Research Summary

Tirzepatide Treatment Improves Glycemic Control, Body Weight in Early Type 2 Diabetes

Ashton L. Stahl

Key Highlights

  • Tirzepatide produced greater HbA1c reductions than intensified conventional care at 104 weeks.
  • More patients receiving tirzepatide achieved normoglycemia, defined as HbA1c below 5.7%.
  • Tirzepatide also led to greater reductions in body weight and waist circumference.
  • Gastrointestinal adverse events were the most common safety findings in both groups.

Tirzepatide was superior to intensified conventional care for reducing HbA1c, body weight, and waist circumference after 2 years among adults with early type 2 diabetes that was inadequately controlled with diet, exercise, and metformin, according to findings from the SURPASS-EARLY randomized clinical trial published in Annals of Internal Medicine.

The phase 4 randomized, open-label, parallel-group trial enrolled 794 adults with type 2 diabetes diagnosed within the past 4 years, with an HbA1c of 7.0% to 9.5%, a body mass index of 25 to 45 kg/m², and stable metformin use. Participants were randomly assigned 1:1 to tirzepatide, administered once weekly up to 15 mg or the maximum tolerated dose, or intensified conventional care, which could include guideline-supported glucose-lowering medications other than tirzepatide. The study was conducted at 78 sites in 10 countries, and the reported analysis covers the prespecified 104-week time point.

Study Findings

At 104 weeks, mean HbA1c decreased by 1.99 percentage points with tirzepatide compared with 1.32 percentage points with intensified conventional care, for an estimated treatment difference of −0.68 percentage points. Tirzepatide was also superior for body weight reduction, with a mean change of −13.8 kg vs −5.9 kg, and for waist circumference, with a mean change of −11.6 cm vs −5.4 cm.

A larger proportion of participants receiving tirzepatide achieved HbA1c targets at 104 weeks. HbA1c below 7% was achieved by 86% of the tirzepatide group vs 72% of the intensified conventional care group; HbA1c below 6.5% was achieved by 80% vs 60%; and normoglycemia, defined as HbA1c below 5.7%, was achieved by 60% vs 24%. Weight loss thresholds also favored tirzepatide, with 78%, 61%, and 44% achieving at least 5%, 10%, and 15% weight loss, respectively, compared with 50%, 26%, and 12% with intensified conventional care.

Safety findings showed treatment-emergent adverse events in 74.6% of tirzepatide-treated participants and 68.6% of those receiving intensified conventional care. The most frequent adverse events were gastrointestinal, including nausea, diarrhea, constipation, vomiting, and dyspepsia, and were mostly mild to moderate. No severe hypoglycemic events were reported.

Clinical Implications

According to the study authors, the findings suggest that early intervention with tirzepatide after a type 2 diabetes diagnosis can durably improve glycemia and weight control beyond what was achieved with intensified conventional care over 2 years. The authors also stated that the full 208-week SURPASS-EARLY study will provide further insight into whether these effects are maintained through 4 years.

The study’s limitations included its open-label design, which the authors noted could introduce reporting bias, although blinding was not feasible because of the range of intensified conventional care options. The trial also excluded patients with HbA1c values substantially above 9.5%.

Expert Commentary

“These findings support the concept that early initiation of tirzepatide treatment could establish better and potentially more durable glycemic control than can be achieved with conventional care,” the researchers concluded.

Reference
Del Prato S, Heine RJ, Perez Manghi FC, et al. Tirzepatide versus intensified conventional care after 2 years of treatment in early type 2 diabetes: a randomized clinical trial. Ann Intern Med. Published online May 26, 2026. doi:10.7326/ANNALS-25-05602