What is the regimen for adding metformin (Metformin) to insulin therapy?

From the Guidelines

When adding metformin to an insulin regimen, start with a low dose of 500 mg daily and increase the dose every 2 weeks, as tolerated, if the eGFR is ≥45 mg/dL. This approach is based on the most recent guidelines from the 2023 standards of care in diabetes 1. The key consideration is to initiate metformin at a dose that minimizes gastrointestinal side effects while effectively complementing insulin therapy.

Key Considerations for Metformin Initiation

• The patient's eGFR should be ≥45 mg/dL to start metformin at 500 mg daily, with dose increases every 2 weeks as tolerated.
• If the eGFR is <45 mg/dL, or if the patient is already taking metformin or cannot tolerate it, a second-line agent should be considered.
• Monitoring of blood glucose levels is crucial during the initiation and titration of metformin, as insulin requirements may decrease.
• The combination of metformin and insulin is beneficial for patients with type 2 diabetes, as it improves insulin sensitivity and potentially reduces insulin doses.

Adjusting Insulin Doses with Metformin

• Insulin doses, particularly prandial insulin, may need to be adjusted downward to avoid hypoglycemia as metformin takes effect.
• The guidelines suggest titrating the dose of basal insulin based on fasting fingerstick glucose test results over a week, with specific adjustments for fasting glucose levels above or below target ranges 1.
• For patients on premixed insulin, if the mealtime insulin dose is ≤10 units/dose, discontinuing prandial insulin and adding a noninsulin agent like metformin is recommended, with titration of prandial insulin doses down as the noninsulin agent doses are increased.

From the Research

Regimen for Adding Metformin to Insulin Therapy

The regimen for adding metformin to insulin therapy involves several key considerations:

• Starting patients with type 2 diabetes on insulin therapy using once-daily injections of biphasic insulin aspart 70/30, biphasic human insulin 70/30, or NPH insulin in combination with metformin 2
• Patients can safely and effectively begin insulin therapy using once-daily injections of biphasic insulin aspart 70/30, biphasic human insulin 70/30, or NPH insulin in combination with metformin 2
• Continuing metformin when starting insulin in patients with Type 2 diabetes can decrease weight gain, lower insulin requirement, and improve glycaemic control 3

Key Findings

• A study found that metformin was associated with less weight gain than placebo, a greater reduction in HbA1c, and a lower insulin requirement 3
• Another study found that once-daily metformin and vildagliptin combination was associated with significant reductions in plasma glucose and HbA1c 4
• Insulin 70/30 mix plus metformin was found to be as effective as triple oral therapy in lowering A1C and FPG values, and was more cost-effective 5

Treatment Considerations

• The combination of metformin and insulin can target both insulin resistance and insulin deficiency 6
• Fixed dose combination tablets of metformin and other medications can improve patient adherence and offer an inexpensive and more efficacious option 6
• The regimen should be tailored to the individual patient's needs and response to treatment, with regular monitoring of glucose levels and adjustment of medication as needed 2, 3