Switching to Tirzepatide Shows Greater Benefit Than Escalating Dulaglutide in T2D, Obesity

Patients with inadequately controlled type 2 diabetes and obesity experienced greater HbA1c reduction and weight loss after switching treatment to tirzepatide rather than escalating current dulaglutide doses.1

These findings, from the phase 4 SURPASS-SWITCH trial (NCT05564039), were presented at the American College of Physicians (ACP) Internal Medicine (IM) Meeting 2025, held April 3-5, in New Orleans, Louisiana, by Liana K. Billings, MD, Department of Medicine, Endeavor Health/NorthShore, Skokie, and Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, Illinois.

Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, is FDA-approved for the treatment of adults with type 2 diabetes or obesity.2,3 The therapy previously demonstrated clinically meaningful reductions in hemoglobin A1c (HbA1c) and body weight in the SURPASS phase 3 clinical trial. These new findings are from the SURPASS-SWITCH phase 4, randomized clinical trial (RCT), conducted in 38 sites across 5 countries.

The study enrolled 282 adults with HbA1c 7.0% or greater to 9.5% or less with stable body weight and body mass index of 25 kg/m2 or greater, that were receiving a stable dose of dulaglutide (0.75 or 1.5 mg) for at least 6 months and 0 to 3 oral antihyperglycemic medications for at least 3 months.1

Participants were randomized to switch to tirzepatide 15 mg or maximum tolerated dose (MTD; n = 139) or to escalate dulaglutide to 4.5 mg or MTD (n = 143). The study’s primary end point was change from baseline in HbA1c at week 40. The key secondary end point was change from baseline in weight at week 40.1

The investigators found that the change from baseline in HbA1c at week 40 was −1.44% (standard error [SE], 0.07) with tirzepatide and −0.67% (SE, 0.08) with dulaglutide (estimated treatment difference, −0.77% [95% CI, −0.98% to −0.56%]; P < .001). The change from baseline in weight at week 40 was −10.5 kg (SE, 0.5) with tirzepatide and −3.6 kg (SE, 0.5) with dulaglutide (estimated treatment difference, −6.9 kg [95% CI, −8.3 to −5.5 kg]; P <.001). There were similar rates of serious adverse events (AEs) across both the tirzepatide (n = 10; 7.2%) and dulaglutide (n = 10; 7.0%) groups. The most common treatment-emergent AEs were nausea and diarrhea.1

“These drugs are game changers in a lot of ways, but like any game changer, it's a balance of benefits and harms,” Christine Laine, MD, MPH, Professor of Medicine in the Division of Internal Medicine of the Sidney Kimmel Medical College at Thomas Jefferson University and Editor-in-Chief, Annals of Internal Medicine and Senior Vice President, ACP, told HCPLive while onsite. “What do you do when you prescribe one of these medications and people are not having either the meeting targets for weight loss or targets for glycine and control? …When is it time to switch therapy? And what do we know about different strategies for switching?” Laine served as moderator for the Friday plenary session, “Hear it First From the Authors”, that Billings presented the trial findings at.

REFERENCES

1. Billings LK, Winne L, Sharma P, et al. Comparison of Dose Escalation Versus Switching to Tirzepatide Among People With Type 2 Diabetes Inadequately Controlled on Lower Doses of Dulaglutide: A Randomized Clinical Trial. Presented at: ACP IM Meeting 2025; April 3-5; New Orleans, Louisiana.

2. Campbell P. Tirzepatide (Mounjaro) Wins FDA Approval for Type 2 Diabetes. News article. HCPLive. May 13, 2022. https://www.hcplive.com/view/tirzepatide-wins-fda-approval-for-type-2-diabetes

3. Campbell P. FDA Approves Tirzepatide (Zepbound) for Chronic Weight Management. News article. November 8, 2023. https://www.hcplive.com/view/fda-approves-tirzepatide-zepbound-chronic-weight-management