Abstract
Background: Dipeptidylpeptidase-4 inhibitors (DPP-4i′s) are considered to be safe for patients with type 2 diabetes mellitus (T2DM). However, little is known about drug–drug interactions between DPP-4i′s and concurrent medications. Methods: Data on patients using DPP-4i′s for T2DM during 2011–2017 were retrieved from Chang Gung Research database provided by Chang Gung Memorial Hospital. Patients were excluded if they were aged <30 years or >90 years; had incomplete demographic data; had insulinoma; or had records of concomitant insulin use. A generalized estimating equation–based Poisson model was employed for statistical analysis. The primary outcome was hypoglycemia events. Results: We retrieved data on a total of 97,227 patients using DPP-4i′s. After patients were excluded according to the mentioned criteria, the remaining 77,047 DPP-4i users were studied (mean age 64 ± 12 years, men 54.4%). The most common medications coprescribed with DPP4is over all person-quarters were acetaminophen, simvastatin, fluvastatin, and colchicine (all >20,000 person-quarters). The combinations of a DPP-4i with bumetanide, captopril, colchicine, acetaminophen, cotrimoxazole, and pantoprazole were associated with an increased risk of hypoglycemia. Compared with the ratios observed for person-quarters of DPP-4i use alone (reference category), the adjusted prevalence ratios per 100 person-years of hypoglycemia for person-quarters of DPP-4i use in combination with bumetanide, captopril, colchicine, acetaminophen, cotrimoxazole, and pantoprazole were 2.44 (95% confidence interval [CI], 1.78–3.36), 2.97 (95% CI, 2.26–3.90), 1.87 (95% CI, 1.44–2.42), 2.83 (95% CI, 2.44–3.29), 2.27 (95% CI, 1.27–4.04), and 3.03 (95% CI, 1.96–4.68), respectively. Conclusion: Among patients taking DPP-4i′s for T2DM, concurrent use of such inhibitors with bumetanide, captopril, acetaminophen, and pantoprazole was associated with an increased risk of hypoglycemia compared with the use of DPP-4i′s alone. Physicians prescribing DPP-4i′s should consider the potential risks associated with their concomitant use with other drugs.
Highlights
Therapeutic armamentaria for the treatment of type 2 diabetes mellitus (T2DM) have been increasingly diversified in mechanism of actions in recent decades
Data on 97,227 patients with T2DM taking DPP-4i′s were retrieved from the Chang Gung Research Database (CGRD) for the period 2011–2017
Combinations of a DPP-4i with bumetanide, captopril, acetaminophen, and pantoprazole were associated with an increased risk of hypoglycemia
Summary
Therapeutic armamentaria for the treatment of type 2 diabetes mellitus (T2DM) have been increasingly diversified in mechanism of actions in recent decades. Preclinical studies with DPP-4i′s pharmacokinetic interactions have described with some of commonly coprescribed medications, including diuretics, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, statins, antibiotics, and proton pump inhibitors, with DPP-4i′s (Kim et al, 2006; Ayalasomayajula et al, 2007; Chu et al, 2007; He et al, 2008; Patel et al, 2011; Patel et al, 2011; Arulmozhiraja et al, 2016; May and Schindler, 2016) The knowledge of these scientific hypotheses in the laboratory cannot supplant clinical scenarios where drug-drug interactions may be far more complicated what is known from translational medicine. Little is known about drug–drug interactions between DPP-4i′s and concurrent medications
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
