The effect of 6-day subcutaneous glucose-dependent insulinotropic polypeptide infusion on time in glycaemic range in patients with type 1 diabetes: a randomised, double-blind, placebo-controlled crossover trial
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Aims/hypothesis: Type 1 diabetes is characterised by reduced glucagon response to hypoglycaemia, increasing the risk of insulin treatment-associated hypoglycaemia known to hamper glycaemic control. We previously reported a glucagonotropic effect of exogenous glucose-dependent insulinotropic polypeptide (GIP) during insulin-induced hypoglycaemia in individuals with type 1 diabetes. Here we investigate the effect of a 6-day s.c. GIP infusion on time in glycaemic range as assessed by continuous glucose monitoring (CGM) in individuals with type 1 diabetes. Methods: In a randomised, placebo-controlled, double-blind crossover study, time in glycaemic range (assessed by double-blinded CGM) was evaluated in 20 men with type 1 diabetes (18–75 years, stable insulin treatment ≥3 months, diabetes duration 2–15 years, fasting plasma C-peptide below 200 pmol/l, BMI 20–27 kg/m2, HbA1c <69 mmol/mol [8.5%]) during two × 6 days of continuous s.c. GIP (6 pmol kg−1 min−1) and placebo (saline [154 mmol/l NaCl]) infusion, respectively, with an interposed 7-day washout period. The primary outcome was glycaemic time below range, time in range and time above range. Results: There were no significant differences in time below range (<3.9 mmol/l, p = 0.53) or above range (>10 mmol/l, p = 0.32) during night-time or daytime, in mean glucose, or in hypoglycaemic events as assessed by CGM. GIP altered neither self-reported hypoglycaemia nor safety measures. Compared with placebo, GIP significantly increased time in tight range (3.9–7.8 mmol/l) during daytime (06:00–23:59 hours) by [mean ± SEM] 11.2 ± 5.1% [95% CI 0.41, 21.9] (p = 0.02). Conclusions/interpretation: Six-day s.c. GIP infusion in men with type 1 diabetes did not procure convincing effect on overall time in range, but increased time in tight glycaemic range during daytime by ~2 h per day. Trial registration: ClinicalTrials.gov NCT03734718. Funding: The study was funded by grants from The Leona M. and Harry B. Helmsley Charitable Trust and Aase og Ejnar Danielsens Fond. Graphical abstract: [Figure not available: see fulltext.]
|Status||E-pub ahead of print - 2021|
SMNH has been an invited speaker at AstraZeneca. JJH has served on advisory boards for Novo Nordisk and Merck Sharp & Dohme. TV has served on scientific advisory panels or speakers’ bureaus or has served as a consultant to or received research support from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Gilead, Merck Sharp & Dohme, Mundipharma, Novo Nordisk, Sanofi and SunPharma. TFD has received lecture fees from Boehringer Ingelheim, Novo Nordisk and AstraZeneca and research support from AstraZeneca and Novo Nordisk. FKK has served on scientific advisory panels or speaker’s bureaus or has served as a consultant to or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, MedImmune, Merck Sharp & Dohme, Mundipharma, Norgine, Novo Nordisk, Sanofi and Zealand Pharma. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their contribution to this manuscript.
The study was funded by unrestricted grants from The Leona M. and Harry B. Helmsley Charitable Trust and Aase og Ejnar Danielsens Fond. The funders of the study had no role in study design, data collection, data analysis or data interpretation.
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.