Hypoglycemia (when combined) on Mounjaro (tirzepatide for T2D): Incidence, Severity, and Realistic Expectations

What the Mounjaro label says about low blood sugar

Mounjaro is the tirzepatide product approved for type 2 diabetes in adults and children 10 years and older, and for reducing the risk of major cardiovascular events in adults with type 2 diabetes at high risk of those events [1].

The warning is titled 'Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin' [1]. It says patients receiving Mounjaro with an insulin secretagogue such as a sulfonylurea, or with insulin, may have an increased risk of hypoglycemia, including severe hypoglycemia, and that the risk may be lowered by a reduction in the dose of the sulfonylurea or other insulin secretagogue, or of insulin [1]. It adds that these patients should be informed of the risk and taught the signs and symptoms of hypoglycemia [1].

The drug interactions section repeats it as a step for the start of treatment: when Mounjaro is initiated, the label says to consider reducing the dose of the concomitantly administered insulin secretagogue or insulin to reduce the risk of hypoglycemia [1]. Neither section states a specific reduction amount [1].

How often low blood sugar happens

The label's table of common adverse reactions is presented 'not including hypoglycemia', and the label reports hypoglycemia separately [1]. Its placebo-controlled adult trials were SURPASS-1, a 40-week monotherapy trial, and SURPASS-5, a 40-week trial of tirzepatide added to basal insulin with or without metformin [1]. The label reports the share of patients with glucose under 54 mg/dL at least once [1]:

• SURPASS-1 (Mounjaro alone): 1% on placebo and 0% on 5 mg, 10 mg and 15 mg [1].
• SURPASS-5 (added to basal insulin): 13% on placebo, 16% on 5 mg, 19% on 10 mg and 14% on 15 mg [1].

The label also states that hypoglycemia was more frequent when Mounjaro was used with a sulfonylurea [1].

A different tirzepatide product, Zepbound, has a label that gives a sulfonylurea comparison from SURMOUNT-2, a trial in adults with type 2 diabetes and obesity or overweight: hypoglycemia (glucose under 54 mg/dL) occurred in 10.3% of patients on a sulfonylurea versus 2.1% of those not on one. That is a Zepbound trial population, not a Mounjaro one.

Why the risk is higher with these drugs

A review of GLP-1-based therapies notes that these drugs slow gastric emptying, which lowers after-meal glucose but also carries a potential risk of hypoglycemia in people on insulin or sulfonylurea therapy [2].

Severe low blood sugar

The label's wording separates the two: it warns of hypoglycemia 'including severe hypoglycemia' when Mounjaro is used with these drugs [1]. In SURPASS-5, severe hypoglycemia was reported in 2% of patients on 10 mg and 1% on 15 mg, and in none on placebo or 5 mg; none was reported in SURPASS-1 [1].

Outside the trial program, one small retrospective study followed 62 adults with type 1 diabetes, a group Mounjaro is not approved for, who were prescribed tirzepatide off label for a year. It reported no hospitalizations for severe hypoglycemia, and insulin doses fell [3].