355-OR: Effects of a Six-Week Intervention with Glucagon-Like Peptide-1 Analogue on Pancreatic Volume, Edema, and DNA Synthesis in Obese Men
Authors: SVANE MARIA S. , JOHANNESEN HELLE H. , MARTINUSSEN CHRISTOFFER , BOJSEN-MOLLER KIRSTINE N. , HANSEN MARTIN L. , HANSEN ADAM E. , DEACON CAROLYN F. , HARTMANN BOLETTE , KELLER SUNE H. , KLAUSEN THOMAS L. , LOFT ANNIKA , KJAER ANDREAS , MADSBAD STEN , LÖFGREN JOHAN O. , HOLST JENS J. , WEWER ALBRECHTSEN NICOLAI J. 
Published: June 2020

Plasma concentrations of the two pancreatic enzymes, amylase and lipase, are increased within the normal physiological range after initiation of glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment. An association between the use of GLR-1RA and incidence of acute pancreatitis or pancreatic cancer has not been found - neither in rodent studies nor in preclinical studies or in the large cardiovascular outcome trials with GLP-1RAs. The increased concentrations of pancreatic enzymes have been suggested to be explained by increased DNA or protein synthesis found in rodent and acinar cell studies. However, whether this translates into humans is unknown. We therefore investigated the effect of liraglutide, a GLP-1RA, on pancreatic volume, edema and DNA synthesis reflected by 18F-flourothymidine (FLT)-uptake using state-of-the-art positron emission tomography (PET)-magnetic resonance imaging (MRI) before initiation, after four weeks during titration of liraglutide and after six weeks during steady state on maximum dose of liraglutide 3.0 mg in 14 obese men (age 38 ± 3 years, BMI 32 ± 1 kg/m2) without diabetes. Plasma concentrations of amylase and lipase were assessed in parallel. Amylase (+7 U/L [95% confidence intervals, 3 - 11] p&lt;0.01) and lipase (+19 U/L [7-30] p&lt;0.01) increased during liraglutide treatment while body weight decreased (-4.5 kg [-5,9 - -3,1] p&lt;0.01). Pancreatic volume did not change from baseline to steady state of treatment (+2.1 cm3 [-10 - 14] p=0.72]) and no signs of change in cellular infiltration of the pancreas were found (p=0.22). During titration of liraglutide, FLT-uptake increased (+0.09 g/mL [0.000 - 0.17], p=0.05).

In conclusion, six weeks of treatment with liraglutide did not affect pancreatic volume, edema or cellularity in obese individuals. Increased DNA synthesis reflected by FLT-uptake in the pancreas seen after four weeks of liraglutide treatment may be responsible for the increase in pancreatic enzymes.

Disclosure

M.S. Svane: None. H.H. Johannesen: None. C. Martinussen: None. K.N. Bojsen-Moller: None. M.L. Hansen: None. A.E. Hansen: None. C.F. Deacon: Employee; Spouse/Partner; Merck & Co., Inc. Stock/Shareholder; Spouse/Partner; Merck & Co., Inc. Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novartis AG, Novo Nordisk A/S. B. Hartmann: None. S.H. Keller: None. T.L. Klausen: None. A. Loft: None. A. Kjaer: None. S. Madsbad: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. J.O. Löfgren: 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. N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S, Novo Nordisk Foundation. Speaker’s Bureau; Self; Merck Sharp & Dohme Corp.