Safety of native glucose-dependent insulinotropic polypeptide in humans

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2024-07, Vol.177, p.171214, Article 171214
• Main Authors: Helsted, Mads M., Schaltz, Nina L., Gasbjerg, Lærke S., Christensen, Mikkel B., Vilsbøll, Tina, Knop, Filip K.
• Format: Article
• Language: English
• Subjects: Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Gastric Inhibitory Polypeptide; GIP(1−42); GLP-1; Glucose Intolerance - metabolism; glucose metabolism; Humans; incretins; Peptide Fragments; safety; type 2 diabetes
• ISSN: 0196-9781; 1873-5169; 1873-5169
• DOI: 10.1016/j.peptides.2024.171214

In this systematic review, we assessed the safety and possible safety events of native glucose-dependent insulinotropic polypeptide (GIP)(1−42) in human studies with administration of synthetic human GIP. We searched the PubMed database for all trials investigating synthetic human GIP(1−42) administration. A total of 67 studies were included. Study duration ranged from 30 min to 6 days. In addition to healthy individuals, the studies included individuals with impaired glucose tolerance, type 2 diabetes, type 1 diabetes, chronic pancreatitis and secondary diabetes, latent autoimmune diabetes in adults, diabetes caused by a mutation in the hepatocyte nuclear factor 1-alpha gene, end-stage renal disease, chronic renal insufficiency, critical illness, hypoparathyroidism, or cystic fibrosis-related diabetes. Of the included studies, 78% did not mention safety events, 10% of the studies reported that no safety events were observed in relation to GIP administration, and 15% of the studies reported safety events in relation to GIP administration with most frequently reported event being a moderate and transient increased heart rate. Gastrointestinal safety events, and changes in blood pressure were also reported. Plasma concentration of active GIP(1−42) increased linearly with dose independent of participant phenotype. There was no significant correlation between achieved maximal concentration of GIP(1−42) and reported safety events. Clearance rates of GIP(1−42) were similar between participant groups. In conclusion, the available data indicate that GIP(1−42) in short-term (up to 6 days) infusion studies is generally well-tolerated. The long-term safety of continuous GIP(1−42) administration is unknown. •Intravenous administration of native GIP in human studies has been well tolerated.•Reports of safety events has been few.•The most frequently reported safety event has been increased heart rate.•Types and frequency of safety events has been similar between participant groups.