Safety of native glucose-dependent insulinotropic polypeptide in humans
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Safety of native glucose-dependent insulinotropic polypeptide in humans. / Helsted, Mads M.; Schaltz, Nina L.; Gasbjerg, Lærke S.; Christensen, Mikkel B.; Vilsbøll, Tina; Knop, Filip K.
In: Peptides, Vol. 177, 171214, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Safety of native glucose-dependent insulinotropic polypeptide in humans
AU - Helsted, Mads M.
AU - Schaltz, Nina L.
AU - Gasbjerg, Lærke S.
AU - Christensen, Mikkel B.
AU - Vilsbøll, Tina
AU - Knop, Filip K.
N1 - Publisher Copyright: © 2024 Elsevier Inc.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - GIP(1−42)
KW - GLP-1
KW - glucose metabolism
KW - incretins
KW - safety
KW - type 2 diabetes
U2 - 10.1016/j.peptides.2024.171214
DO - 10.1016/j.peptides.2024.171214
M3 - Journal article
C2 - 38615716
AN - SCOPUS:85190608671
VL - 177
JO - Peptides
JF - Peptides
SN - 0196-9781
M1 - 171214
ER -
ID: 389505944