Glucagon-like peptide-1 receptor agonists and pancreatitis: a meta-analysis of randomized clinical trials.
OBJECTIVE
Several randomized trials with metabolic outcomes have reported that glucagon like peptide-1 receptor agonists (GLP-1 RA) could be associated with an increased risk of pancreatitis. The present meta-analysis aimed to examine this hypothesis.


METHODS
An extensive Medline, Embase, and Cochrane Database search for "exenatide", "liraglutide", "albiglutide", "taspoglutide", "dulaglutide", "lixisenatide", and "semaglutide" was performed up to March 31st, 2013.


METHODS
(i) randomized trials, (ii) duration ≥12 weeks; (iii) on type 2 diabetes; and (iv) comparison of GLP-1RA with placebo or active drugs. Mantel-Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for pancreatitis.


RESULTS
80 eligible trials were identified. Of these, 39 had not disclosed their findings or did not report any information on pancreatitis. The remaining 41 trials enrolled 14,972 patients, with a total exposure of 14,333 patient × years (8353 and 5980 patient × years for GLP-1 receptor agonists and comparators, respectively). The overall risk of pancreatitis was not different between GLP-1RA and comparators (MH-OR: 1.01[0.37; 2.76]; p = 0.99).


CONCLUSIONS
The present meta-analysis does not suggest any increase in the risk of pancreatitis with the use of GLP-1RA. However, it should be recognized that the number of observed cases of incident pancreatitis is very small and the confidence intervals of risk estimates are wide.
Section of Geriatric Cardiology and Medicine, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy.
Matteo
M
Monami
Obesity Agency, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy; Diabetes Agency, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy.
Ilaria
I
Dicembrini
Section of Geriatric Cardiology and Medicine, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy.
Camilla
C
Nardini
Section of Geriatric Cardiology and Medicine, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy.
Irene
I
Fiordelli
Diabetes Agency, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy. Electronic address: edoardo.mannucci@unifi.com.
Edoardo
E
Mannucci
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000069450:Liraglutide; D010195:Pancreatitis / Q000139:chemically induced*; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018027:Receptors, Glucagon / Q000819:agonists*; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use; D000067758:Glucagon-Like Peptide-2 Receptor
D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C000593833:GLP1R protein, human; C541736:taspoglutide; C534611:rGLP-1 protein; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor
Glucagon like peptide-1 receptor agonists; Meta-analysis; Pancreatitis