From the Guidelines
Worsening insulin resistance requiring increased insulin treatment is best managed by a multi-faceted approach that includes lifestyle modifications, medication adjustments, and optimization of insulin regimens, as recommended by the American Diabetes Association standards of medical care in diabetes 1.
Causes of Worsening Insulin Resistance
The causes of worsening insulin resistance include:
- Weight gain
- Physical inactivity
- Stress
- Certain medications (like steroids or antipsychotics)
- Progressive beta-cell dysfunction
- Illness or infection
- Hormonal changes
- Poor sleep
- Aging
Workup for Worsening Insulin Resistance
The workup should include:
- Comprehensive assessment of glycemic control through HbA1c testing, fasting and postprandial glucose monitoring, and evaluation of insulin dosing and adherence
- Assessment for medication side effects
- Screening for comorbidities like sleep apnea or fatty liver disease
- Checking for hormonal disorders
Treatment of Worsening Insulin Resistance
Treatment involves:
- Lifestyle modifications including weight loss (even 5-10% can significantly improve insulin sensitivity), regular exercise (150 minutes weekly of moderate activity), and dietary changes emphasizing reduced carbohydrates and processed foods
- Medication adjustments may include adding insulin-sensitizing agents like metformin (500-2000mg daily), pioglitazone (15-45mg daily), or GLP-1 receptor agonists such as semaglutide (0.25-2.0mg weekly) or dulaglutide (0.75-4.5mg weekly) 1
- Insulin regimens should be optimized, potentially switching to more physiologic basal-bolus regimens or considering concentrated insulins like U-200 or U-300 for severe insulin resistance
- Addressing contributing factors such as sleep disorders, stress management, and treating underlying infections or hormonal imbalances is essential
- Regular follow-up every 3-6 months with adjustment of the treatment plan based on glycemic response helps manage this progressive condition effectively, as emphasized in the 2016 American Diabetes Association standards of medical care in diabetes 1.
From the FDA Drug Label
Clinical studies demonstrate that ACTOS improves insulin sensitivity in insulin-resistant patients. In patients with type 2 diabetes, the decreased insulin resistance produced by ACTOS results in lower plasma glucose concentrations, lower plasma insulin levels, and lower HbA1c values.
The causes of worsening insulin resistance are not directly addressed in the provided drug labels. The workup for worsening insulin resistance is not mentioned. For treatment, pioglitazone (ACTOS) can be used to improve insulin sensitivity in insulin-resistant patients, which may help reduce the need for more insulin treatment.
- The recommended initial dose of ACTOS is 15 mg or 30 mg once daily.
- The dose can be increased in increments up to 45 mg once daily.
- Combination therapy with sulfonylurea, metformin, or insulin can be considered for patients not responding adequately to monotherapy 2, 2.
From the Research
Causes of Worsening Insulin Resistance
- Illness, medications, the endocrine and inflammatory response to stress, and pain can contribute to insulin resistance and further aggravate preexisting insulin resistance caused by obesity 3
- Weight gain caused by insulin treatment can also contribute to worsening insulin resistance 4
- Long diabetes duration, obesity, insulin resistance, and female sex can indicate a need for further treatment intensification 5
Workup for Worsening Insulin Resistance
- Evaluate for potential causes of insulin resistance from technical factors that cause "pseudo-insulin resistance" as well as other modifiable factors, such as electrolyte disorders, parenteral and enteral nutrition, or other medications 3
- Assess plasma glucose profiles to determine the need for treatment intensification 5
Treatment of Worsening Insulin Resistance
- Pharmacological options for managing patients with severe insulin resistance include the use of U-500 insulin and newer agents in combination with insulin 4
- Metformin and pioglitazone can be used to effectively treat insulin resistance, with distinct molecular mechanisms of action and differing effects on metabolic dysfunction 6
- GLP-1 receptor agonists can be used as an add-on agent to existing metformin monotherapy, or in combination with other oral glucose-lowering agents or basal insulin, to improve glycemic control and reduce metabolic risk 7
- A stepwise approach to evaluate and treat severe insulin resistance in the hospitalized patient can help achieve glucose goals in a timely fashion 3