How to manage a patient with diabetes who declines insulin therapy?

Managing Diabetes When a Patient Declines Insulin

If a patient declines insulin therapy, intensify non-insulin agents with triple combination therapy using metformin plus two additional agents with complementary mechanisms (such as a GLP-1 receptor agonist and SGLT2 inhibitor), while simultaneously providing education and counseling to overcome insulin reluctance, recognizing that most patients can be persuaded to accept insulin with proper encouragement. 1

Initial Response to Insulin Refusal

Patient Education and Counseling

• Most patients express reluctance to beginning injectable therapy, but if the practitioner feels that such a transition is important, encouragement and education can usually overcome such reticence. 1
• Address specific fears about insulin including concerns about hypoglycemia, weight gain, injection pain, and perceived disease severity. 1
• Emphasize that insulin refusal in the setting of severe hyperglycemia (HbA1c ≥10-12%) or catabolic features poses potentially life-threatening risks. 2

Assess the Clinical Urgency

• If the patient presents with severe hyperglycemia (glucose ≥300-350 mg/dL or HbA1c ≥10-12%) with catabolic features (weight loss, ketosis), insulin therapy is mandatory and refusal should trigger intensive counseling about life-threatening risks. 1
• For type 1 diabetes specifically, there are no alternatives to insulin replacement, and absolute refusal requires psychological support to address barriers. 2
• In less severe hyperglycemia (HbA1c 8-10%), there is a narrow window to attempt intensive non-insulin therapy while continuing insulin education. 1

Intensifying Non-Insulin Therapy

Triple Combination Approach

• Add a third non-insulin agent to the existing regimen, selecting agents with complementary mechanisms of action. 1
• The most effective combinations typically include metformin (if tolerated) plus a GLP-1 receptor agonist plus an SGLT2 inhibitor, as these provide substantial HbA1c reduction through different pathways. 3
• Alternative triple combinations can include metformin, a DPP-4 inhibitor, and a sulfonylurea, though this carries higher hypoglycemia risk. 1

Monitoring and Reassessment

• Monitor the patient closely and promptly reconsider the approach if unsuccessful—many months of uncontrolled hyperglycemia should specifically be avoided. 1
• Reassess HbA1c every 3 months; if HbA1c remains ≥8.5% after 3 months of triple therapy, insulin becomes essential. 1
• The rationale, benefits, and side effects of each new medication should be discussed with the patient. 1

Critical Pitfalls to Avoid

Do Not Delay Indefinitely

• At HbA1c levels ≥8.5%, it becomes unlikely that additional non-insulin agents will provide sufficient benefit, and insulin should be strongly favored. 1
• Prolonged uncontrolled hyperglycemia increases the risk of long-term complications and should be avoided even if it means more intensive counseling about insulin. 1

Recognize When Non-Insulin Options Are Exhausted

• Increasing the number of drugs heightens the potential for side effects, drug-drug interactions, raises costs, and negatively impacts patient adherence. 1
• Triple non-insulin therapy is a temporizing measure, not a long-term solution for patients who truly need insulin. 1

Transitioning to Insulin When Ready

Starting Insulin Therapy

• When the patient agrees to insulin, begin with a single injection of basal insulin at a low dose (0.1-0.2 units/kg/day), which is the most convenient strategy. 1
• Continue metformin and potentially one other non-insulin agent (such as a GLP-1 receptor agonist or SGLT2 inhibitor) to reduce insulin requirements and minimize weight gain. 1, 4
• Teach patients to self-titrate their insulin dose, adding 1-2 units once or twice weekly if fasting glucose levels remain above target. 1

Special Considerations for Type 1 Diabetes

• For type 1 diabetes, insulin is absolutely mandatory and cannot be replaced by any oral or non-insulin injectable agent. 2
• If a type 1 diabetes patient refuses insulin, offer psychological support to address barriers, as this refusal poses immediate life-threatening risk of diabetic ketoacidosis. 2

Alternative Strategies for Severe Cases

GLP-1 Receptor Agonists as Bridge Therapy

• GLP-1 receptor agonists can provide substantial HbA1c reduction (1-1.5%) and may serve as a bridge while continuing insulin education. 3
• These agents reduce hypoglycemia risk compared to sulfonylureas and may be better tolerated by insulin-reluctant patients. 3

Fixed-Ratio Combinations

• Once insulin is accepted, fixed-ratio combinations of basal insulin with GLP-1 receptor agonists (such as glargine/lixisenatide or degludec/liraglutide) can reduce the multiple drug adherence burden while improving glycemic control. 3