Work

Tirzepatide as Adjunct to Insulin in Adults With Type 1 Diabetes and Overweight or Obesity: A Systematic Review of Randomized and Real‐World Evidence

Year: 2026

Type: review

Abstract: BACKGROUND: Overweight and obesity are increasingly common in adults with type 1 diabetes (T1D), contributing to insulin resistance, higher insulin requirements, and greater cardiometabolic burden. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has shown major metabolic benefits in type 2 diabetes and obesity, but its role in T1D remains unclear. This systematic review evaluated tirzepatide as adjunctive therapy to insulin in adults with T1D and overweight or obesity. METHODS: This review followed PRISMA 2020 and was registered in PROSPERO (CRD420261335230). PubMed/MEDLINE, Embase, Scopus, Web of Science Core Collection, and ClinicalTrials.gov were searched from inception to March 1, 2026. Eligible studies included randomized and observational studies reporting efficacy or safety outcomes of tirzepatide added to insulin in adults with T1D. Because of marked clinical and methodological heterogeneity, findings were synthesized qualitatively without meta-analysis, and certainty of evidence was assessed using a GRADE-based framework. RESULTS: Eight studies were included: one small 12-week phase 2 randomized placebo-controlled trial and seven observational studies, most at serious risk of bias. The most consistent finding was body weight reduction. In the randomized trial, tirzepatide reduced mean body weight by 10.3 kg, with an estimated treatment difference of 8.7 kg versus placebo, corresponding to an 8.8% reduction from baseline. A placebo-adjusted 35.1% reduction in total daily insulin dose and a between-group HbA1c difference of -0.4 percentage points were also reported, although glycaemic findings were short-term and imprecise. Gastrointestinal adverse events were the most frequent safety findings. Evidence certainty was low or very low. CONCLUSIONS: Tirzepatide may be a promising investigational adjunct in selected adults with T1D and overweight or obesity, particularly for weight reduction. However, current evidence remains insufficient to establish durable glycaemic benefit or long-term safety. Larger randomized trials are needed.

Source: Endocrinology Diabetes & Metabolism

DOI: 10.1002/edm2.70225

Authors: Giuseppina Alessia Acucella, Danilo Caponio

Institution: University of Bari Aldo Moro

Language: English

Topic: Diabetes Management and Research

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,280