Evaluation of the concurrent use of dolutegravir and metformin in human immunodeficiency virus-infected patients

Abstract

An analysis of the interaction between dolutegravir and metformin was conducted in the HIV ambulatory clinic setting. This was a multicenter, retrospective case series evaluating adult, HIV-infected patients concurrently prescribed dolutegravir and metformin. Historical electronic medical records were utilized to collect case-specific data. Laboratory parameters including serum creatinine (SCr), hemoglobin A1c (HgbA1c), plasma HIV RNA, CD4 cell count, and lactate were reviewed. Adverse drug reactions were assessed using patient-reported gastrointestinal intolerance and hypoglycemic symptoms. Metformin dose reduction or discontinuation was also recorded. Nineteen patients identified as concurrently taking metformin and dolutegravir were included. Eighteen patients were on metformin prior to dolutegravir initiation, with 13 having received metformin for at least six months prior to dolutegravir. At the time of dolutegravir initiation, one patient had a preemptive metformin dose reduction. Seven patients were initiated on dolutegravir with a metformin dose greater than 1000 mg daily. Eleven patients had baseline and three- to six-month follow-up HgbA1c. Of those 11 patients, eight had stable or decreased values. Thirteen of the 19 patients had an increase in SCr, with a median increase of 0.3 mg/dl (0.03-0.43). Gastrointestinal distress (N = 3) and hypoglycemic symptoms (N = 3) were reported in a total of five patients. Adverse drug reactions resulted in metformin dose reduction (N = 2) and/or discontinuation (N = 2). There were no reported cases of lactic acidosis. Providers concurrently prescribing dolutegravir and metformin should be aware of potential consequences with this combination and may consider an empiric metformin dose reduction to prevent intolerable adverse drug reactions.

Update on Adverse Effects of HIV Integrase Inhibitors

“…DTG has an excellent profile in terms of drug interactions. Metformin constitutes one of the exceptions, with a significant increase in metformin levels when co-administered with DTG [60]. This should prompt clinicians to closely monitor lactic acidosis symptoms when prescribing both drugs and US Prescribing Information suggests limiting the total daily dose of metformin to 1000 mg.…”

Metformin inhibits expression of the proinflammatory biomarker inducible nitric oxide synthase in hepatocytes

“…Many studies, ranging from basic to clinical studies, have been conducted on metformin and its clinical applications in treating various diseases [37][38][39][40][41]. Recent reports suggest that metformin may have the therapeutic potential to treat liver injury [42,43], in addition to its efficacy in treating type 2 diabetes [44].…”

Pharmacokinetic drug interactions of integrase strand transfer inhibitors

“…Previous studies showed that both BIC and DTG increased metformin plasma exposure in healthy adults and the dose adjustment of metformin is recommended to maintain optimal blood glucose control ( Song et al., 2016b ; Custodio et al., 2017 ). There were no severe adverse effects such as lactic acidosis reported when dolutegravir and metformin were co-prescribed to HIV patients but evaluating concurrent use of metformin and DTG case by case should still be considered ( Masich et al., 2017 ; Naccarato et al., 2017 ).…”