Use of second-generation incretin analogs (GLP-1 and GIP receptor agonists) in type 1 diabetes and latent autoimmune diabetes in adults: A systematic review.
This systematic review examined existing evidence on the use of second-generation incretin analogs — specifically semaglutide (a GLP-1 receptor agonist) and tirzepatide (a dual GLP-1/GIP receptor agonist) — in adults with type 1 diabetes (T1D) or latent autoimmune diabetes in adults (LADA). Researchers screened 3,053 records from six major databases and ClinicalTrials.gov, ultimately identifying 11 eligible publications. These comprised two systematic reviews, one post hoc subgroup analysis, six narrative or consensus reviews, and two LADA case reports. Three key themes emerged from the synthesis: (1) LADA is frequently misdiagnosed or diagnosis is delayed due to its heterogeneous presentation; (2) both tirzepatide and semaglutide show potential benefits in LADA and in certain T1D subtypes, particularly in individuals retaining residual beta-cell function; and (3) existing clinical management frameworks may guide practice while robust trial data are awaited. The authors concluded that current evidence is promising but moderate in quality, and that well-designed, adequately powered randomized controlled trials in clearly defined LADA and T1D populations are needed to establish long-term efficacy and safety. Notable limitations include the small number of eligible studies, the predominance of review-level and narrative publications, and only two primary patient-level reports.
Why this grade: This is a systematic review synthesizing primarily review-level publications and two case reports, with no original controlled trial data; it does not itself constitute direct human clinical trial evidence.
Background Wide pathological heterogeneity exists in patients with autoimmune diabetes, typically classified as type 1 diabetes (T1D); up to half may have latent autoimmune diabetes in adults (LADA) with slower onset of beta-cell destruction. Second-generation incretin analogs may have potential benefits for these patients. Objectives A systematic review was conducted to assess existing knowledge related to the use of semaglutide or tirzepatide for T1D or LADA treatment. Data sources The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search included Ovid MEDLINE, Cochrane CENTRAL, Embase, CINAHL, Web of Science, and ClinicalTrials.gov for studies published between 1 January 2020 and 12 June 2025 involving adults with T1D or LADA treated with semaglutide or tirzepatide. Conclusions From 3,053 records screened, 11 eligible publications were selected. These included two systematic reviews, one post hoc subgroup analysis, six narrative/consensus reviews, and two LADA case reports. Three themes emerged: (1) Inconsistency and misdiagnosis or diagnostic delay of LADA; (2) Potential benefits of tirzepatide and semaglutide for LADA and certain types of T1D, and; (3) Existing approaches for clinical management. Well-designed, adequately powered randomized trials in clearly defined LADA and T1D populations are needed to clarify long-term efficacy. Implications for practice Current evidence for semaglutide and tirzepatide in T1D and LADA is promising but of moderate quality. Diagnosis and management of LADA is challenging, but potential approaches exist. Second-generation incretin analogs may provide multiple benefits for adults with autoimmune diabetes who retain residual beta-cell function.
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