Two-year trial finds tirzepatide outperforms intensified care in early type 2 diabetes

In adults diagnosed with type 2 diabetes within the previous four years and not at their blood sugar goal on metformin, the drug tirzepatide lowered A1c and body weight substantially more than intensified conventional care over two years, according to results of the SURPASS-EARLY trial ^[1].

The trial enrolled 794 adults at 78 sites in 10 countries, all with at most four years of type 2 diabetes history and inadequate glycemic control on diet, exercise and metformin ^[1]. Participants were randomly assigned to tirzepatide — given once weekly at 15 mg or at the maximum dose they could tolerate — or to intensified conventional care, a real-world approach that allowed other GLP-1 receptor agonists but excluded tirzepatide and was guided by local treatment guidelines ^[1]. The study was open-label, meaning participants and investigators knew which treatment was being given ^[1].

Tirzepatide is sold in the United States as Mounjaro for type 2 diabetes and as Zepbound for weight management.

The primary goal was to show tirzepatide was not inferior to intensified conventional care for A1c change at two years; the trial then tested whether it was superior ^[1]. It was. A1c fell by an average of 1.99 percentage points with tirzepatide, compared with 1.32 percentage points with intensified conventional care, an estimated difference of 0.68 percentage points favoring tirzepatide ^[1]. Weight fell 8.0 kg more and waist circumference fell 6.2 cm more with tirzepatide than with the comparison regimen ^[1]. All three differences were statistically significant, with P values below 0.001 ^[1].

Normoglycemia — defined in the trial as an A1c below 5.7 percent — was reached by 60.2 percent of participants taking tirzepatide, compared with 24.0 percent of those receiving intensified conventional care ^[1]. The most common adverse events in both groups were gastrointestinal ^[1]. The researchers list the open-label design as a limitation, and the trial was funded by Eli Lilly and Company, which makes tirzepatide ^[1].

Why it matters for patients

Most people with type 2 diabetes start treatment with metformin, and additional drugs are usually added step by step if A1c stays high. This trial tested a different sequence: using a dual GIP/GLP-1 receptor agonist early, within four years of diagnosis, rather than escalating conventional therapy first ^[1].

The comparison was not a placebo. The intensified conventional care group could receive other GLP-1 receptor agonists, so the results reflect a difference between two active treatment strategies rather than between a drug and no treatment ^[1]. That is a higher bar, and it is one reason the size of the weight and A1c gaps may draw attention.

The trial enrolled only people who had been diagnosed within the past four years, so the findings may not describe what happens in someone who has lived with type 2 diabetes for a decade or more. The study also did not report whether participants were able to stop diabetes medications, and whether the differences in A1c, weight and waist circumference translate into fewer heart, kidney or eye complications over time has not been reported ^[1].

Cost and insurance coverage were not addressed in the results, and it is not known whether the findings will change treatment guidelines or drug labeling.

What happens next

The trial is registered as NCT05433584 ^[1]. Results beyond the two-year mark have not been reported, and no further milestones for this study have been disclosed. People currently deciding between an early injectable and stepped-up standard care still have to weigh the two-year differences shown here against factors the trial did not measure, including price, coverage and long-term outcomes.