Should a thin patient on multiple medications with short-acting subcutaneous (sc) insulin who is still not controlled be considered for a Glucagon-like peptide-1 (GLP-1) receptor agonist?

GLP-1 Receptor Agonists for Thin Patients on Multiple Drugs with SC Insulin

GLP-1 receptor agonists should be considered for thin patients on multiple medications with short-acting subcutaneous insulin who are still not achieving glycemic control, as they offer effective glucose-lowering benefits without weight gain and have minimal risk of hypoglycemia when used appropriately. 1

Benefits of Adding GLP-1 Receptor Agonists to Insulin Therapy

• GLP-1 receptor agonists effectively lower glucose by stimulating insulin secretion and reducing glucagon secretion in a glucose-dependent manner, delaying gastric emptying, and reducing food intake via central appetite suppression 1
• When added to basal insulin, GLP-1 receptor agonists can reduce HbA1c and body weight, unlike the weight gain typically seen with intensification using prandial insulin 1, 2
• GLP-1 receptor agonists have high glucose-lowering efficacy with minimal risk of hypoglycemia when used alone, though they may increase hypoglycemic potential when combined with insulin or sulfonylureas 1, 3
• The combination of basal insulin plus a GLP-1 receptor agonist is associated with weight loss and less hypoglycemia compared to regimens using insulin alone 1

Clinical Considerations for Thin Patients

• For thin patients who may not need weight loss benefits, the insulin-sparing effect of GLP-1 receptor agonists remains valuable, potentially reducing insulin requirements while maintaining or improving glycemic control 2, 4
• When adding a GLP-1 receptor agonist to existing insulin therapy, the dose of basal insulin should be decreased by approximately 20% in patients with an HbA1c ≤8% to reduce the risk of hypoglycemia 2
• In patients who have failed to achieve glycemic targets on basal insulin in combination with oral medications, GLP-1 receptor agonists are a preferred option before advancing to multiple daily insulin injections 1

Medication Selection and Dosing

• Several GLP-1 receptor agonists are available with different dosing frequencies: twice daily (exenatide), once daily (liraglutide and lixisenatide), or once weekly (semaglutide, dulaglutide, exenatide extended-release) 1, 5
• Evidence suggests that the glucose-lowering effect may be greatest for semaglutide once weekly, followed by dulaglutide and liraglutide, then exenatide once weekly, and finally exenatide twice daily and lixisenatide 1
• Start with a low dose and titrate slowly to minimize gastrointestinal side effects, which are the most common adverse events 1, 5

Potential Adverse Effects and Monitoring

• The most common adverse effects are gastrointestinal symptoms (nausea, vomiting, diarrhea), which typically occur in the initial stage of treatment and gradually diminish over time 1, 3
• Rare but serious adverse effects include acute pancreatitis; GLP-1 receptor agonists should be used with caution in patients with a history of pancreatitis 1, 6
• Monitor for potential worsening of diabetic retinopathy, particularly in patients with pre-existing retinopathy and those experiencing rapid improvement in glycemic control 6
• There have been reports of acute kidney injury with GLP-1 receptor agonists, primarily through hemodynamic derangement due to gastrointestinal symptoms; monitor renal function when initiating or escalating doses 6, 3

Cardiovascular Benefits

• Several GLP-1 receptor agonists (liraglutide, semaglutide, lixisenatide, exenatide) have demonstrated cardiovascular protective effects in patients with type 2 diabetes with a history of cardiovascular disease or cardiovascular risk factors 1
• For patients with established atherosclerotic cardiovascular disease, GLP-1 receptor agonists are particularly recommended due to their proven cardiovascular benefits 1

Implementation Strategy

1. Assess the patient's current insulin regimen and glycemic control
2. If adding GLP-1 receptor agonist to existing insulin therapy:
   • Reduce basal insulin dose by approximately 20% if HbA1c ≤8% 2
   • Start with the lowest dose of the selected GLP-1 receptor agonist and titrate slowly 1
   • Monitor for hypoglycemia and adjust insulin doses accordingly 1, 2
3. If transitioning from multiple daily insulin injections to basal insulin plus GLP-1 receptor agonist:
   • Maintain basal insulin but reduce dose by 20% 2
   • Discontinue prandial insulin and initiate GLP-1 receptor agonist at the lowest dose 1
   • Titrate GLP-1 receptor agonist as tolerated while monitoring glycemic control 5

Special Considerations for Thin Patients

• While most studies focus on overweight/obese patients with type 2 diabetes, the insulin-sparing and glucose-lowering effects of GLP-1 receptor agonists make them valuable even for thin patients 2, 4
• The combination may be particularly beneficial for thin patients who are insulin-deficient but still have some beta-cell function, as GLP-1 receptor agonists enhance glucose-dependent insulin secretion 1, 5
• For patients with significant insulin deficiency, careful monitoring is needed as GLP-1 receptor agonists require some residual beta-cell function for optimal efficacy 1