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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 in combination with insulin in patients with type 2 diabetes?
Tirzepatide can be used with concomitant insulin in patients with type 2 diabetes. Concomitant use of tirzepatide with insulin may increase the risk of 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.
Content Overview
What Concomitant Insulins Were Used With Tirzepatide in the Clinical Trials?
What Is the Risk of Hypoglycemia for Tirzepatide in Combination With Insulin?
- Information on Hypoglycemia From the Tirzepatide Prescribing Information
- Information on Hypoglycemia From SURPASS-5: Tirzepatide Use With Insulin Glargine
- Information on Hypoglycemia From SURPASS-6: Tirzepatide Use With Insulin Glargine
How Was the Dose of Insulin Glargine Titrated in the Tirzepatide Clinical Trials?
What Concomitant Insulins Were Used With Tirzepatide in the Clinical Trials?
Eli Lilly and Company has not sponsored clinical studies to evaluate the efficacy and safety of tirzepatide in combination with
- NPH insulins
- premixed insulins, and
- bolus (meal-time) insulins.
What Is the Risk of Hypoglycemia for Tirzepatide in Combination With Insulin?
Information on Hypoglycemia From the Tirzepatide Prescribing Information
Insulin use with or without concomitant therapy is associated with an increased risk of hypoglycemia.3
Patients receiving tirzepatide in combination with insulin may have an increased risk of hypoglycemia, including severe hypoglycemia.4
The risk of hypoglycemia may be lowered by a reduction in the dose of insulin.4
Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.4
Information on Hypoglycemia From SURPASS-5: Tirzepatide Use With Insulin Glargine
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.1
The frequency of hypoglycemia (defined as blood glucose <54 mg/dL [≤3.0 mmol/L], or severe hypoglycemia) in SURPASS-5 was
- 12.5% in the placebo arm
- 15.5% in the tirzepatide 5 mg arm
- 19.3% in the tirzepatide 10 mg arm, and
- 14.2% in the tirzepatide 15 mg arm.1
Information on Hypoglycemia From SURPASS-6: Tirzepatide Use With Insulin Glargine
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.2
The frequency of hypoglycemia (defined as blood glucose <54 mg/dL [≤3.0 mmol/L], or severe hypoglycemia) in SURPASS-6 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.2
The rates of hypoglycemia events per patient-year were lower with tirzepatide than insulin lispro (0.4 vs 4.4 events/patient-year, respectively).2
How Was the Dose of Insulin Glargine Titrated in the Tirzepatide Clinical Trials?
Eli Lilly and Company cannot provide treatment recommendations on how to titrate insulin doses. In formulating an assessment and approach, the health care practitioner may consider
- the patient’s prior medical history and concomitant medications, and
- other individual factors.
The health care practitioner should consider the potential risks and benefits of treatment options and monitor appropriately. The provided information is based on the clinical trial protocols.
Dose Adjustment in SURPASS-5
Prior to randomization, participants in SURPASS-5 were on a stable dose of once-daily insulin glargine with or without metformin.1
Following randomization, there was a 4-week stabilization period, during which insulin glargine dosing was managed as follows:
- for participants with an HbA1c >8.0%, the insulin glargine dose remained unchanged
- for participants with an HbA1c ≤8.0%, the insulin glargine dose was decreased by 20% immediately after randomization and remained unchanged during the stabilization period, and
- additional insulin glargine dose adjustments were permitted using the treat-to-target (TTT) algorithm if hypoglycemia or severe hypoglycemia events occurred.1
From week 4 to 40, the insulin glargine dose was titrated to a fasting blood glucose (FBG) target of <100 mg/dL (5.5 mmol/L) following a TTT algorithm.1
The TTT algorithm in SURPASS-5 involved adjusting the insulin glargine dose based on the median of the last 3 FBG values (see TTT Algorithm in SURPASS-5 for Adjusting Insulin Glargine Dose).1
Median FBG (mg/dL)a |
Median FBG (mmol/L)a |
Adjustment of Insulin Glargine if Dose <20 IU |
Adjustment of Insulin Glargine if Dose ≥20 IU |
≤70 |
≤3.9 |
||
71 to 100 |
4.0 to 5.5 |
No adjustment |
No adjustment |
101 to 119 |
5.6 to 6.6 |
Increase by 1 IU |
Increase by 2 IU |
120 to 139 |
6.7 to 7.7 |
Increase by 2 IU |
Increase by 4 IU |
140 to 179 |
7.8 to 9.9 |
Increase by 3 IU |
Increase by 6 IU |
≥180 |
≥10.0 |
Increase by 4 IU |
Increase by 8 IU |
Abbreviations: FBG = fasting blood glucose; IU = international units; SMBG = self-monitored blood glucose; TTT = treat-to-target.
aBased on the last 3 self-monitored blood glucose values.
bThe insulin dose was also decreased by 1 to 2 IU or 2 to 4 IU if (i) multiple episodes of nonsevere hypoglycemia were recorded during the assessment period at any time during the day; and/or (ii) at least 1 episode that met the criteria for severe hypoglycemia (events requiring assistance of a third person to administer therapy) was associated with SMBG value <54 mg/dL (<3.0 mmol/L) was recorded during the assessment period.
cIf only 1 hypoglycemic episode with SMBG value ≥54 mg/dL (≥3.0 mmol/L) and ≤70 mg/dL (≤3.9 mmol/L) was recorded, insulin dose was not changed.
Dose Adjustment in SURPASS-6
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.2
After randomization, doses of basal insulin glargine were adjusted each week using a titration algorithm to achieve a target FBG of 100 to 125 mg/dL (5.6 to 6.9 mmol/L). Participants adjusted their dose based on the median of the last 3 FBG values measured (see Titration Algorithm in SURPASS-6 for Adjusting Insulin Glargine Dose for information on the titration algorithm used).2
For participants receiving tirzepatide, up-titration of insulin glargine was not allowed for 4 weeks after randomization. Dose adjustments were permitted in cases of hypoglycemia or severe hypoglycemia.2
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 reevaluated every 2 weeks. If participants were not at the target FBG, then insulin glargine was restarted.2
Median FBG (mg/dL) |
Median FBG (mmol/L) |
Adjustment of Insulin Glargine Dose |
≤70 |
≤3.9 |
Decrease by 4 IU |
71 to 99 |
4.0 to 5.5 |
Decrease by 2 IU |
100 to 125 |
5.6 to 6.9 |
No adjustment |
126 to 149 |
7.0 to 8.3 |
Increase by 2 IU |
150 to 179 |
8.4 to 9.9 |
Increase by 4 IU |
≥180 |
≥10.0 |
Increase by 6 IU |
Abbreviations: FBG = fasting blood glucose, IU = international units
Note: The insulin glargine dose was decreased by 4 units for any dose adjustment if a participant experienced any episode of severe hypoglycemia or an FBG value <54 mg/dL (<3.0 mmol/L).
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.2
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.
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Dahl 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
2Rosenstock 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. 2023;330(17):1631-1640. https://doi.org/10.1001/jama.2023.20294
3American Diabetes Association. Standards of care in diabetes—2023. Diabetes Care. 2023;46(suppl 1):S1-S292. https://diabetesjournals.org/care/issue/46/Supplement_1
4Mounjaro [package insert]. Indianapolis, IN: Eli Lilly and Company; 2025.
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: July 18, 2025