Date of report 04 Jul 2024
Reported case interaction between
Dolutegravir and METFORMIN
Dolutegravir and METFORMIN
Drugs suspected to be involved in the DDI
Complete list of drugs taken by the patient
Metformin 850 mg BID; enalapril 20 mg BID; rosuvastatin 40 mg QD
Clinical case description
A 58-year-old female with HIV infection diagnosed in 2016. No liver and kidney function impairment. Current BMI 32.7 kg/m2 (obese). On ART with DTG/3TC (50/300 mg) QD. She was diagnosed with metabolic syndrome (hyperglycemia, hypertension and dyslipidemia), and she was prescribed metformin 850 mg BID. Soon after, she experienced nausea, flatulence and diarrhea. No other symptoms that could be early signs of lactic acidosis (i.e., vomiting, weakness, muscle pain, chills, drowsiness, abdominal pain or discomfort, slow or irregular heartbeat, breathing difficulty) were reported by the patient.
A consultation with the HIV specialist was made. Since dolutegravir is an inhibitor of the renal organic cation transporters (OCT)2 and multidrug and toxin extrusion transporter (MATE)1, it may increase plasma concentrations of other drugs eliminated via OCT2 or MATE1 such as metformin. Although these side effects reported by the patient are common with metformin, their severity may have been enhanced by co-administration with dolutegravir. After consultation, metformin was changed to semaglutide 1.0 mg subcutaneously once a week, with resolution of the side effects.
Clinical Outcome
Drug Interaction Probability Scale (DIPS)
Editorial Comment
This is a case of a potential drug-drug interaction between dolutegravir and metformin due to inhibition of OCT2 and MATE1 by dolutegravir. Co-administration of metformin with dolutegravir (50 mg QD) increased metformin AUC and Cmin by 79% and 66%. While hypoglycemia has been rarely reported, an observational study in 19 participants receiving both drugs reported gastrointestinal distress (n=3) and hypoglycemic symptoms (n=3) that resulted in metformin dose reduction (n=2) and/or discontinuation (n=2) (Masich A, et al. Int J STD AIDS 2017;28(12):1229-1233. doi: 10.1177/0956462417695995.). A maximum dose of metformin of 1000 mg daily is advised when co-administered with dolutegravir, as well as monitoring for possible side effects.
University of Liverpool Recommendation
Potential interaction - may require close monitoring, alteration of drug dosage or timing of administration