Do Not Use Mounjaro and Trulicity Together
You should not use Mounjaro (tirzepatide) and Trulicity (dulaglutide) together—both are incretin-based therapies that work through overlapping mechanisms, and combining them provides no additional benefit while increasing the risk of adverse effects, particularly gastrointestinal symptoms.
Why This Combination Makes No Sense
Overlapping Mechanisms of Action
Both drugs activate GLP-1 receptors: Trulicity (dulaglutide) is a pure GLP-1 receptor agonist, while Mounjaro (tirzepatide) is a dual GIP/GLP-1 receptor agonist that also activates GLP-1 receptors 1, 2.
Tirzepatide already provides superior efficacy: In head-to-head trials, tirzepatide demonstrated significantly greater HbA1c reduction (1.1-1.5% more) and weight loss (5.3-10.2 kg more) compared to dulaglutide across all dose comparisons 3, 4.
No rationale for dual GLP-1 activation: There is no evidence or biological rationale supporting the combination of two medications that both activate the same GLP-1 receptor pathway 1.
Increased Risk Without Benefit
Amplified gastrointestinal side effects: Both medications cause nausea, vomiting, diarrhea, and constipation as their most common adverse effects 3, 5, 6. Combining them would predictably increase these dose-dependent side effects without providing additional therapeutic benefit.
Delayed gastric emptying concerns: Both drugs delay gastric emptying, which could compound risks for aspiration, particularly in perioperative settings 1.
Hypoglycemia risk: While GLP-1 receptor agonists have minimal hypoglycemia risk as monotherapy, combining two incretin-based therapies could theoretically increase this risk, especially if used with insulin or sulfonylureas 1.
The Correct Approach
If Currently on Dulaglutide
Switch to tirzepatide monotherapy: If glycemic control or weight loss goals are not being met with dulaglutide, transition to tirzepatide rather than adding it on top 1, 3.
Tirzepatide is more effective: Clinical trials consistently show tirzepatide 5-15 mg weekly provides superior glycemic control and weight reduction compared to dulaglutide 0.75-1.5 mg 5, 6, 4.
If Additional Glucose-Lowering is Needed
Add a different drug class: If tirzepatide alone doesn't achieve targets, add metformin, SGLT2 inhibitors, or insulin—medications with complementary mechanisms 1.
SGLT2 inhibitors are preferred add-ons: For patients with type 2 diabetes and cardiovascular or kidney disease, adding an SGLT2 inhibitor to a GLP-1 receptor agonist provides proven cardiovascular and renal benefits through distinct mechanisms 1.
Common Pitfall to Avoid
Do not confuse brand names with different mechanisms: Some clinicians mistakenly believe that because Mounjaro and Trulicity have different brand names and tirzepatide has dual GIP/GLP-1 activity, they can be combined. However, the shared GLP-1 receptor activation makes this combination redundant and potentially harmful 2, 3.
Insurance and cost considerations: Mounjaro is FDA-approved for diabetes (and obesity under the brand Zepbound), while some insurance plans may cover one but not the other 1. This should never lead to using both simultaneously—instead, work with the patient to access the single most appropriate agent.