Summary

Metformin and dolutegravir can be co-administered safely in most patients, though dolutegravir may slightly increase metformin plasma concentrations. This interaction is generally considered clinically insignificant and does not typically require dose adjustments.

Introduction

Metformin is a first-line oral antidiabetic medication belonging to the biguanide class, primarily used to treat type 2 diabetes mellitus by reducing hepatic glucose production and improving insulin sensitivity. Dolutegravir is an integrase strand transfer inhibitor (INSTI) antiretroviral medication used in the treatment of HIV-1 infection, often prescribed as part of combination antiretroviral therapy (cART).

Mechanism of Interaction

The interaction between metformin and dolutegravir occurs through inhibition of organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) by dolutegravir. These transporters are responsible for metformin's renal elimination. When dolutegravir inhibits these transporters, it can reduce metformin clearance, leading to a modest increase in metformin plasma concentrations (approximately 15-20% increase in AUC).

Risks and Symptoms

The clinical significance of this interaction is generally low to moderate. The slight increase in metformin exposure may theoretically increase the risk of metformin-associated side effects, including gastrointestinal symptoms (nausea, diarrhea, abdominal discomfort) and, rarely, lactic acidosis. However, clinical studies have not demonstrated significant increases in adverse events when these medications are co-administered in patients with normal kidney function.

Management and Precautions

Routine dose adjustments of metformin are typically not necessary when initiating dolutegravir therapy. Monitor patients for increased metformin-related side effects, particularly gastrointestinal symptoms, during the first few weeks of co-administration. Ensure proper kidney function monitoring, as both medications require dose adjustments in renal impairment. Consider more frequent blood glucose monitoring initially to assess glycemic control. Patients should be counseled to report any unusual symptoms, particularly signs of lactic acidosis (muscle pain, difficulty breathing, stomach pain, dizziness, or weakness).

Metformin interactions with food and lifestyle

Alcohol consumption should be limited or avoided while taking metformin, as alcohol can increase the risk of lactic acidosis, a rare but serious side effect. Excessive alcohol intake can also affect blood sugar control and may increase the risk of hypoglycemia when combined with metformin. Patients should discuss alcohol consumption with their healthcare provider to determine safe limits. Additionally, metformin should be taken with food to reduce gastrointestinal side effects such as nausea, vomiting, and diarrhea. Taking metformin with meals can help improve tolerance and absorption of the medication.

Dolutegravir interactions with food and lifestyle

Dolutegravir should be taken with food when co-administered with certain medications that may reduce its absorption. However, dolutegravir can generally be taken with or without food when used alone or with most other HIV medications. Alcohol does not have clinically significant interactions with dolutegravir, but patients should consume alcohol in moderation as part of overall HIV care. Calcium, iron, magnesium, and aluminum-containing supplements or antacids should be taken either 2 hours before or 6 hours after dolutegravir to avoid reduced absorption.