medwireNews: Switching to tirzepatide leads to greater reductions in glycated hemoglobin (HbA1c) and greater weight loss than escalating dulaglutide dose in people with type 2 diabetes on submaximal doses of dulaglutide, show results of the phase 4 SURPASS-SWITCH study.
Previous data from the SURPASS phase 3 clinical trials indicated that tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide (GLP)-1 receptor agonist, showed clinically meaningful reductions in HbA1c and bodyweight in people with type 2 diabetes.
However, the effectiveness of switching from a GLP-1 receptor agonist like dulaglutide to tirzepatide was unclear because the studies excluded people who had taken GLP-1 receptor agonists in the 3 months prior to recruitment.
To address this, SURPASS-SWITCH included 282 adults with inadequately controlled type 2 diabetes (HbA1c 7.0–9.5%; 53–80 mmol/mol), stable bodyweight, and a BMI of 25 kg/m2 or greater, who had received a stable dose of dulaglutide (0.75 or 1.5 mg) for at least 6 months and up to three oral antihyperglycemic medications for at least 3 months.
The participants, from 38 sites across five countries in North America and Europe, had a mean diabetes duration of 11.2 years, a mean HbA1c of 7.82% (62 mmol/mol), and a mean weight of 96.9 kg at baseline.
They were randomly assigned to discontinue dulaglutide and switch to once-weekly subcutaneous tirzepatide 2.5 mg, escalating to 15.0 mg or maximum tolerated dose (MTD; n=139), or to continue with and escalate once-weekly subcutaneous dulaglutide to 4.5 mg or MTD (n=143).
Anita Kwan (Lilly Corporate Center, Indianapolis, Indiana, USA) and co-authors report in the Annals of Internal Medicine that, after 40 weeks of treatment, people who switched to tirzepatide had a significantly greater reduction in HbA1c than those who continued dulaglutide.
Specifically, the mean reduction in HbA1c from baseline to week 40 was 1.44 percentage points with tirzepatide and 0.67 percentage points with dulaglutide. At week 40, mean HbA1c was 6.38% (46 mmol/mol) and 7.15% (55 mmol/mol), respectively.
In addition, more patients given tirzepatide versus dulaglutide achieved HbA1c targets of less than 7.0% (53 mmol/mol; 84.4 vs 46.5%), less than 6.5% (48 mmol/mol; 73.0 vs 22.0%), and less than 5.7% (39 mmol/mol; 21.3 vs 2.4%).
The researchers also looked at the change in weight from baseline to week 40 and observed significantly greater weight loss with tirzepatide than with dulaglutide, at 10.5 kg and 3.6 kg, respectively.
The proportion of patients who lost at least 5% of their body weight was 82.4% in the tirzepatide arm and 37.6% in the dulaglutide arm. For a weight loss target of at least 10%, the corresponding proportions were 58.0% and 6.8%, while 29.0% of participants given tirzepatide and 0.8% of those given dulaglutide achieved weight loss of 15% or greater.
The serious adverse event (AE) rate was similar with tirzepatide and dulaglutide, at 7.2% and 7.0%, respectively, but more patients in the tirzepatide than the dulaglutide arm discontinued treatment due to AEs (2.9 vs 0.7%). There were also more hypoglycemic events reported in the tirzepatide group than in the dulaglutide group (23.8 vs 11.2%), but no cases of severe hypoglycemia and no treatment-related deaths were reported in either group.
Kwan et al say that “[w]hen evaluating patients with inadequate glycemic control on submaximal therapeutic doses of diabetes medications, clinicians face the decision of whether to escalate current therapies or add or switch to other medications.”
The SURPASS-SWITCH results “suggest that escalating dulaglutide is not as effective in reducing HbA1c and may further delay diabetes control than switching to tirzepatide.”
However, the authors acknowledge that factors other than HbA1c level, such as cardiovascular risk, tolerability, and cost, may also need to be considered when deciding whether to escalate or switch medication
They conclude: “Further research is needed to assess the potential benefit of early glycemic control via early medication switching on longer-term clinical outcomes.”
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