A drug-drug interaction (DDI) exists between bictegravir and metformin. Bictegravir inhibits renal organic cation transporter-2, leading to increased metformin plasma concentrations. The objective of this analysis was to evaluate the clinical implications of concomitant bictegravir and metformin administration. This was a retrospective, single-center, descriptive analysis evaluating people with human immunodeficiency virus (PWH) concurrently prescribed bictegravir and metformin between February 2018–June 2020. PWH lost to follow-up or non-adherent were excluded. Data collection included: hemoglobin A1C (HgbA1C), HIV RNA viral load, CD4 cell count, serum creatinine, and lactate. Adverse drug reactions (ADRs) were assessed by provider-documented, patient-reported symptoms of gastrointestinal (GI) intolerance and hypoglycemia. Metformin dose adjustments and discontinuations were recorded. Fifty-three PWH were included (116 screened; 63 excluded). GI intolerance was reported in three PWH (5.7%). There were no documented episodes of hypoglycemia or lactic acidosis. Five PWH had metformin dose reductions (N = 3 for unspecified reasons; N = 1 for GI intolerance) or discontinuation (N = 1 unrelated to ADRs). Both diabetes and HIV control improved (HgbA1C decreased by 0.7% with virologic control in 95% of PWH). Minimal ADRs were reported in PWH receiving concurrent metformin and bictegravir. Prescribers should be aware of this potential interaction; however, no empiric metformin total daily dose adjustment appears necessary.