Tirzepatide Versus Intensified Conventional Care After 2 Years of Treatment in Early Type 2 Diabetes : A Randomized Clinical Trial.

BACKGROUND: Initiation of treatment with tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist (GLP-1RA), early after a diagnosis of type 2 diabetes (T2D) may establish better and more durable glycemic control than current treatment approaches per guidelines and clinical practice. OBJECTIVE: To assess the efficacy and safety of tirzepatide versus intensified conventional care (ICC) in participants with early T2D who have inadequate glycemic control with diet, exercise, and metformin. DESIGN: Randomized, open-label, parallel-group, phase 4 trial (SURPASS-EARLY). (ClinicalTrials.gov: NCT05433584). SETTING: 78 sites in 10 countries. PARTICIPANTS: 794 adults with at most 4 years of T2D history treated with metformin. INTERVENTION: Tirzepatide (15 mg or maximum tolerated dose) or ICC (including GLP-1RAs but excluding tirzepatide) used in clinical practice and supported by local treatment guidelines. MEASUREMENTS: The primary objective was to show the noninferiority of tirzepatide to ICC for change in hemoglobin A (HbA) from baseline to 2 years. Secondary objectives were to show the superiority of tirzepatide for change in HbA, weight, and waist circumference. RESULTS: Tirzepatide was superior to ICC for mean changes from baseline to 2 years in HbA (-1.99 percentage points [95% CI, -2.12 to -1.87 percentage points] vs. -1.32 percentage points [CI, -1.44 to -1.19 percentage points]; estimated treatment difference [ETD], -0.68 percentage points [CI, -0.84 to -0.51 percentage points];  < 0.001), weight (ETD, -8.0 kg [CI, -9.39 to -6.50 kg];  < 0.001), and waist circumference (ETD, -6.2 cm [CI, -7.54 to -4.93 cm];  < 0.001) (treatment regimen estimand). More participants achieved normoglycemia (HbA <5.7%) with tirzepatide (60.2%) than ICC (24.0%). The most common adverse events were gastrointestinal in both groups. LIMITATION: Open-label design. CONCLUSION: In participants with early T2D uncontrolled with metformin, tirzepatide treatment resulted in superior reductions in HbA, weight, and waist circumference, and more participants achieved normoglycemia (HbA <5.7%) with tirzepatide than ICC after 2 years. PRIMARY FUNDING SOURCE: Eli Lilly and Company.