Tirzepatide vs Intensified Conventional Care at 2 Years in Early T2D

Key Takeaways

• Tirzepatide was associated with greater reductions in HbA1c, weight, and waist circumference than intensified conventional care over 2 years.
• More participants achieved normoglycemia with tirzepatide than with intensified conventional care, at 60.2% versus 24.0%.
• Gastrointestinal adverse events were the most common in both groups, and the open-label design was the stated limitation.

After 2 years, adults with early type 2 diabetes taking metformin had a mean HbA1c change of -1.99 percentage points with tirzepatide and -1.32 with intensified conventional care. The randomized trial enrolled adults early in the course of diabetes who were already receiving metformin-based therapy. It compared tirzepatide with intensified conventional care used in usual practice over the same follow-up period. Body weight and waist circumference were assessed alongside glycemic change. After 2 years of treatment, tirzepatide was associated with greater glycemic and anthropometric improvements than intensified conventional care.

The SURPASS-EARLY trial was a randomized, open-label, parallel-group, phase 4 study conducted at 78 sites in 10 countries. It enrolled 794 adults with at most 4 years of type 2 diabetes history who were treated with metformin and had inadequate glycemic control with diet, exercise, and metformin. Participants were assigned to tirzepatide 15 mg or the maximum tolerated dose or to intensified conventional care used in clinical practice and supported by local treatment guidelines. Intensified conventional care could include GLP-1 receptor agonists but excluded tirzepatide, preserving a comparator distinct from the study drug. The primary objective was to show noninferiority of tirzepatide to intensified conventional care for HbA1c change from baseline to 2 years, and secondary objectives included superiority for HbA1c, weight, and waist circumference at the same time point.

At 2 years, under the treatment regimen estimand, tirzepatide was superior to intensified conventional care for HbA1c, weight, and waist circumference. For HbA1c, the estimated treatment difference was -0.68 percentage points, with a 95% CI of -0.84 to -0.51 and P < 0.001. Weight had an estimated treatment difference of -8.0 kg, with a 95% CI of -9.39 to -6.50 and P < 0.001. Waist circumference had an estimated treatment difference of -6.2 cm, with a 95% CI of -7.54 to -4.93 and P < 0.001. More participants also reached normoglycemia with tirzepatide.

The most common adverse events were gastrointestinal in both groups. The open-label design was the stated limitation for interpreting the randomized comparison. The randomized population consisted of adults with at most 4 years of diabetes history who remained on metformin background therapy. Across 2 years of follow-up, tirzepatide was associated with greater reductions in HbA1c, weight, and waist circumference, along with more normoglycemia, than intensified conventional care.