What are the alternative diabetes management options for a patient who refuses pre-prandial insulin or bolus injections?

Alternative Diabetes Management Options for Patients Refusing Pre-Prandial Insulin

For patients who refuse pre-prandial insulin or bolus injections, premixed insulin formulations administered twice daily are the most effective alternative management strategy.

Premixed Insulin as Primary Alternative

• Premixed insulin formulations (such as 70/30 or 75/25) provide both basal and prandial coverage with fewer daily injections, making them an excellent option for patients unwilling to use pre-prandial insulin 1, 2
• Typically administered twice daily, 30 minutes before breakfast and dinner, as recommended by clinical guidelines 2
• Initial dosing should start with 10 units or 0.1-0.2 units/kg of body weight per day, divided into two equal doses 2
• Titration should be based on fasting plasma glucose targets, increasing by 2 units every 3 days if 50% of fasting glucose readings are above target 2

GLP-1 Receptor Agonists as Alternative or Add-on

• When selecting injectable therapies, GLP-1 receptor agonists (GLP-1 RAs) should be considered before insulin intensification for patients refusing multiple daily injections 1
• GLP-1 RAs can be particularly beneficial for patients who need improved postprandial glucose control but refuse mealtime insulin 1
• For patients already on basal insulin who refuse to add mealtime insulin, adding a GLP-1 RA is an effective alternative to control postprandial glucose excursions 1
• Fixed-ratio combinations of basal insulin and GLP-1 RAs (such as IDegLira or iGlarLixi) can be considered for patients already on basal insulin therapy 1

DPP-4 Inhibitors as Adjunctive Therapy

• For patients with mild-to-moderate hyperglycemia who refuse prandial insulin, adding a DPP-4 inhibitor to basal insulin can improve glycemic control 1, 3
• Linagliptin has shown efficacy when added to basal insulin therapy, reducing HbA1c by 0.6% compared to placebo 3
• DPP-4 inhibitors are particularly useful for patients with lower blood glucose concentrations (<11.1 mmol/L or <200 mg/dL) who are either insulin naïve or treated with very low doses of insulin 1

SGLT-2 Inhibitors as Adjunctive Therapy

• SGLT-2 inhibitors can be added to basal insulin therapy to improve glycemic control and potentially reduce insulin requirements 1
• These agents have the added benefit of cardiovascular and renal protection, which should be considered in treatment selection 1
• For patients with heart failure, SGLT-2 inhibitors should be particularly considered as adjunctive therapy to insulin 1

Thrice-Daily Premixed Insulin Option

• If glycemic targets are not achieved with twice-daily premixed insulin, consider advancing to three-times-daily premixed insulin 2, 4
• Thrice-daily biphasic human insulin (30/70) has shown comparable efficacy to basal-bolus regimens in some studies, with less insulin dose increment 4
• This approach can provide better postprandial coverage while still avoiding the need for separate mealtime insulin injections 4, 5

Practical Implementation Considerations

• Comprehensive diabetes education is essential, focusing on blood glucose monitoring, nutrition, and hypoglycemia recognition 1
• Self-titration algorithms based on self-monitoring of blood glucose can improve glycemic control in patients initiating insulin therapy 1
• In cases of hypoglycemia, decrease the insulin dose by 10-20% 2
• For patients on glucocorticoid therapy, higher insulin doses may be required, particularly for daytime hyperglycemia 2

Monitoring and Follow-up

• Blood glucose monitoring is integral to effective insulin therapy 6
• Fasting plasma glucose values should be used to titrate basal insulin, whereas both fasting and postprandial values should be monitored when using premixed insulin 6
• Glycemic control should be evaluated every 2 weeks and therapy adjusted as needed 2
• Target HbA1c should be individualized based on hypoglycemia risk, with less stringent goals (such as 7.5%) appropriate if there is increased risk of hypoglycemia 1

Important Cautions

• Hypoglycemia risk may be higher with premixed insulin compared to basal-only regimens, requiring careful monitoring and dose adjustment 5
• Weight gain is common with insulin therapy; consider continuing metformin to help mitigate this effect 6
• Oral medications should not be abruptly discontinued when starting insulin therapy because of the risk of rebound hyperglycemia 6
• Lipohypertrophy can distort insulin absorption; proper injection site rotation is essential 6