Objective

• We evaluated the HRQoL of adults recently diagnosed with T2D (within 4 years) treated with tirzepatide 15 mg or MTD, or ICC, in SURPASS-EARLY over a 2-year timeframe.

Conclusions

• In addition to the primary findings of improved HbA1c and weight, ¹ tirzepatide treatment significantly improved overall physical and psychosocial health and functioning, and weight-related quality of life after 2 years of treatment, specifically the ability to perform daily activities and self-perception, compared with existing treatment options in adults who initiated treatment early in the course of T2D in the SURPASS-EARLY trial
• Although diabetes management focuses on the prevention of complications via control of glucose levels, weight, cardiovascular risk, and cardiorenal damage, ² improving and maintaining health-related quality of life may be of equal importance to patients

Limitations

• The PROs were administered in a clinical trial setting; therefore, results may not reflect those that may be observed in a real-world setting
• The open-label study design may have influenced participants to over or underestimate their treatment assessments based on their beliefs regarding assigned treatment

Introduction

• The UKPDS longitudinal study identified a 'legacy effect' in which early glycemic control following the diagnosis of T2D led to long-term improvement in key clinical outcomes ^3–5
• Tirzepatide is a long-acting dual GIP/GLP-1 RA for the treatment of T2D ⁶ and obesity ⁷ that has shown greater improvement in glycemic control than GLP-1 RAs in clinical trials of T2D ^8,9
• SURPASS-EARLY was designed to test the hypothesis that initiation of tirzepatide early after T2D diagnosis could establish better and more durable glycemic control than ICC over a 4-year planned study ¹

Methods – Study Design

• A Phase 4, randomized, open-label, parallel-group, multicenter, multinational study of the long-term efficacy and safety of tirzepatide vs. ICC
• Adults diagnosed with T2D within the last 4 years, inadequately controlled with diet, exercise, and metformin were randomized (1:1) to tirzepatide 15 mg or MTD, or ICC, for 4 years
• ICC treatments included a range of GLMs approved for the treatment of T2D (except tirzepatide) in accordance with guidelines and local product labels. Dosing was individualized to safely achieve optimal glycemic control (within a non-diabetic range)
• Primary endpoint was change from baseline in HbA1c (%) (non-inferiority) at Week 104; key secondary endpoints included change from baseline in weight (kg) (superiority) at Week 104
• HRQoL was measured at baseline and Weeks 56 and 104 using four PRO measures

Methods – Statistical Analyses

• PRO analyses were performed on the randomized population using data prior to treatment discontinuation and without use of rescue medication (efficacy estimand)
• MMRMs assessed changes from baseline to Weeks 56 and 104, for each PRO measure: IWQOL-Lite-CT, SF-36v2, APPADL, and IW-SP
• Only randomized participants with a non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in the analysis
• IWQOL-Lite-CT composite and total, and APPADL and IW-SP total raw scores were transformed to a score from 0–100 and positive changes in scores indicate better outcomes for all PRO measures

Results

• In SURPASS-EARLY, 794 participants were randomized to study treatment (398 to tirzepatide 15 mg or MTD, and 396 to ICC) ¹
• At baseline, mean (SD) age was 53.5 (10.3) years, T2D duration was 2.6 (1.6) years, HbA1c was 7.81 (0.82)%, and BMI was 35.4 (5.5) kg/m² ; 50.6% of participants were male, 81.5% were white, and 45.9% were of Hispanic or Latino ethnicity
• At Week 104, the ICC medications were GLP-1 RAs (85.3%), SGLT-2 inhibitors (16.7%), SUs (3.2%), insulin (2.6%), and DPP4 inhibitors (2.0%)
• Tirzepatide 15 mg or MTD was superior to ICC for change from baseline in HbA1c at Week 104 (ETD -0.79%, 95% CI -0.94, -0.64; p<0.001) and for change from baseline in weight at Week 104 (ETD -9.3, 95% CI -10.8, -7.9; p<0.001)

Key Results

Participants in the tirzepatide 15 mg or MTD group had improved transformed IWQOL-Lite-CT composite and total scores vs. baseline and vs. participants in the ICC group at Weeks 56 and 104 (all p<0.05).

Tirzepatide 15 mg or MTD improved SF-36v2 Physical Functioning and Role-Physical domain scores vs. baseline and vs. ICC at Weeks 56 and 104; General Health improved vs. baseline and ICC at Week 56 and vs. baseline at Week 104; Bodily Pain improved vs. baseline at Week 56 (all p<0.05).

Participants in the tirzepatide 15 mg or MTD group had improved SF-36v2 Vitality and Mental Health domain scores vs. baseline at Weeks 56 and 104 (all p<0.05), but not vs. participants in the ICC group; improvements in the Social Functioning and Role-Emotional domains were significant vs. baseline at Week 56 but not at Week 104, or vs. ICC at either timepoint

Participants in the tirzepatide 15 mg or MTD group had improved SF-36v2 PCS scores vs. baseline, and vs. participants in the ICC group, at Weeks 56 and 104 (both p<0.05); the SF-36v2 MCS score was only improved vs. baseline in the tirzepatide group at Week 56 (p<0.05).

Participants in the tirzepatide 15 mg or MTD group had improved transformed APPADL and IW-SP total scores vs. baseline and vs. participants in the ICC group at Weeks 56 and 104 (all p<0.05).