What additional interventions can be considered for a patient with uncontrolled diabetes mellitus (DM) despite insulin therapy?

From the Guidelines

For patients with uncontrolled diabetes despite insulin therapy, adding non-insulin medications such as metformin or GLP-1 receptor agonists, optimizing insulin regimens, and implementing lifestyle modifications are crucial interventions to improve glycemic control. When considering additional interventions, it's essential to prioritize those that have the most significant impact on morbidity, mortality, and quality of life. According to the most recent and highest quality study 1, GLP-1 receptor agonists are preferred over insulin for their ability to enhance glucose control while promoting weight loss and reducing the risk of hypoglycemia. Some key considerations include:

• Adding metformin (starting at 500mg daily, increasing to 1000mg twice daily as tolerated) to improve insulin sensitivity 1
• Using GLP-1 receptor agonists like semaglutide (0.25mg weekly, titrating to 0.5-1mg) or dulaglutide (0.75-1.5mg weekly) to enhance glucose control and promote weight loss 1
• Optimizing insulin regimens by adjusting basal-bolus ratios or considering insulin pump therapy to improve glycemic control 1
• Implementing lifestyle modifications, including consistent carbohydrate counting, regular physical activity (150 minutes weekly of moderate exercise), and maintaining a consistent meal schedule 1
• Addressing potential barriers such as insulin technique errors, missed doses, or psychological factors like diabetes distress 1 These interventions work through different mechanisms to achieve better glycemic control when insulin alone is insufficient. It's also important to consider the patient's individual needs and preferences when selecting additional interventions, as noted in the 2017 American Diabetes Association standards of medical care in diabetes 1. Ultimately, the goal is to improve glycemic control, reduce morbidity and mortality, and enhance quality of life for patients with uncontrolled diabetes despite insulin therapy.

From the Research

Additional Interventions for Uncontrolled Diabetes Mellitus (DM)

For patients with uncontrolled diabetes mellitus (DM) despite insulin therapy, several additional interventions can be considered:

• Combination therapy: Adding new oral glucose-lowering drugs to insulin, such as DPP-4 inhibitors, SGLT-2 inhibitors, or GLP-1 receptor agonists, can lead to improved glycemic control 2, 3.
• Lifestyle modifications: Emphasizing the importance of lifestyle changes, including diet and exercise, can help achieve better management of diabetes 4.
• Phytoconstituents: Considering the use of phytoconstituents as multitargeting molecules and potential therapeutic adjuvants to first-line hypoglycemic agents 4.
• Treatment persistence and adherence: Addressing poor treatment persistence and adherence, which can be barriers to glycemic control, by simplifying treatment regimens, improving convenience, and alleviating patient fears of adverse effects 5.
• Insulin therapy optimization: Optimizing insulin therapy by using basal insulin analogs, fixed ratio combinations with GLP-1 receptor agonists, or rapid-acting insulins via the inhaled route 2, 3.

Specific Medications and Therapies

Some specific medications and therapies that can be considered as add-on treatments to insulin include:

• GLP-1 receptor agonists: Can significantly reduce HbA1c levels, body weight, and basic insulin dosage, but may increase the risk of hypoglycemia 3.
• SGLT-2 inhibitors: Can significantly reduce HbA1c levels and body weight, but may increase the risk of genital tract infections 2, 3.
• DPP-4 inhibitors: Can significantly reduce HbA1c levels and fasting plasma glucose levels, with a lower risk of hypoglycemia compared to GLP-1 receptor agonists 3.