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

Abstract

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. 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. Randomized, open-label, parallel-group, phase 4 trial (SURPASS-EARLY). (ClinicalTrials.gov: NCT05433584). 78 sites in 10 countries. 794 adults with at most 4 years of T2D history treated with metformin. 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. The primary objective was to show the noninferiority of tirzepatide to ICC for change in hemoglobin A_1c (HbA_1c) from baseline to 2 years. Secondary objectives were to show the superiority of tirzepatide for change in HbA_1c, weight, and waist circumference. Tirzepatide was superior to ICC for mean changes from baseline to 2 years in HbA_1c (-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]; <i>P</i> < 0.001), weight (ETD, -8.0 kg [CI, -9.39 to -6.50 kg]; <i>P</i> < 0.001), and waist circumference (ETD, -6.2 cm [CI, -7.54 to -4.93 cm]; <i>P</i> < 0.001) (treatment regimen estimand). More participants achieved normoglycemia (HbA_1c <5.7%) with tirzepatide (60.2%) than ICC (24.0%). The most common adverse events were gastrointestinal in both groups. Open-label design. In participants with early T2D uncontrolled with metformin, tirzepatide treatment resulted in superior reductions in HbA_1c, weight, and waist circumference, and more participants achieved normoglycemia (HbA_1c <5.7%) with tirzepatide than ICC after 2 years. Eli Lilly and Company.