No effects of a 6‐week intervention with a glucagon‐like peptide‐1 receptor agonist on pancreatic volume and oedema in obese men without diabetes

Abstract

Aim To investigate the effect of a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), liraglutide, on pancreatic volume, oedema, cellularity and DNA synthesis in humans. Materials and Methods We performed an open‐label study in 14 obese men (age 38 ± 11 years, body mass index 32 ± 4 kg/m2) without diabetes. Subjects were examined at baseline, during titration (week 4) of liraglutide towards 3.0 mg/day, and 2 weeks after steady‐state treatment (week 6) of a final dose of liraglutide. The primary endpoint was pancreatic volume determined by magnetic resonance imaging. Secondary endpoints included pancreatic oedema and cellularity, positron emission tomography‐based [18F]fluorothymidine (FLT) uptake (DNA synthesis) and plasma pancreatic enzymes. Results Plasma amylase (+7 U/L [95% confidence intervals 3‐11], P < .01) and lipase (+19 U/L [7‐30], P < .01) increased during liraglutide treatment. Pancreatic volume did not change from baseline to steady state of treatment (+0.2 cm3 [−8‐8], P = .96) and no change in pancreatic cellular infiltration was found (P = .22). During titration of liraglutide, FLT uptake in pancreatic tissue increased numerically (+0.08 [0.00‐0.17], P = .0507). Conclusions Six weeks of treatment with liraglutide did not affect pancreatic volume, oedema or cellularity in obese men without diabetes.

Glucagon‐like peptide‐1: Are its roles as endogenous hormone and therapeutic wizard congruent?

“…Much effort was subsequently made to look for mechanisms, and today it is well established that the GLP‐1 receptor is indeed expressed on the acinar cells of the pancreas [62, 105]. However, the elevation of lipase and amylase levels (which remain within normal limits) does not appear to be a signal of inflammation, but rather reflects a stimulatory effect on pancreatic protein synthesis, as shown in the mouse as well as in powerful human imaging studies [106, 107]. In agreement with these findings, treatment with GLP‐1RAs is no longer considered to be associated with an increased risk of pancreatitis in patients with T2DM, in whom the risk of this disease is already elevated compared to the background population [108].…”

“…Much effort was subsequently made to look for mechanisms, and today it is well established that the GLP-1 receptor is indeed expressed on the acinar cells of the pancreas [62,105]. However, the elevation of lipase and amylase levels (which remain within normal limits) does not appear to be a signal of inflammation, but rather reflects a stimulatory effect on pancreatic protein synthesis, as shown in the mouse as well as in powerful human imaging studies [106,107].…”

The Pharmacological Landscape for Fatty Change of the Pancreas

“…Magnetic resonance imaging revealed no signs of acute pancreatitis following 12 weeks of liraglutide use in the Dutch trial [ 37 ]. Although the other clinical studies mentioned above did not report on the occurrence of acute pancreatitis, there were no signs of this disease on magnetic resonance imaging in a study from Denmark that used liraglutide for 6 weeks (change in IPFD was not investigated) [ 39 ].…”