Tirzepatide tied to greater weight loss, glucose control vs. escalated dulaglutide
Key takeaways:
- Participants given tirzepatide lowered their HbA1c by a mean 0.77% more than those given a higher dulaglutide dose.
- More tirzepatide participants hit a weight loss threshold known for disease-modifying effects.
NEW ORLEANS — Patients with type 2 diabetes who switched to tirzepatide rather than escalating their dulaglutide dosage had greater weight loss and improved glucose control, new data showed.
“Time is of the essence in diabetes care,” Liana K. Billings, MD, MMSc, a clinical associate professor at the University of Chicago Pritzker School of Medicine, said during the plenary session at the ACP Internal Medicine Meeting. “We know that 50% of people with type 2 diabetes are not reaching their glycemic goals.”
The findings from the phase 4, randomized, open-label, active-controlled study — simultaneously published in Annals of Internal Medicine — were consistent with previous data on the effectiveness of tirzepatide (Mounjaro/Zepbound, Eli Lilly) for weight reduction.
Trial participants, who possessed an HbA1c anywhere from 7% to 9.5%, a BMI of 25 kg/m2 or greater, and were being treated with 0.75 mg or 1.75 mg dulaglutide (Trulicity, Eli Lilly), were randomly assigned to either tirzepatide (n = 139) or dulaglutide at a higher dose (n = 143).
Medication doses were gradually increased to 15 mg for tirzepatide or 4.5 mg for dulaglutide, or to the highest maximum dose a participant could tolerate.
The study’s primary and secondary endpoints were changes in HbA1c and weight from baseline to 40 weeks, respectively.
The researchers reported that changes in HbA1c during the study period were –1.44% with tirzepatide and –0.67% with dulaglutide (estimated treatment difference = –0.77%; 95% CI, –0.98% to –0.56%).
Overall, 21.3% of those assigned tirzepatide achieved an HbA1c value under 5.7%, compared with 2.4% of those assigned dulaglutide.
Meanwhile, changes in weight from baseline to week 40 were –10.5 kg with tirzepatide and –3.6 kg with dulaglutide (estimated treatment difference = –6.9 kg; 95% CI, –8.3 kg to –5.5 kg).
Billings and colleagues wrote that 58% and 6.8% of patients assigned tirzepatide and dulaglutide achieved weight loss of 10% or greater, respectively, “a threshold that has been observed to have disease-modifying effects.”
Serious adverse events were reported by 7.2% of tirzepatide participants and 7% of dulaglutide participants, while the most common adverse events were nausea and diarrhea.
According to the researchers, there were multiple limitations to the study, including its duration, limited sample size and open-label nature.
They said clinicians need to consider several additional factors when deciding whether to escalate or switch medications, including extra costs and care, tolerability, possible adverse reactions and lowering the risk for cardiovascular events “given that cardiovascular disease is a major cause of death in patients with diabetes.”
Billings concluded that further research is needed to determine whether medication switching “has an impact on longer-term outcomes.”
References:
- Billings LK, et al. Ann Intern Med. 2025;doi:10.7326/ANNALS-24-03849.
- Billings LK, et al. New in Annals of Internal Medicine: Hear it first from the authors. Presented at: ACP Internal Medicine Meeting; April 3-5, 2025; New Orleans.