Is the combination of Mounjaro (tirzepatide), Glipizide (Glibenclamide), and Metformin effective for managing diabetes?

From the Guidelines

The combination of Mounjaro (tirzepatide), glipizide, and metformin can be effective for managing type 2 diabetes, but this specific three-drug combination should only be used under careful medical supervision. Metformin is typically the first-line medication that works by reducing glucose production in the liver and improving insulin sensitivity, as recommended by the latest guidelines 1. Glipizide is a sulfonylurea that stimulates insulin release from the pancreas. Mounjaro (tirzepatide) is a newer GLP-1/GIP dual receptor agonist that slows digestion, increases insulin secretion, and reduces appetite.

There are potential concerns with this specific combination, particularly the risk of hypoglycemia (low blood sugar) when Mounjaro is used alongside a sulfonylurea like glipizide. Your doctor may need to reduce your glipizide dose when adding Mounjaro, as suggested by the American College of Physicians 1. Additionally, this combination may cause overlapping side effects like gastrointestinal issues. The appropriateness of this regimen depends on your specific diabetes control needs, kidney function, weight management goals, and other health factors.

Some studies have raised concerns about the safety of combining metformin with sulfonylureas, citing an increased risk of diabetes-related deaths and all-cause mortality 1. However, the most recent and highest-quality study recommends metformin as the first-line treatment for type 2 diabetes, with the option to add other agents, including sulfonylureas, if necessary 1.

Key considerations for this combination include:

• Regular blood sugar monitoring to minimize the risk of hypoglycemia
• Careful dose adjustment of glipizide when adding Mounjaro
• Monitoring for overlapping side effects, such as gastrointestinal issues
• Individualized assessment of the patient's diabetes control needs, kidney function, and weight management goals.

Overall, the decision to use this combination should be made on a case-by-case basis, taking into account the latest evidence and the patient's specific needs and health status, as recommended by the latest guidelines 1.

From the FDA Drug Label

In adult patients with type 2 diabetes mellitus, treatment with MOUNJARO produced a statistically significant reduction from baseline in HbA1c compared to placebo The effectiveness of MOUNJARO was not impacted by age, gender, race, ethnicity, region, or by baseline BMI, HbA1c, diabetes duration, or renal function. 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.

The combination of Mounjaro, glipizide, and metformin for diabetes is not directly addressed in the provided drug labels 2 and 2.

• Mounjaro is shown to be effective in reducing HbA1c when used as monotherapy or in combination with metformin.
• Glipizide, a sulfonylurea, is mentioned as a potential add-on therapy, but there is no direct information on its combination with Mounjaro and metformin.
• Metformin is a commonly used medication for type 2 diabetes, and Mounjaro has been studied in combination with metformin, but not specifically with glipizide. Therefore, no conclusion can be drawn about the safety and efficacy of this specific combination.

From the Research

Combination of Mounjaro, Glipizide, and Metformin for Diabetes

• The combination of Mounjaro (tirzepatide), glipizide, and metformin for the treatment of diabetes has not been directly studied in the provided evidence 3, 4, 5, 6, 7.
• However, the individual components of this combination have been studied:
  • Mounjaro (tirzepatide) has been shown to be effective in improving glycemic control and reducing body weight in patients with type 2 diabetes, with a similar safety profile to GLP-1 receptor agonists 3, 4, 5, 6, 7.
  • Metformin is a commonly used medication for the treatment of type 2 diabetes, and has been shown to be effective in improving glycemic control and reducing the risk of cardiovascular events 5.
  • Glipizide is a sulfonylurea that stimulates insulin secretion, but its use in combination with Mounjaro and metformin has not been specifically studied in the provided evidence.
• The use of Mounjaro in combination with other glucose-lowering medications, including metformin, has been studied, and has been shown to be effective in improving glycemic control and reducing body weight 5, 6, 7.
• However, the safety and efficacy of the specific combination of Mounjaro, glipizide, and metformin has not been established, and would require further study to determine its potential benefits and risks 3, 4, 5, 6, 7.

Efficacy of Mounjaro

• Mounjaro (tirzepatide) has been shown to be effective in improving glycemic control and reducing body weight in patients with type 2 diabetes, with a similar safety profile to GLP-1 receptor agonists 3, 4, 5, 6, 7.
• The efficacy of Mounjaro has been demonstrated in several clinical trials, including the SURPASS-3 trial, which compared Mounjaro to insulin degludec in patients with type 2 diabetes inadequately controlled by metformin with or without SGLT2 inhibitors 5.
• Mounjaro has also been compared to semaglutide, a selective GLP-1 receptor agonist, in the SURPASS-2 trial, and was shown to be noninferior and superior to semaglutide in terms of glycemic control and weight reduction 6.

Safety of Mounjaro

• The safety profile of Mounjaro (tirzepatide) has been evaluated in several clinical trials, and has been shown to be similar to that of GLP-1 receptor agonists 3, 4, 5, 6, 7.
• The most common adverse events associated with Mounjaro are gastrointestinal, including nausea, diarrhea, and vomiting, which are typically mild to moderate in severity 5, 6, 7.
• Mounjaro has been shown to have a lower risk of hypoglycemia compared to basal insulin regimens, and a similar risk of hypoglycemia compared to GLP-1 receptor agonists 5, 6, 7.