Should I stop oral hypoglycemic agents (OHAs) when starting insulin in a patient with uncontrolled diabetes?

Continuing Oral Hypoglycemic Agents When Starting Insulin Therapy

When starting insulin therapy in a patient with uncontrolled diabetes on oral hypoglycemic agents (OHAs), you should continue metformin and other beneficial OHAs rather than stopping them completely, while reassessing the need for sulfonylureas and meglitinides due to hypoglycemia risk. 1

Evidence-Based Approach to OHAs When Starting Insulin

Continue Metformin

• Metformin should be maintained when initiating insulin therapy due to its complementary mechanism of action and beneficial effects on glycemic control and cardiovascular outcomes 1, 2
• The combination of insulin plus metformin is particularly effective for lowering glycemia while limiting weight gain 1
• Studies show that approximately 80% of patients continue metformin after insulin initiation, consistent with current guidelines 2

Reassess Other OHAs

• When starting insulin, reassess the need for and/or dose of glucose-lowering agents with higher hypoglycemia risk (specifically sulfonylureas and meglitinides) 1
• Sulfonylureas, DPP-4 inhibitors, and GLP-1 receptor agonists are typically discontinued once more complex insulin regimens beyond basal insulin are used 1
• For patients on GLP-1 receptor agonists, these should generally not be discontinued when initiating basal insulin due to their complementary effects 1

Consider Medication Benefits Beyond Glycemic Control

• SGLT2 inhibitors may be continued for their cardiorenal benefits even when starting insulin, especially in patients with heart failure or chronic kidney disease 1
• When initiating combination injectable therapy, metformin should be maintained while other oral agents may be discontinued on an individual basis to avoid unnecessarily complex regimens 1

Practical Implementation

Initial Insulin Regimen

• Start with basal insulin while continuing metformin and reassessing other OHAs 1
• Typical starting dose is 10 units per day or 0.1-0.2 units/kg/day, depending on the degree of hyperglycemia 1
• Monitor for signs of overbasalization during insulin therapy (basal dose exceeding 0.5 units/kg/day, significant glucose differentials, hypoglycemia) 1

Medication Adjustments

• When starting insulin, reduce or discontinue sulfonylureas and meglitinides to minimize hypoglycemia risk 1
• If A1C is <8% when starting mealtime bolus insulin, consider decreasing the basal insulin dose 1
• If using GLP-1 RA with insulin, insulin dosing should be reassessed upon addition or dose escalation of the GLP-1 RA 1

Special Circumstances

• In severely uncontrolled diabetes (fasting glucose >250 mg/dl, random glucose consistently >300 mg/dl, A1C >10%, ketonuria, or symptoms of polyuria, polydipsia, and weight loss), insulin therapy with lifestyle intervention is the treatment of choice 1
• After symptoms are relieved and glucose levels decreased in these severe cases, oral agents can often be added and it may be possible to withdraw insulin if preferred 1

Common Pitfalls and Caveats

• Failure to continue metformin when starting insulin therapy, which eliminates the synergistic benefits of combination therapy 1, 2
• Continuing sulfonylureas without dose adjustment when starting insulin, which increases hypoglycemia risk 1
• Creating unnecessarily complex medication regimens by adding insulin to multiple OHAs without reassessing the need for each agent 1
• Delaying insulin therapy due to fear of hypoglycemia or patient reluctance, which can prolong poor glycemic control 3

By following these evidence-based recommendations, you can optimize the transition to insulin therapy while maintaining the benefits of appropriate oral agents, ultimately improving glycemic control and reducing the risk of diabetes-related complications.