Incretin Therapies in Type 1 Diabetes: Reappraisal and Geriatric Considerations

A narrative review in Diabetology synthesizes experimental, clinical trial, and real-world evidence on incretin hormones (GLP-1 and GIP) and incretin-based therapies used adjunctively with insulin in adults with type 1 diabetes.

The authors focus on two categories: GLP-1 receptor agonists (GLP-1RAs) and the dual GIP/GLP-1 agonist tirzepatide. Across the summarized studies, they report HbA1c changes of about 0.2% to 0.8% and GLP-1RA-associated weight changes of roughly 3.6 to 8.8 kg. The review catalogs safety signals and highlights evidence gaps, including a need for large-scale, adequately powered randomized controlled trials to confirm long-term efficacy and safety.

For GLP-1RAs in type 1 diabetes, the authors describe glycemic effects that generally trend toward modest improvement, with the magnitude varying by study design, agent, and population. Weight outcomes are summarized as generally favoring loss across the studies compiled, and the review also notes reductions in insulin requirements when GLP-1RAs are added to background insulin therapy. The authors describe subgroup patterns without presenting them as universal, including larger glycemic benefit in people with detectable C-peptide and in those with overweight or insulin-resistant phenotypes. Overall, GLP-1RA outcomes are presented as directionally similar across reports but not uniform from trial to trial.

Evidence for tirzepatide is summarized as more limited in type 1 diabetes than for GLP-1RAs, but the authors highlight short-term reports of body weight change of approximately −10.3 to −10.6 kg over 6 months in relevant cohorts. Alongside weight change, the review describes insulin-sparing observations, including early and marked reductions in total daily insulin in some cohorts using pump-based or automated insulin delivery systems, without presenting a single pattern that applies to all settings. The authors also note that direct comparative data between tirzepatide and GLP-1RAs in type 1 diabetes are not established in the evidence they summarize.

On tolerability and adverse events, the review compiles heterogeneous safety signals reported when incretin agents are used alongside insulin in type 1 diabetes. In randomized settings described by the authors, including the ADJUNCT studies of liraglutide, symptomatic hypoglycemia and hyperglycemic episodes with ketosis were reported in some trial arms, while other trials and real-world series summarized in the review did not identify the same pattern. Gastrointestinal adverse effects are presented as commonly reported across incretin-based therapies, and the authors also mention modest increases in heart rate in trial reports. Overall, safety findings are framed as mixed and dependent on study context and monitoring conditions.

The authors foreground evidence limitations and research priorities, emphasizing that available type 1 diabetes data are constrained by sample size and follow-up in several reports, with additional heterogeneity across protocols and study populations. They reiterate a call for large-scale, adequately powered randomized controlled trials to confirm long-term efficacy and safety. The review also discusses practical considerations for selected individuals with type 1 diabetes, including potential risks described in relation to titration approaches and structured patient education. The authors conclude by again calling for larger trials designed to address these gaps.

Key Takeaways:

• Across the studies summarized by the authors, adjunctive GLP-1 receptor agonist use in adults with type 1 diabetes was associated with modest HbA1c changes and weight reduction, with results varying by study.
• The review summarizes short-term tirzepatide reports showing larger weight reductions in relevant type 1 diabetes populations, with reductions in insulin requirements described in some cohorts.
• The authors highlight heterogeneous hypoglycemia/ketosis signals, common gastrointestinal side effects, and limited geriatric generalizability, alongside their call for standardized protocols and geriatric-focused endpoints in future trials.