Tirzepatide-induced Weight Loss in Overweight or Obese Midlife Adults with and without Type 2 Diabetes: A Real-world Comparative Cohort Study.

BACKGROUND: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist, has demonstrated robust weight loss and glycemic benefits in randomized controlled trials. However, real-world data comparing its effectiveness and tolerability in obese adults with and without type 2 diabetes (T2D) are limited. The present study aimed to evaluate the real-world short-term effectiveness and safety of tirzepatide in promoting weight loss among obese or overweight adults with and without T2D. METHODS: This was a 12-week, prospective, observational cohort study involving 93 adults (70 individuals without diabetes and 23 individuals with T2D) receiving tirzepatide at a tertiary care center. The primary outcome was change in body weight. The secondary outcomes included changes in body mass index (BMI), waist circumference (WC), glycemic parameters (in individuals with T2D only), responder thresholds (≥5%, ≥10%, and ≥15% weight loss), and adverse events (AEs). Between-group comparisons were adjusted using multivariable regression and 1:3 propensity score matching. RESULTS: Both the groups experienced significant reductions in weight, BMI, and WC (all< 0.001). The mean weight loss was - 7.14 kg in individuals without diabetes and - 5.87 kg in individuals with T2D. Among individuals with T2D, HbA1c and fasting glucose decreased by - 1.16% and - 30.9 mg/dL, respectively. A ≥10% weight loss was achieved by 21.4% of individuals without diabetes compared with 0% of individuals with T2D (= 0.018). Adjusted between-group differences in weight change were modest and not statistically significant after propensity matching. AEs were more common in the T2D group (78.3% vs. 50.0%,= 0.033) and were primarily mild gastrointestinal symptoms. CONCLUSION: Tirzepatide produced meaningful weight loss in both T2D and non-T2D obese adults, with additional glycemic improvements in T2D. Individuals without diabetes were more likely to achieve ≥10% weight loss, while tolerability remained acceptable in both the groups. These real-world findings support tirzepatide's role in individualized obesity and metabolic disease management.