SURPASS-SWITCH finds switching beats dose escalation for people on dulaglutide

Adults with type 2 diabetes who were not meeting blood sugar goals on a lower dose of dulaglutide saw bigger improvements when they switched to tirzepatide than when their dulaglutide dose was pushed higher, according to results from the randomized SURPASS-SWITCH trial ^[1].

The study was a multicenter, randomized, open-label phase 4 trial run at 38 sites across five countries and registered as NCT05564039 ^[1]. It enrolled 282 adults, who were assigned to either switch to tirzepatide (139 people) or escalate dulaglutide (143 people) ^[1]. To take part, people had to have an HbA1c between 7.0% and 9.5%, stable body weight, a body mass index of at least 25 kg/m2, and to have been on a steady dose of dulaglutide (0.75 mg or 1.5 mg) for at least six months, plus zero to three oral diabetes medications for at least three months ^[1].

What the trial measured

The main question was how much HbA1c changed from the start of the study to week 40 ^[1]. The key secondary question was change in body weight at week 40 ^[1].

At 40 weeks, HbA1c fell 1.44 percentage points (standard error 0.07) in the group switched to tirzepatide 15 mg or their maximum tolerated dose, compared with 0.67 percentage points (standard error 0.08) in the group escalated to dulaglutide 4.5 mg or maximum tolerated dose ^[1]. That is a treatment difference of 0.77 percentage points in favor of switching (95% confidence interval, -0.98 to -0.56; P < 0.001) ^[1].

Weight change followed the same pattern. People who switched to tirzepatide lost 10.5 kg (about 23 pounds) on average, versus 3.6 kg (about 8 pounds) for those who increased dulaglutide — a difference of 6.9 kg, or roughly 15 pounds (95% confidence interval, -8.3 to -5.5 kg; P < 0.001) ^[1].

On safety, serious adverse events were reported by 10 people (7.2%) in the tirzepatide group and 10 people (7.0%) in the dulaglutide group ^[1]. The most common treatment-emergent side effects in the trial were nausea and diarrhea ^[1]. The abstract does not break out how often each side effect occurred in each group, how many people stopped treatment, or how many reached the highest tirzepatide dose, so those details are not yet known from this source.

Both drugs are once-weekly injections. Tirzepatide, sold as Mounjaro for type 2 diabetes and Zepbound for obesity, acts on both the GIP and GLP-1 receptors, while dulaglutide acts on the GLP-1 receptor alone ^[1]. The trial was funded by Eli Lilly and Company, which makes both medications ^[1].

Why it matters for patients

Many people with type 2 diabetes are already on a GLP-1 drug and still above their A1c goal. When that happens, the usual choices are to raise the current dose or move to a different medicine. SURPASS-SWITCH is one of the few head-to-head trials that tests those two options directly against each other rather than against placebo ^[1].

The results give doctors and patients specific numbers to weigh in that conversation: an extra 0.77 percentage points of A1c reduction and about 15 more pounds of weight loss over 40 weeks with the switch ^[1]. Serious adverse events were similar between the groups, at roughly 7% in each ^[1], though nausea and diarrhea were the most common side effects overall ^[1].

There are limits. The trial was open-label, meaning participants and investigators knew which drug they were taking, which the authors list as a limitation ^[1]. Everyone in the study entered on the two lower dulaglutide doses (0.75 mg or 1.5 mg), so the findings do not speak to people already taking dulaglutide 3 mg or 4.5 mg ^[1]. The trial ran 40 weeks, so longer-term durability is not addressed, and it measured A1c and weight rather than heart attacks, strokes or other hard outcomes ^[1]. It was also paid for by the company that sells both drugs ^[1].

What happens next

The full trial results were published following the trial's completion, with the abstract indexed in PubMed under PMID 40183678 ^[1]. Whether coverage rules, prior authorization requirements or supply affect the ability to switch in the United States is not addressed by this study. Anyone considering a change in diabetes medication would need to discuss it with their own clinician.