What medications should be initiated when starting a Glucagon-Like Peptide (GLP) medication like Ozempic (semaglutide) or a Glucagon-Like Peptide/Glucose-Dependent Insulinotropic Polypeptide (GLP/GIP) medication like Mounjaro (tirzepatide)?

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Last updated: May 6, 2025 • View editorial policy

From the Guidelines

When starting GLP-1 medications like Ozempic or GLP-1/GIP medications like Mounjaro, it is recommended to initiate metformin concurrently, if not already on it, due to its high glucose-lowering efficacy, neutral effect on weight, and potential benefit on major adverse cardiovascular events (MACE) as stated in the 2025 standards of care in diabetes 1. To minimize potential gastrointestinal side effects associated with GLP-1 and GLP-1/GIP medications, consider adding anti-nausea medications like ondansetron 4mg as needed up to three times daily. For constipation, starting a stool softener such as docusate sodium 100mg once or twice daily or an osmotic laxative like MiraLAX 17g daily can be beneficial. Key considerations for these medications include:

  • Monitoring for potential vitamin B12 deficiency with metformin use, as it may cause deficiency over time 1.
  • Being aware of the risk of diabetic ketoacidosis (DKA) with SGLT2 inhibitors, although this is rare in type 2 diabetes, and taking steps to mitigate this risk such as sick-day planning and discontinuing the medication before scheduled surgery or during critical illness 1.
  • Understanding the potential benefits of GLP-1 RAs on cardiovascular outcomes and renal endpoints, which can guide the decision to use these medications in appropriate patients 1. Adequate hydration, aiming for at least 2-3 liters of water daily, and a daily multivitamin are also recommended to minimize side effects and ensure adequate nutrient intake. Starting these supportive treatments proactively can improve medication adherence and overall treatment success. It's crucial to follow the dosing considerations for each medication, especially in patients with kidney impairment, and to be mindful of the potential for drug interactions and the need for dose adjustments based on kidney function 1.

From the Research

Medications to Start with GLP or GLP/GIP Medications

When starting a GLP medication like Ozempic or a GLP/GIP medication like Mounjaro, the following medications should be considered:

  • Metformin: often prescribed as a first-line treatment for type 2 diabetes, it can be used in conjunction with GLP or GLP/GIP medications 2, 3
  • Statins: to manage cholesterol levels and reduce the risk of cardiovascular disease, which is often a comorbidity with type 2 diabetes 4
  • Antihypertensives: to manage blood pressure and reduce the risk of cardiovascular disease 4
  • Aspirin: to reduce the risk of cardiovascular disease, although this should be individualized based on patient risk factors 4

Considerations for Medication Selection

When selecting medications to start with GLP or GLP/GIP medications, the following factors should be considered:

  • Patient's medical history and comorbidities
  • Current medications and potential interactions
  • Patient's kidney function and potential need for dose adjustments
  • Patient's liver function and potential need for monitoring

Potential Benefits of Combination Therapy

Combination therapy with GLP or GLP/GIP medications and other medications may have several benefits, including:

  • Improved glycemic control
  • Weight loss
  • Improved lipid metabolism
  • Reduced blood pressure
  • Reduced risk of cardiovascular disease 2, 3, 4

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.