ABSTRACT:
Tirzepatide provides superior efficacy in weight reduction and metabolic control compared to existing therapies. The present systematic review assessed the effect of Tirzepatide on the risk of developing type 2 diabetes mellitus (T2DM) among people living with obesity or overweight. Six major databases [MEDLINE (PubMed),
ClinicalTrials.gov
, EMBASE, Scopus, Web of Science and Cochrane Library] were searched for potential studies published till 10 July 2025. Two‐stage dual screening with third‐person adjudication was adopted for screening of studies. PROSPERO ID: CRD42024614466. RoB 2.0 and the Newcastle‐Ottawa Scale were used to assess the quality of randomised controlled trials (RCTs) and cohort studies, respectively. Database search yielded 2601 studies, among which three studies were eligible (one RCT and two cohort studies) for systematic review. The hazard ratio (HR) for the new‐onset diabetes at 12 months following the Tirzepatide intake was significantly lower than that of the Semaglutide group of patients (HR = 0.73,
p
< 0.001 [95% CI: 0.58–0.92]). The risk of the new‐onset diabetes for 176 weeks (HR = 0.07,
p
< 0.001 [95% CI: < 0.01–0.1]) and 193 weeks (HR = 0.12,
p
< 0.001 [95% CI: 0.1–0.2]) following the Tirzepatide intake was significantly lower than that of the placebo group of patients. Tirzepatide might have significant efficacy in the prevention of T2DM in patients with obesity or overweight.