Dr. Steinberg's secondary analyses of SCALE trial show that saxenda/liraglutide raises reversibly the blood levels of amalyse and lipase. The incidence of acute pancreatitis was rare, but more common in those receiving liraglutide (n=12, 0.3%) than placebo (n=1, 0.1%). About 5,000 participants were followed for one year.
Roughly 50% of acute pancreatitis cases were felt to be gallstone-mediated. No correlation between amylase/lipase levels, gallstone formation and anticipation of pancreatitis was seen. Findings suggest no need of measuring pancreatic markers in patients receiving liraglutide 1.8 or 3.0 mg daily.
Secondary analyses (SCALE)
Objective: To describe amylase/lipase activity levels and events of acute pancreatitis (AP) in the SCALE (Satiety and Clinical Adiposity—Liraglutide Evidence in individuals with and without diabetes) weight-management trials.
Research Design and Methods: Secondary analyses were performed on pooled data from four trials (N = 5,358 with BMI ≥30, or 27-30 kg/m2 with ≥1 comorbidity). Of these, 1,723 had normoglycemia, 2,789 had prediabetes, and 846 had type 2 diabetes. Participants were randomized to liraglutide 3.0 mg (n = 3,302), liraglutide 1.8 mg (n = 211, only type 2 diabetes), or placebo (n = 1,845). Relationships between characteristics and amylase/lipase activity at baseline and during treatment were investigated.
Over 56 weeks, liraglutide 3.0 mg versus placebo was associated with increases in mean levels of 7% (amylase) and 31% (lipase), respectively. Similar changes in amylase/lipase levels were observed with liraglutide 1.8 mg.
More participants receiving liraglutide 3.0 mg versus placebo experienced amylase (9.4% vs. 5.9%) and lipase (43.5% vs. 15.1%) elevations greater than or equal to the upper limit of normal (ULN); few had elevations ≥3 × ULN for amylase (<0.1% with liraglutide 3.0 mg or placebo) or lipase (2.9% vs. 1.5%). After liraglutide discontinuation, enzymes returned to baseline levels.
Thirteen participants developed acute pancreatitis: 12 on (n = 9, 0.3%) or after (n = 3, 0.1%) liraglutide 3.0 mg treatment and one (0.1%) with placebo.
A total of 6/13 participants with acute pancreatitis (5/12 liraglutide; 1 placebo) had gallstone disease evident at AP onset.
Amylase/lipase elevations either 1 × ULN or ≥3 × ULN before AP onset had very low positive predictive value (PPV) for acute pancreatitis (<1%).
Liraglutide resulted in dose-independent, reversible increases in amylase/lipase activity, unrelated to baseline characteristics, not predicting onset of acute pancreatitis.
Gallstones possibly contributed to 50% of acute pancreatitis cases.
Data provide no basis for amylase/lipase level monitoring in liraglutide treatment except in suspected acute pancreatitis.