Achieving durable glycemic control early in the course of type 2 diabetes mellitus (T2DM) remains challenging in routine clinical practice. The phase 4 SURPASS-EARLY trial, published in the Annals of Internal Medicine, evaluated tirzepatide versus intensified conventional care (ICC) in adults with early T2DM inadequately controlled with diet, exercise, and metformin. 

The randomized, open-label, parallel-group trial enrolled 794 adults across 78 sites in 10 countries who had a T2D duration of 4 years or less. Participants received tirzepatide 15 mg or the maximum tolerated dose, or ICC based on local treatment guidelines and clinical practice, including GLP-1RAs but excluding tirzepatide. The primary endpoint assessed noninferiority for change in hemoglobin A1c (HbA1c) from baseline to 2 years. Secondary endpoints evaluated superiority for HbA1c, body weight, and waist circumference changes. 

Findings

• Mean HbA1c reduction at 2 years was greater with tirzepatide than ICC. HbA1c decreased by −1.99 percentage points (95% CI, −2.12 to −1.87) with tirzepatide and by −1.32 percentage points (95% CI, −1.44 to −1.19) with ICC. The estimated treatment difference (ETD) was −0.68 percentage points (95% CI, −0.84 to −0.51; P < 0.001).
• Tirzepatide resulted in greater body weight reduction than ICC. The ETD for weight change was −8.0 kg (95% CI, −9.39 to −6.50; P < 0.001).
• Waist circumference reduction was also greater with tirzepatide. The ETD was −6.2 cm (95% CI, −7.54 to −4.93; P < 0.001).
• Normoglycemia, defined as HbA1c below 5.7%, was achieved in 60.2% of participants receiving tirzepatide compared with 24.0% receiving ICC.
• Gastrointestinal adverse events were the most commonly reported adverse events in both groups.

The study found that tirzepatide provided greater improvements in glycemic control, body weight, and waist circumference than intensified conventional care over 2 years in adults with early T2DM receiving metformin.