Impact of GLP-1 receptor agonists on major gastrointestinal disorders for type 2 diabetes mellitus: a mixed treatment comparison meta-analysis.
OBJECTIVE
We aimed to integrate evidence from all randomized controlled trials (RCTs) and assess the impact of different doses of exenatide or liraglutide on major gastrointestinal adverse events (GIAEs) in type 2 diabetes (T2DM).


METHODS
RCTs evaluating different doses of exenatide and liraglutide against placebo or an active comparator with treatment duration ≥4 weeks were searched and reviewed. A total of 35, 32 and 28 RCTs met the selection criteria evaluated for nausea, vomiting, and diarrhea, respectively. Pairwise random-effects meta-analyses and mixed treatment comparisons (MTC) of all RCTs were performed.


RESULTS
All GLP-1 dose groups significantly increased the probability of nausea, vomiting and diarrhea relative to placebo and conventional treatment. MTC meta-analysis showed that there was 99.2% and 85.0% probability, respectively, that people with exenatide 10 μg twice daily (EX10BID) was more vulnerable to nausea and vomiting than those with other treatments. There was a 78.90% probability that liraglutide 1.2 mg once daily (LIR1.2) has a higher risk of diarrhea than other groups. A dose-dependent relationship of exenatide and liraglutide on GIAEs was observed.


CONCLUSIONS
Our MTC meta-analysis suggests that patients should be warned about these GIAEs in early stage of treatment by GLP-1s, especially by EX10BID and LIR1.2, to promote treatment compliance.
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing 100191, China.
Feng
F
Sun
Kai
K
Yu
Zhirong
Z
Yang
Shanshan
S
Wu
Yuan
Y
Zhang
Luwen
L
Shi
Linong
L
Ji
Siyan
S
Zhan
D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000077270:Exenatide; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000069450:Liraglutide; D009325:Nausea / Q000139:chemically induced; D016017:Odds Ratio; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D018027:Receptors, Glucagon / Q000819:agonists; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced
D000077270:Exenatide; C000593833:GLP1R protein, human; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms