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Mounjaro ® (tirzepatide) injection
2.5 mg/5 mg/7.5 mg/10 mg/12.5 mg/15 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
Can Mounjaro® (tirzepatide) be used with concomitant basal insulin in adults with type 2 diabetes (T2D)?
Tirzepatide can be used with concomitant insulin in patients with T2D. However, concomitant use of tirzepatide with insulin increases the risk of hypoglycemia, including severe hypoglycemia, which may be lowered by a reduction in the dose of insulin.
See important safety information, including boxed warning, in the attached prescribing information.
Tirzepatide Use With Insulin
Insulin use with or without concomitant therapy is associated with an increased risk of hypoglycemia.1
Patients receiving tirzepatide in combination with insulin may have an increased risk of hypoglycemia, including severe hypoglycemia.2
The risk of hypoglycemia may be lowered by a reduction in the dose of insulin.2
Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.2
Use With Insulin Glargine in SURPASS-5
SURPASS-5 was a 40-week, phase 3, double-blind, randomized study of tirzepatide 5, 10, and 15 mg once weekly compared with placebo in 475 adults with type 2 diabetes (T2D), as add-on to titrated insulin glargine with or without metformin.3
Insulin glargine was titrated in all arms during the insulin titration period from week 4 to 40 following a treat-to-target algorithm with the goal of fasting serum glucose (FSG) <100 mg/dL.3
In SURPASS-5, insulin glargine dose
- increased by 25.1 international units (IU)/day in the placebo arm
- increased by 4.4 IU/day in the tirzepatide 5 mg arm
- increased by 2.7 IU/day in the tirzepatide 10 mg arm, and
- decreased by 3.8 IU/day in the tirzepatide 15 mg arm.3
In SURPASS-5, hypoglycemia (defined as blood glucose ≤70 mg/dL) frequency was
- 60.8% in the placebo arm
- 60.3% in the tirzepatide 5 mg arm
- 63.0% in the tirzepatide 10 mg arm, and
- 60.0% in the tirzepatide 15 mg arm.3
Use With Insulin Glargine in SURPASS-6
SURPASS-6 was a 52-week, phase 3b, open-label, multicenter, parallel-group, randomized study of tirzepatide 5, 10, and 15 mg once weekly compared with insulin lispro in 1428 adults with T2D as add-on to titrated insulin glargine with or without metformin.4
For SURPASS-6, all study participants were on a standardized therapy of basal insulin glargine with or without metformin for up to 10 weeks prior to randomization to tirzepatide or prandial insulin lispro.5
- At randomization, participants in all groups decreased their insulin glargine dose by 30% to reduce the risk of hypoglycemia during introduction of the treatment drug. Doses of basal insulin glargine were adjusted each week using a titration algorithm to achieve a target fasting blood glucose (FBG) of 100 to 125 mg/dL.4
- For participants receiving tirzepatide, up-titration of insulin glargine was not allowed for 4 weeks after randomization.4
- Participants achieving the target FBG for 2 consecutive weeks with a low dose of insulin glargine (<10 units) could temporarily interrupt insulin glargine injection based on the investigator decision. Participants continued to measure required FBG for insulin glargine dose adjustment and were re-evaluated every 2 weeks. If participants were not at the target FBG, then insulin glargine was restarted.4
At randomization, the overall insulin glargine dose was 47 IU.4
As presented in SURPASS-6: Daily Insulin Use Over Time, the basal insulin glargine dose decreased over time with tirzepatide treatment. At week 52, the proportion of participants who were no longer receiving insulin glargine background therapy was
- 8% for tirzepatide 5 mg
- 14% for tirzepatide 10 mg, and
- 19% for tirzepatide 15 mg.4
Figure 1 description: Through 52 weeks, the daily insulin glargine dose was lower in participants receiving tirzepatide compared with insulin lispro and decreased over time for all treatment groups.
Abbreviations: iLispro = insulin lispro; IU = international units; TZP = tirzepatide.
Notes: Data are presented as geometric mean (95% CI). Colored arrows denote timing of TZP dose escalation for the corresponding TZP dose. Data in parentheses are IU/kg. TZP Pooled refers to pooled data for the TZP 5 mg, 10 mg, and 15 mg groups.
In SURPASS-6, hypoglycemia, blood glucose <54 mg/dL, or severe hypoglycemia frequency was
- 12% in the tirzepatide 5 mg arm
- 9% in the tirzepatide 10 mg arm
- 11% in the tirzepatide 15 mg arm, and
- 48% in the insulin lispro arm.4
Rates of hypoglycemia event per patient-year were lower with tirzepatide than insulin lispro (0.4 vs 4.4 events/patient-year, respectively).4
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1American Diabetes Association. Standards of care in diabetes—2023. Diabetes Care. 2023;46(suppl 1):S1-S292. https://diabetesjournals.org/care/issue/46/Supplement_1
2Mounjaro [package insert]. Indianapolis, IN: Eli Lilly and Company; 2023.
3Dahl D, Onishi Y, Norwood P, et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial. JAMA. 2022;327(6):534-545. https://doi.org/10.1001/jama.2022.0078
4Rosenstock J, Frías JP, Rodbard HW, et al. Tirzepatide vs insulin lispro added to basal insulin in type 2 diabetes: the SURPASS-6 randomized clinical trial. JAMA. Published online October 3, 2023. https://doi.org/10.1001/jama.2023.20294
5Rosenstock J, Frias JP, Rodbard HW, et al. “SURPASS(ing)” an era of basal-bolus insulin therapy: tirzepatide vs insulin lispro TID added-on to poorly controlled basal insulin-treated type 2 diabetes! Poster presented at: 83rd Scientific Session of the American Diabetes Association; June 23-26, 2023; San Diego, CA, USA.
Date of Last Review: September 06, 2023