What are the next steps for a patient with type 2 diabetes (T2D) who remains uncontrolled on a combination of Diamicron (gliclazide), Jardiance (empagliflozin), and Janumet (sitagliptin/metformin)?

Next Steps for Uncontrolled Type 2 Diabetes on Triple Therapy

For patients with type 2 diabetes who remain uncontrolled on a combination of gliclazide (Diamicron), empagliflozin (Jardiance), and sitagliptin/metformin (Janumet), insulin therapy should be initiated as soon as possible, ideally within 3 months of recognition of treatment failure. 1

Current Treatment Assessment

• The patient is already on a comprehensive regimen including:

  • Sulfonylurea (gliclazide) - insulin secretagogue
  • SGLT2 inhibitor (empagliflozin) - promotes urinary glucose excretion
  • DPP-4 inhibitor (sitagliptin) - enhances incretin effect
  • Metformin - reduces hepatic glucose production 1

• Despite this triple therapy approach targeting multiple pathways, glycemic control remains inadequate, indicating progressive beta-cell dysfunction requiring intensification 1

Recommended Next Steps

First-Line Option: Add Insulin Therapy

• Patients with T2DM who are not achieving glycemic goals with oral hypoglycemic agents should initiate insulin therapy as soon as possible 1

• Initial insulin treatment options:

  • Start with basal insulin (intermediate-acting human insulin or long-acting insulin analog) once daily 1
  • Consider starting with 10 units or 0.1-0.2 units/kg/day, titrating by 2-4 units every 3-7 days based on fasting glucose levels 1

• If basal insulin alone is insufficient:

  • Progress to basal-plus regimen (adding prandial insulin before largest meal)
  • Consider advancing to multiple daily injections (basal-bolus) if needed 1

Alternative Option: GLP-1 Receptor Agonist

• Before initiating insulin, consider adding a GLP-1 receptor agonist (such as liraglutide, semaglutide, or dulaglutide) 1

• Benefits of GLP-1 RA before insulin:

  • Greater efficacy and durability of treatment effect 1
  • Lower risk of hypoglycemia compared to insulin 1
  • Weight loss rather than weight gain 1
  • Cardiovascular protective effects in patients with established cardiovascular disease 1

• If insulin is eventually needed, combining it with a GLP-1 receptor agonist is recommended for greater efficacy 1

Special Considerations

• Evaluate for overbasalization if using basal insulin (signs include doses >0.5 IU/kg/day, high bedtime-morning glucose differential, hypoglycemia) 1

• Consider discontinuing sulfonylurea (gliclazide) when initiating insulin therapy to reduce hypoglycemia risk 1

• Maintain SGLT2 inhibitor (empagliflozin) even when initiating insulin for ongoing glycemic, cardiovascular, and renal benefits 1

• Monitor for potential adverse effects:

  • Hypoglycemia (especially with insulin and sulfonylurea combination) 1
  • Urinary tract infections (with SGLT2 inhibitor) 1
  • Gastrointestinal symptoms (with GLP-1 RA) 1

Follow-up Recommendations

• Reevaluate medication regimen every 3-6 months and adjust as needed 1

• Monitor HbA1c, fasting and postprandial glucose levels, weight, and blood pressure 1

• Assess for treatment adherence and barriers to glycemic control 1

• Continue to emphasize lifestyle modifications (diet, physical activity) as an underlying theme throughout management 1