MON-721 - Comparative Effectiveness of Tirzepatide Versus Semaglutide in Obese Non-Diabetic Adults: A Retrospective Cohort Study.

Background
Glucagon Like Peptide -1 (GLP-1) receptor agonists are widely used for managing obesity and improving glycemic control in diabetes. Weight loss of 5-10% reduces obesity-related complications and improves quality of life, while greater weight loss with GLP-1 RAs demonstrated 20% reduction in major cardiovascular events in non-diabetic patients (1). Recent evidence shows that patients with hypothyroidism who lose more than 5 lb after starting a GLP-1 medication experience an average 0.36 - 0.55 mIU/L reduction in TSH levels.

Methods:
A retrospective cohort study of 50 non-diabetic adults with obesity (BMI ≥30 kg/m²) on GLP-1 receptor agonists was conducted at an outpatient clinic. After screening 200 patients, 50 met inclusion criteria (HbA1c < 6.5%, normal thyroid function or treated hypothyroidism with stable thyroid function, no concurrent anti-obesity medications). Patients on semaglutide (n=25, up to 2.4 mg weekly) were compared to those on tirzepatide (n=25, up to 15 mg weekly). The primary outcome was mean weight change at 12 months. Secondary outcomes included BMI reduction, HbA1c change, TSH suppression, and adverse events.

Results:
Tirzepatide demonstrated superior weight loss compared to semaglutide (mean weight loss: 37.1 lb vs 20.2 lb; mean BMI reduction: -6.13 kg/m² vs -3.39 kg/m²; p< 0.001). Mean HbA1c reduction was comparable (-0.31% vs -0.28%). TSH reduction occurred proportionally to weight loss in both groups, with greater reductions observed in trizepatide cohort (mean -0.8 to -1.3 mIU/L) compared with semaglutide cohort (mean -0.25 to -0.55 mIU/L), with stable free T4 levels. Treatment persistence was markedly higher with tirzepatide (67%) versus semaglutide (13%). Insurance/cost barriers caused discontinuation in 47% of semaglutide versus 21% of tirzepatide patients. Metformin co-administration was present in 33% of patients. GI-related discontinuation was lower with tirzepatide (8%) versus semaglutide (12%). Weight regain after discontinuation was universal and rapid (50-67% regain within 3-6 months) in both groups, emphasizing the need for long -term management strategies.

Conclusion:
In obese non-diabetic adults, tirzepatide produced significantly greater weight loss and superior treatment persistence compared to semaglutide at 12 months. TSH suppression reflected physiological adaptation to weight loss rather than drug-induced thyroid dysfunction. Insurance barriers were the primary driver of treatment failure, highlighting the need for improved access to effective therapies.

References:
1. Rodriguez, P. J., Goodwin Cartwright, B. M., Gratzl, S., et al. (2024). Semaglutide vs tirzepatide for weight loss in adults with overweight or obesity. JAMA Internal Medicine, 184(9), 1056-1064.

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