medwireNews: People taking dipeptidyl peptidase (DPP)-4 inhibitors to treat type 2 diabetes may have an increased risk for cholecystitis, especially with longer duration of treatment, show findings of a meta-analysis.
“[A]s the duration of prescriptions for dipeptidyl peptidase-4 inhibitors is usually longer in routine practice than in clinical trials, awareness of the role of treatment duration might be of great clinical importance,” write the researchers in The BMJ.
However, Huabing Zhang (Peking Union Medical College Hospital, Beijing, China) and study co-authors stress that the absolute risk increase was small and “should be weighed against the benefits of dipeptidyl peptidase-4 inhibitor treatment.”
The researchers included 82 randomized controlled trials in a traditional pairwise meta-analysis, finding a significant 43% increased risk for cholecystitis with DPP-4 inhibitor versus control treatment, which amounted to an additional 15 cases per 10,000 person–years.
This elevated risk was evident among people treated for at least 26 weeks, at a significant 1.51-fold risk increase, but not among those treated for less time. DPP-4 inhibition was not associated with an increased risk for cholelithiasis or biliary diseases.
Zhang and colleagues say that DPP-4 inhibitors “enhance the bioavailability of endogenous glucagon-like peptide-1 and glucose dependent insulinotropic polypeptide, both of which might affect postprandial gallbladder motility” and increase the risk for gallbladder or biliary disease.
They also note that treatment with the glucagon-like peptide (GLP)-1 receptor agonist liraglutide has previously been linked to an increased risk for gallbladder or biliary disease.
The team also conducted a network meta-analysis involving 184 trials, which showed that DPP-4 inhibitor treatment was associated with a significant 1.55-fold increased risk for cholecystitis relative to treatment with sodium-glucose cotransporter (SGLT)2 inhibitors.
But the risk for cholecystitis was no higher with DPP-4 inhibitors than with GLP-1 receptor agonists, which themselves were associated with a significantly increased risk for cholecystitis relative to SGLT2 inhibitors (odds ratio=1.46) and controls/other medications (odds ratio=1.37).
Given this, the study authors caution that their “findings may be also extended to double or triple agonists, including glucagon-like peptide-1, glucose dependent insulinotropic polypeptide, or both.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group