Drug interaction of DPP4 Inhibitors with some drugs precipitates Hypoglycemia: Study
Dipeptidyl peptidase-4 inhibitors (DPP-4i's), also known as gliptins, are among the newest categories of antidiabetic medications (ADMs). The major benefit of DPP 4 Inhibitors is that it helps to achieve glycemic control without weight gain and have rare hypoglycemic events. However, a recent study warns that DPP4 inhibitors in combination with certain concomitant medication are associated with an increased risk of hypoglycemia. The study findings were published in the frontiers in Pharmacology on 15 April 2021.
Since type 2 diabetes mellitus (T2DM) patients often have comorbid conditions such as cardiovascular diseases requiring the use of additional antihypertensive or antihyperlipidemic agents, it is important to ascertain that the risks of drug-drug interactions when multiple medications are prescribed together. However, little is known about drug-drug interactions between DPP-4i′s and concurrent medications. Therefore, Dr Chin-Ying Ray and his team conducted a study to investigate the drug-drug interactions between DPP-4i′s and commonly concurrent medications, measure the frequency of such co-prescriptions, and describe the associated risk of hypoglycemia in the co-prescribed medications.
In this retrospective study, the researchers included data of 77,047 patients using DPP-4i′s for T2DM from the Chang Gung Research database provided by Chang Gung Memorial Hospital. After reviewing the medical literature for studies describing drug-drug interactions between commonly prescribed medications and DPP-4i′s, the researchers included bumetanide, captopril, colchicine, acetaminophen, cotrimoxazole, and pantoprazole for analysis. The major outcome assessed was hypoglycemia which was determined as necessitating infusion of 2 or more 20-mL ampules of 50% glucose or injection of 1 mg glucagon. They used a generalized estimating equation–based Poisson model for statistical analysis.
Key findings of the study were:
- The researchers noted that the most common medications co-prescribed with DPP4is over all person-quarters were acetaminophen, simvastatin, fluvastatin, and colchicine (all >20,000 person-quarters).
- In follow-up through 31 May 2018, they observed 13,546 hypoglycemia events in 694,300 person-quarters with DPP-4i prescriptions.
- Upon analysis, they found that the combinations of a DPP-4i with bumetanide, captopril, colchicine, acetaminophen, cotrimoxazole, and pantoprazole were associated with an increased risk of hypoglycemia.
- Compared with person-quarters of DPP-4i use alone, they found that the adjusted hypoglycemia rate ratios per 100 person-years were significantly greater for:
◊ Bumetanide: 2.44,
◊ Captopril: 2.97,
◊ Colchicine: 1.87,
◊ Acetaminophen: 2.83,
◊ Cotrimoxazole: 2.27,
◊ Pantoprazole: 3.03.
The authors concluded, "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."
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