Tirzepatide-Like GIP Addition to Semaglutide Shows No Added Benefit, suggests study
A study published in The Lancet Diabetes & Endocrinology revealed that adding glucose-dependent insulinotropic polypeptide (GIP) to semaglutide did not significantly improve glycemic control in people with type 2 diabetes over 6 weeks. There were no significant improvements in mean glucose on continuous glucose monitoring, HbA1c, body weight, blood pressure, or heart rate, suggesting limited short-term benefit from combining GIP activity with semaglutide.
This research from the Center for Clinical Metabolic Research in Hellerup enrolled 61 adults with type 2 diabetes who met specific eligibility criteria, including stable diabetes treatment, an HbA1c level between 6.5% and 10.5%, and a body mass index (BMI) ranging from 25 to 50 kg/m². Participants were randomly assigned to one of four treatment groups: placebo plus placebo, placebo plus GIP, semaglutide plus placebo, or semaglutide plus GIP.
The trial involved an 8-week run-in period during which participants received either semaglutide or placebo, followed by 6 weeks of continuous GIP or placebo infusion while maintaining their assigned weekly injections. The primary objective was to determine whether GIP could improve average blood glucose levels over a 14-day monitoring period at the end of the 14-week study.
When compared to placebo, GIP alone did not produce the prespecified reduction in mean glucose levels, while combining GIP with semaglutide also failed to provide any additional glycemic benefit over semaglutide alone. The treatment target of a 1.50 mmol/L reduction in glucose levels was not achieved in either comparison.
The study included participants with a median age of 64 years, an average BMI of 31.6 kg/m², and a median diabetes duration of just over six years. Although fasting concentrations of both intact and total GIP increased substantially in participants receiving GIP infusions, these higher hormone levels did not translate into improved glucose regulation.
Safety findings indicated that injection-site reactions were the most frequently reported adverse event, affecting more than one-third of participants. Gastrointestinal side effects, including nausea and related symptoms, were more common among participants receiving semaglutide, regardless of whether GIP was added. The study experienced a 16% dropout rate, limiting the strength of conclusions regarding GIP as a standalone treatment.
Source:
Helsted, M. M., Fonnesbech-Wulff, C., Schaltz, N. L., Lund, I. W., Forman, J. L., Nielsen, C. K., Englund, A., Hartmann, B., Vilsbøll, T., Holst, J. J., Lund, A. B., Christensen, M. B., Knop, F. K., & Gasbjerg, L. S. (2026). Effects of a 6-week subcutaneous infusion of native GIP alone or as add-on to semaglutide in people with type 2 diabetes: a single-centre, double-blind, parallel-group, randomised, placebo-controlled trial. The Lancet. Diabetes & Endocrinology, 14(7), 581–593. https://doi.org/10.1016/S2213-8587(26)00075-6
