351-OR: Six-Day Subcutaneous GIP Infusion Increases Glycemic Time-in-Range in Patients with Type 1 Diabetes

Abstract

The glucagonotropic effect of glucose-dependent insulinotropic polypeptide (GIP) during insulin-induced hypoglycemia in patients with type 1 diabetes (T1D) prompted us to investigate the effect of a 6-day subcutaneous (sc) GIP infusion on glucose variability in patients with T1D. In a randomized, placebo-controlled, double-blinded, crossover study, 20 men with T1D (age [mean± SD] 26±8 years, BMI 23.8±1.8 kg/m2, HbA1c 51±10 mmol/mol), underwent 2 × 6 days of continuous sc GIP (6 pmol/kg/min) and placebo (saline) infusion, respectively, with an interposed 7-day washout period. Participants wore a continuous glucose monitoring system. GIP significantly increased daytime time in range (3.9-7.8 mmol/L) by [mean±SEM] 104±69 min/day (P=0.035) without statistically significant effects on time below range (<3.9 mmol/L), time above range (>10.1 mmol/L), mean glucose or hypoglycemic events. Compared to placebo, GIP increased hepatic fat content by 12.6±4.2 percentage points (assessed by FibroScan®) (P=0.006), decreased 24-hour systolic and diastolic blood pressure by 4.6±2.8 (P=0.001) and 2.6±1.3 mmHg (P=0.028), respectively, and increased heart rate by 4.4±2.0 beats per minute (P=0.002) (Figure). Compared to placebo, a 6-day sc GIP infusion in patients with T1D increased glycemic time in range and hepatic fat content and reduced systolic and diastolic blood pressure while increasing heart rate. Disclosure S.M. Nguyen Heimbürger: None. B. Hoe: None. C.N. Nielsen: None. N.C. Bergmann: Employee; Self; Zealand Pharma A/S. B. Hartmann: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. J. Størling: None. T. Vilsbøll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp & Dohme Corp., Sanofi. T.F. Dejgaard: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. M.B. Christensen: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Norgine B.V., Novo Nordisk A/S. Funding The Leona M. and Harry B. Helmsley Charitable Trust (2018PG-T1D037)