Does medroxyprogesterone interfere with Mounjaro (tirzepatide) in an adult patient with type 2 diabetes?

No Clinically Significant Drug Interaction Between Medroxyprogesterone and Mounjaro

Medroxyprogesterone does not interfere with Mounjaro (tirzepatide) through direct pharmacologic mechanisms, and no evidence suggests these medications cannot be used together in adults with type 2 diabetes. However, one important clinical consideration exists: in breastfeeding women with prior gestational diabetes, progestin-only contraceptives including depot medroxyprogesterone acetate have been associated with increased diabetes risk 1.

Key Clinical Considerations

No Direct Drug-Drug Interaction

• Tirzepatide functions as a dual GIP/GLP-1 receptor agonist that improves glycemic control through glucose-dependent mechanisms 2, 3
• Medroxyprogesterone is a progestin used for contraception and hormone therapy with no known interference with incretin-based therapies
• No evidence from the SURPASS clinical trial program (which enrolled over 2,500 participants) identified hormonal contraceptives as problematic concurrent medications 4, 5, 6

Special Population Warning: Breastfeeding Women with Diabetes History

• In Latino breastfeeding women with prior gestational diabetes, depot medroxyprogesterone acetate (150 mg every 3 months) was associated with a two- to threefold increase in diabetes risk 1
• This finding suggests progestin-only agents should be used with caution specifically during breastfeeding in women with diabetes risk factors 1
• This concern relates to diabetes development risk, not to interference with existing diabetes medications like tirzepatide 1

Clinical Algorithm for Concurrent Use

For Non-Breastfeeding Adults with Type 2 Diabetes

• Prescribe medroxyprogesterone and tirzepatide together without dose adjustments 1
• Monitor glycemic control through HbA1c targeting 7-8% as standard 7, 8
• No additional safety monitoring beyond routine diabetes care is required 4, 5

For Breastfeeding Women with Prior Gestational Diabetes

• Consider non-hormonal contraceptive methods first 1
• If hormonal contraception is necessary, combination oral contraceptives (lowest doses, started 6-8 weeks postpartum) may be preferable to progestin-only agents 1
• If depot medroxyprogesterone is chosen despite increased diabetes risk, perform oral glucose tolerance testing at 1 year and every 3 years minimum 1
• Tirzepatide remains effective for glycemic management regardless of contraceptive choice 4, 6

Tirzepatide Efficacy Remains Unchanged

• Tirzepatide produces HbA1c reductions of 1.87-2.59% and weight loss of 6.2-12.9 kg across diverse populations 3
• No hormonal medications were identified as reducing tirzepatide's glucose-lowering or weight loss effects in clinical trials 4, 5, 6
• The medication's safety profile (primarily gastrointestinal side effects) is unaffected by concurrent progestin use 4, 5

Common Pitfall to Avoid

• Do not confuse the epidemiologic association between depot medroxyprogesterone and increased diabetes development risk in a specific population (breastfeeding women with prior GDM) with direct pharmacologic interference with tirzepatide's mechanism of action 1
• These are separate clinical concerns: one relates to diabetes prevention, the other to diabetes treatment efficacy 1, 7