What medications should be dose-adjusted when starting Mounjaro (tirzepatide) in a patient with impaired renal function and a history of pancreatic disease, taking insulin, GLP-1 receptor agonists, DPP-4 inhibitors, ACE inhibitors, or ARBs?

Medication Dose Adjustments When Initiating Mounjaro (Tirzepatide)

Insulin and Insulin Secretagogues: Reduce Doses to Prevent Hypoglycemia

When starting Mounjaro, reduce the dose of concomitantly administered insulin secretagogues (e.g., sulfonylureas) or insulin to minimize hypoglycemia risk. 1

Insulin Dose Reduction Strategy

• Reduce basal insulin dose by 20-30% when adding Mounjaro, particularly if baseline HbA1c is near target 1
• Monitor blood glucose closely during the first 2-4 weeks after initiation 1
• Further insulin dose reductions may be needed as Mounjaro is titrated upward 1

Sulfonylurea Dose Reduction

• Consider reducing sulfonylurea dose by 50% or discontinuing entirely when initiating Mounjaro 1
• The addition of GLP-1 receptor agonists (Mounjaro's class mechanism) to sulfonylurea therapy increases hypoglycemia risk by approximately 50% 2
• Given Mounjaro's potent glucose-lowering effects (HbA1c reductions of 1.62-2.06% vs placebo), sulfonylureas often become unnecessary 3

DPP-4 Inhibitors: Discontinue Before Starting Mounjaro

Discontinue DPP-4 inhibitors (sitagliptin, linagliptin, saxagliptin, alogliptin, teneligliptin) when initiating Mounjaro. 4

• GLP-1 receptor agonists should not be used in combination with DPP-4 inhibitors due to overlapping mechanisms of action 4
• Both drug classes work through incretin pathways, making combination therapy redundant and potentially increasing adverse effects without additional glycemic benefit 2
• No dose tapering is required; DPP-4 inhibitors can be stopped abruptly when starting Mounjaro 4

Other GLP-1 Receptor Agonists: Discontinue

Discontinue any existing GLP-1 receptor agonist therapy (dulaglutide, semaglutide, liraglutide, exenatide) before starting Mounjaro 4

• Mounjaro is itself a dual GIP/GLP-1 receptor agonist, making combination with another GLP-1 RA unnecessary and potentially harmful 5
• No overlap or bridging therapy is needed 4

Oral Hormonal Contraceptives: Switch or Add Barrier Method

Advise patients using oral hormonal contraceptives to switch to a non-oral contraceptive method, or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation. 1

• Mounjaro delays gastric emptying, which may reduce the efficacy of oral hormonal contraceptives 1
• This delay is largest after the first dose and diminishes over time 1
• Non-oral hormonal contraceptives (patches, injections, IUDs) are not affected and do not require adjustment 1

Medications Requiring Monitoring (But Not Necessarily Dose Adjustment)

Warfarin and Narrow Therapeutic Index Drugs

• Monitor INR more frequently when initiating Mounjaro in patients on warfarin 1
• Mounjaro's delayed gastric emptying may impact absorption of oral medications with narrow therapeutic indices 1
• Monitor patients on oral medications dependent on threshold concentrations for efficacy 1

ACE Inhibitors and ARBs: Continue Without Adjustment

ACE inhibitors and ARBs do not require dose adjustment when starting Mounjaro. 4

• Continue ACE inhibitors or ARBs at the maximally tolerated dose in patients with diabetes, hypertension, and albuminuria 4
• Monitor serum creatinine and potassium within 2-4 weeks of any change, but this is standard monitoring for RAS inhibitors, not specific to Mounjaro initiation 4
• Continue ACE inhibitor or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks 4

Renal and Hepatic Impairment: No Dose Adjustment Required

No dosage adjustment of Mounjaro is recommended for patients with renal or hepatic impairment. 1, 6

• Tirzepatide pharmacokinetics remain unchanged in patients with renal impairment, including end-stage renal disease requiring dialysis 1, 6
• Monitor renal function when initiating or escalating doses in patients with renal impairment who report severe gastrointestinal reactions 1
• No change in tirzepatide pharmacokinetics was observed in patients with hepatic impairment 1

Common Pitfalls to Avoid

• Do not continue DPP-4 inhibitors "just in case" – they provide no additional benefit and increase adverse event risk 4, 2
• Do not forget to counsel about oral contraceptive efficacy – this is a critical safety issue that requires proactive management 1
• Do not delay insulin/sulfonylurea dose reduction – hypoglycemia risk is highest in the first few weeks after Mounjaro initiation 1
• Do not assume metformin needs adjustment – metformin can and should be continued at current doses when adding Mounjaro 4
• Do not reduce SGLT2 inhibitor doses – these should be continued for their cardiovascular and renal protective effects independent of glucose-lowering 4