What medications can be added to a type 2 diabetes mellitus (T2DM) patient on Jardiance (Empagliflozin) and insulin with inadequate glycemic control?

From the Guidelines

For a type 2 diabetic patient on Jardiance (empagliflozin) and insulin with inadequate glycemic control, adding a GLP-1 receptor agonist such as semaglutide (Ozempic, weekly injection starting at 0.25mg and titrating to 0.5-1mg) or dulaglutide (Trulicity, weekly injection starting at 0.75mg and increasing to 1.5mg) would be an excellent option to further improve glycemic control, as recommended by the 2024 guidelines 1.

Key Considerations

• The choice of medication should consider factors like weight concerns, injection preference, cost, and comorbidities.
• GLP-1 receptor agonists can effectively lower A1c by 1-1.5% while promoting weight loss and having cardiovascular benefits, as supported by studies such as the 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD 1.
• Other options like DPP-4 inhibitors (e.g., sitagliptin, 100mg daily) or pioglitazone (15-30mg daily) may also be considered, but GLP-1 receptor agonists are generally more potent and have additional cardiovascular benefits.
• The 2020 standards of medical care in diabetes-2020 also support the use of GLP-1 receptor agonists and SGLT2 inhibitors in patients with type 2 diabetes and established or high risk of ASCVD, CKD, or HF 1.

Mechanism of Action

• GLP-1 receptor agonists work by enhancing glucose-dependent insulin secretion, suppressing glucagon secretion, and slowing gastric emptying.
• SGLT2 inhibitors, like Jardiance, work by reducing glucose reabsorption in the kidneys, increasing glucose excretion in the urine, and reducing glucose production in the liver.
• The combination of these mechanisms can provide a synergistic effect, improving glycemic control and reducing cardiovascular risk.

Clinical Evidence

• Studies have shown that GLP-1 receptor agonists can reduce the risk of major adverse cardiovascular events (MACE) and improve kidney function, as seen in the 2024 guidelines 1 and the 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD 1.
• The 2020 standards of medical care in diabetes-2020 also provide evidence for the use of GLP-1 receptor agonists and SGLT2 inhibitors in patients with type 2 diabetes and established or high risk of ASCVD, CKD, or HF 1.

From the FDA Drug Label

Add-On Combination Therapy with Pioglitazone with or without Metformin A total of 498 patients with type 2 diabetes mellitus participated in a double-blind, placebo-controlled trial to evaluate the efficacy of JARDIANCE in combination with pioglitazone, with or without metformin Add-On Combination with Insulin with or without Metformin and/or Sulfonylureas A total of 494 patients with type 2 diabetes mellitus inadequately controlled on insulin, or insulin in combination with oral drugs participated in a double-blind, placebo-controlled trial to evaluate the efficacy of JARDIANCE as add-on therapy to insulin over 78 weeks.

The medications that can be added to a type 2 diabetes mellitus (T2DM) patient on Jardiance (Empagliflozin) and insulin with inadequate glycemic control are:

• Pioglitazone: with or without metformin
• Metformin: with or without sulfonylureas
• Sulfonylureas: with or without metformin

2

From the Research

Medication Options for T2DM Patients on Jardiance (Empagliflozin) and Insulin

• For T2DM patients on Jardiance (Empagliflozin) and insulin with inadequate glycemic control, several medication options can be considered:
  • Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as exenatide, liraglutide, or dulaglutide, which have been shown to be effective in reducing HbA1c levels and can be used in combination with insulin 3
  • Thiazolidinediones such as pioglitazone, which can be used in combination with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, to improve glycemic control 4
  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors like empagliflozin, which can be used as monotherapy or in combination with other antidiabetic agents, including insulin, to improve glycemic control 5
  • Fixed-ratio combination therapies that combine basal insulin with a GLP-1 RA, such as iGlarLixi or IDegLira, which have been shown to be effective and well-tolerated in patients with T2D 6

Considerations for Medication Selection

• When selecting a medication to add to a T2DM patient's regimen, considerations should include:
  • The patient's current level of glycemic control and the desired level of control
  • The presence of any comorbid conditions, such as cardiovascular disease or kidney disease
  • The potential for adverse effects, such as hypoglycemia or weight gain
  • The patient's individual preferences and needs, including the convenience of once-daily dosing and the potential for weight loss 3, 7, 5, 6