What's the next step for a patient with elevated Hemoglobin A1c (HbA1c) on maximum doses of metformin (Metformin) and Victoza (Liraglutide), and 7 units (U) of Humalog (Insulin Lispro) three times a day (TID)?

From the Guidelines

For a patient with elevated HbA1c despite being on maximum doses of metformin, liraglutide (Victoza), and 7 units of insulin lispro (Humalog) three times daily, the next step would be to intensify insulin therapy by adding basal insulin, as recommended by the most recent guidelines 1. The patient's current regimen is not sufficient to achieve optimal glycemic control, and adding basal insulin will provide 24-hour insulin coverage to control overnight and fasting glucose levels.

• The basal insulin dose should be initiated at 10 units once daily at bedtime, as suggested by the 2025 standards of care in diabetes 1.
• The dose should be titrated by increasing by 2 units every 3-4 days until fasting blood glucose reaches 80-130 mg/dL, with careful monitoring for hypoglycemia, following an evidence-based titration algorithm 1.
• It is essential to assess the adequacy of the insulin dose at every visit and consider clinical signals to evaluate for overbasalization and the need for adjunctive therapies, such as GLP-1 RA or dual GIP and GLP-1 RA, if A1C remains above goal 1.
• Regular blood glucose monitoring is crucial during this transition to avoid hypoglycemic episodes, and the patient should be educated on the signs and symptoms of hypoglycemia and how to treat it, using glucose tablets or carbohydrate-containing foods or beverages, as recommended by the nutrition therapy guidelines 1.
• If glycemic targets remain unmet after optimizing basal insulin, consider referral to an endocrinologist for potential adjustment of the insulin regimen, evaluation of insulin-to-carbohydrate ratios, or consideration of an insulin pump.

From the FDA Drug Label

5 mg, as add-on to titrated basal insulin glargine (with or without metformin). In this open-label comparator trial (double-blind with respect to TRULICITY dose assignment) with primary endpoint at 26 weeks, 884 adult patients on 1 or 2 insulin injections per day were enrolled Randomization occurred after a 9-week lead-in period; during the initial 2 weeks of the lead-in period, patients continued their pre-trial insulin regimen but could be initiated and/or up-titrated on metformin, based on investigator discretion; this was followed by a 7-week glycemic stabilization period prior to randomization At randomization, patients discontinued their pre-trial insulin regimen and were randomized to TRULICITY 0.75 mg once weekly, TRULICITY 1. 5 mg once weekly, or insulin glargine once daily, all in combination with prandial insulin lispro 3 times daily, with or without metformin.

The next step for a patient with elevated Hemoglobin A1c (HbA1c) on maximum doses of metformin and Victoza, and 7 units of Humalog three times a day could be to consider adding basal insulin or switching to a different medication regimen.

• Dulaglutide (TRULICITY) has been shown to be effective in reducing HbA1c when used in combination with basal insulin and prandial insulin, with or without metformin 2.
• However, the patient is currently taking Victoza (Liraglutide), which is a different medication, and the FDA label does not provide direct information on switching from Victoza to Dulaglutide.
• The patient's current regimen of metformin and Victoza is already maximized, and the addition of Humalog is not sufficient to achieve adequate glycemic control.
• Considering the patient's elevated HbA1c, a more intensive insulin regimen or the addition of a new medication class may be necessary to achieve better control. However, the provided information does not directly address the next steps for this specific patient, and clinical judgment should be used to determine the best course of action.

From the Research

Patient Background

• The patient is currently taking the maximum dose of metformin and Victoza (Liraglutide), as well as 7 units of Humalog (Insulin Lispro) three times a day.
• The patient has an elevated Hemoglobin A1c (HbA1c) level.

Next Steps for Better Control

• According to the study 3, for patients with type 2 diabetes mellitus (T2DM), insulin is considered alone or in combination with oral agents when HbA1c is ≥ 7.5% (≥ 58 mmol/mol).
• The study 4 suggests that basal insulin is usually initiated at a conservative dose of 10 units/day or 0.1-0.2 units/kg/day, then titrated thereafter based on patients' self-measured fasting plasma glucose.
• The study 5 indicates that insulin administration is strongly considered for people with T2D with HbA1c levels exceeding 9.0% and 10%, respectively.
• However, the study 5 also suggests that glucagon-like peptide-1 (GLP-1) receptor agonists (RA) may offer superior benefit compared to insulin, especially for patients with HbA1c > 9%.
• The study 6 provides an updated review of head-to-head clinical studies on GLP-1 RA, demonstrating that all GLP-1 RA agents are effective therapeutic options at reducing A1C, but differences exist in terms of magnitude of effect on A1C and weight as well as frequency of adverse effects.

Considerations for Insulin Therapy

• The study 3 recommends that metformin combined with insulin is associated with decreased weight gain, lower insulin dose, and less hypoglycemia when compared with insulin alone.
• The study 7 suggests that basal insulin analogues with a reduced peak profile and an extended duration of action are preferred, and that rapid-acting prandial analogues are preferred over regular human insulin for prandial glycemic control.
• Frequent blood glucose measurements and patient education on insulin dosing based on carbohydrate counting, premeal blood glucose, and anticipated physical activity are paramount 7.