patients had a diagnosis of type 2 diabetes, so their prescriptions were likely for diabetes treatment, obesity treatment or both. The other half did not have a diagnosis of type 2 diabetes, so many of them likely received prescriptions off-label for several diagnoses including overweight, obesity, prediabetes, polycystic ovarian syndrome, drug-induced weight gain, etc. Most importantly, many participants did not receive the FDA-approved dosages for obesity.
In the words of my brilliant colleague, Ted Kyle, RPh, MBA, “Sweeping generalizations about one or the other drug being better [for obesity] therefore can be misleading. Different people have different needs and will have different experiences.”
So, what can patients and clinicians learn from this study? The high dropout rate is striking, but not surprising unfortunately. There are so many barriers to continuation of GLP-1 therapy. In addition to the obvious barriers of coverage, cost, shortages and adverse events, we see tons of patients who have experienced improper dose titration and who have received insufficient education and support.
I cannot speculate about the prescribing protocols in this particular study, but in general, we hear reports from patients daily about a GLP-1 medication being prescribed at the end of a jam-packed medical encounter with very limited guidance and zero discussion of alternative medication options. So many clinicians these days equate obesity treatment with a GLP-1 prescription, and they do not have the training to deliver evidence-based, long-term obesity care.
In an ideal world, medication discontinuation would be rare because clinicians would be trained in obesity medicine and have the time and resources to deliver personalized care. Treatment would be delivered with plenty of education and support as well as prescriptions selected from the entire armamentarium of medications, many of which are not associated with limited coverage, high cost and rampant shortages. Dose titration would be individualized based on effectiveness and tolerability, and protocols would identify side effects early and certainly way before adverse events occurred or patients stopped treatment on their own.
Both patients and clinicians require a significant obesity treatment infrastructure to manage the complex, progressive, chronic disease. Patients should expect nothing less. And until the number of obesity experts increases exponentially, more clinicians who prescribe GLP-1 medications for obesity should consider even a few hours of continuing medical education on comprehensive, evidence-based care.
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