What medication can be added to a diabetic patient's regimen who is already on Mounjaro (tirzepatide) and long-acting insulin?

From the Guidelines

For a diabetic patient already on Mounjaro (tirzepatide) and long-acting insulin, adding a sodium-glucose cotransporter-2 (SGLT2) inhibitor like empagliflozin (Jardiance), dapagliflozin (Farxiga), or canagliflozin (Invokana) would be a beneficial addition to their regimen. These medications work through a different mechanism than both tirzepatide and insulin by preventing glucose reabsorption in the kidneys, leading to increased glucose excretion in urine. According to the KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease 1, an SGLT2i can be added to other antihyperglycemic medications for patients whose glycemic targets are not currently met or who are meeting glycemic targets but can safely attain a lower target. Typically, an SGLT2 inhibitor would be started at the standard dose (e.g., empagliflozin 10mg daily, dapagliflozin 5mg daily) and can be titrated up if needed. When adding this medication, it's essential to monitor for potential side effects, including genital mycotic infections, urinary tract infections, and volume depletion, as recommended by the 2019 Standards of Medical Care in Diabetes 1. Patients should be advised to maintain adequate hydration and proper genital hygiene. Blood glucose monitoring should be continued, and insulin doses may need adjustment as the SGLT2 inhibitor takes effect. This triple therapy approach targets multiple pathways of glucose regulation: tirzepatide affects GLP-1 and GIP receptors to improve insulin secretion and reduce glucagon, long-acting insulin provides basal insulin coverage, and SGLT2 inhibitors reduce glucose reabsorption independently of insulin action. Additionally, the 2019 Standards of Medical Care in Diabetes 1 recommend considering the early introduction of insulin and the use of SGLT2 inhibitors in patients with established atherosclerotic cardiovascular disease. It is also crucial to consider the patient's comorbidities, hypoglycemia risk, impact on weight, cost, risk for side effects, and patient preferences when choosing pharmacologic agents, as stated in the 2019 Standards of Medical Care in Diabetes 1. The KDIGO 2020 guideline 1 also suggests that for patients in whom additional glucose-lowering may increase the risk for hypoglycemia, it may be necessary to stop or reduce the dose of an antihyperglycemic drug other than metformin to facilitate the addition of an SGLT2i. However, the most recent and highest-quality study, the 2019 Standards of Medical Care in Diabetes 1, provides the most relevant guidance for this patient population. Key points to consider when adding an SGLT2 inhibitor to a patient's regimen include:

• Starting with a standard dose and titrating up as needed
• Monitoring for potential side effects, including genital mycotic infections, urinary tract infections, and volume depletion
• Advising patients to maintain adequate hydration and proper genital hygiene
• Continuing blood glucose monitoring and adjusting insulin doses as necessary
• Considering the patient's comorbidities, hypoglycemia risk, impact on weight, cost, risk for side effects, and patient preferences when choosing pharmacologic agents.

From the FDA Drug Label

1. 3 MOUNJARO Use in Combination with Metformin, Sulfonylureas, and/or SGLT2 Inhibitors in Adult Patients with Type 2 Diabetes Mellitus Add-on to metformin SURPASS-2 (NCT03987919) was a 40-week open-label trial (double-blind with respect to MOUNJARO dose assignment) that randomized 1879 adult patients with type 2 diabetes mellitus with inadequate glycemic control on stable doses of metformin alone to the addition of MOUNJARO 5 mg, MOUNJARO 10 mg, or MOUNJARO 15 mg once weekly or subcutaneous semaglutide 1 mg once weekly. Add-on to metformin with or without SGLT2 inhibitor SURPASS-3 (NCT03882970) was a 52-week open-label trial that randomized 1444 adult patients with type 2 diabetes mellitus with inadequate glycemic control on stable doses of metformin with or without SGLT2 inhibitor to the addition of MOUNJARO 5 mg, MOUNJARO 10 mg, MOUNJARO 15 mg once weekly, or insulin degludec 100 units/mL once daily Add-on to 1-3 oral anti-hyperglycemic agents (metformin, sulfonylurea or SGLT-2 inhibitor) SURPASS-4 (NCT03730662) was a 104-week open-label trial (52-week primary endpoint) that randomized 2002 adult patients with type 2 diabetes mellitus with increased cardiovascular risk to MOUNJARO 5 mg, MOUNJARO 10 mg, MOUNJARO 15 mg once weekly, or insulin glargine 100 units/mL once daily (1:1:1:3 ratio) on a background of metformin (95%) and/or sulfonylureas (54%) and/or SGLT2 inhibitors (25%).

Medications that can be added to a diabetic patient's regimen who is already on Mounjaro (tirzepatide) and long-acting insulin:

• Metformin: can be added as it was used in combination with Mounjaro in the SURPASS-2 and SURPASS-3 trials 2
• Sulfonylureas: can be added as they were used in combination with Mounjaro in the SURPASS-4 trial 2
• SGLT2 inhibitors: can be added as they were used in combination with Mounjaro in the SURPASS-3 and SURPASS-4 trials 2

From the Research

Medication Options for Diabetic Patients on Mounjaro and Long-Acting Insulin

• The following medications can be considered as add-ons to Mounjaro (tirzepatide) and long-acting insulin for diabetic patients:
  • SGLT2 inhibitors, such as empagliflozin, canagliflozin, dapagliflozin, or remogliflozin, which have been shown to improve glycemic control and reduce body weight in patients with type 2 diabetes 3, 4, 5
  • These medications work by inhibiting the reabsorption of glucose in the kidneys, leading to increased glucose excretion in the urine and improved blood glucose control
  • SGLT2 inhibitors have been found to be effective in reducing HbA1c levels, fasting blood sugar, and post-prandial blood sugar, as well as body weight and blood pressure 5

Considerations for Adding Medications to Mounjaro and Long-Acting Insulin

• When adding SGLT2 inhibitors to Mounjaro and long-acting insulin, patients should be monitored for potential side effects, such as:
  • Urinary tract infections and genital mycotic infections, which are common side effects of SGLT2 inhibitors 3, 4, 5
  • Hypoglycemia, although the risk is lower with SGLT2 inhibitors compared to insulin 6
  • Other potential side effects, such as nausea, diarrhea, and vomiting, which are more common with tirzepatide than with insulin 6

Evidence for Medication Efficacy and Safety

• Studies have demonstrated the efficacy and safety of SGLT2 inhibitors in patients with type 2 diabetes, including those on basal insulin therapy 3, 4, 5
• The SURPASS-4 trial found that tirzepatide was effective in reducing HbA1c levels and had a lower incidence of hypoglycemia compared to insulin glargine 6
• Overall, the addition of SGLT2 inhibitors to Mounjaro and long-acting insulin may be a useful treatment option for patients with type 2 diabetes who require additional glycemic control without weight gain 3, 4, 5