TIRZEPATIDE, a once-weekly dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has emerged as a promising therapy for adults with Type 2 diabetes (T2D) or obesity. Previous trials in the SURPASS programme demonstrated clinically significant reductions in both HbA1c and body weight with tirzepatide. The SURPASS-SWITCH Phase IV study aimed to assess the efficacy and safety of switching to tirzepatide compared with escalating the dose of dulaglutide in adults with inadequately controlled T2D. A key finding of this trial was that switching to tirzepatide led to significantly greater reductions in both HbA1c and weight at 40 weeks.
The multicentre, open-label, randomised trial enrolled 282 adults from 38 sites across five countries. Participants were eligible if they had an HbA1c between 7.0% and 9.5%, a stable body weight, and a BMI of 25 kg/m² or greater. All had been receiving a stable dose of dulaglutide (0.75 mg or 1.5 mg) for at least 6 months, along with up to three oral antihyperglycaemic agents. Participants were randomly assigned either to escalation of dulaglutide to 4.5 mg or maximum tolerated dose (MTD), or to switch to tirzepatide up to 15 mg or MTD. The primary endpoint was change in HbA1c at week 40, with body weight change as the key secondary outcome.
At 40 weeks, mean HbA1c reduction was −1.44% (SE 0.07) in the tirzepatide group and −0.67% (SE 0.08) in the dulaglutide group, with an estimated treatment difference of −0.77% (95% CI: −0.98–−0.56; p<0.001). Weight loss was also significantly greater in the tirzepatide group (−10.5 kg [SE 0.5]) versus the dulaglutide group (−3.6 kg [SE 0.5]), with an estimated treatment difference of −6.9 kg (95% CI: −8.3–−5.5; P < 0.001). Serious adverse events were comparable (7.2% tirzepatide vs 7.0% dulaglutide), with nausea and diarrhoea being the most common side effects.
This study supports the clinical value of switching to tirzepatide in patients with suboptimally controlled T2D on dulaglutide, demonstrating superior glycaemic and weight outcomes. However, the open-label design may introduce bias, and longer-term outcomes remain to be established. These findings may influence treatment strategies in routine diabetes care.
Reference
Billings LK 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. Ann Intern Med. 2025;DOI: 10.7326/ANNALS-24-03849.
