When Hypoglycemia (when combined) on Mounjaro Becomes a Reason to Stop

What the Mounjaro label says about low blood sugar

Section 5.3 of the Mounjaro label says that patients taking Mounjaro with an insulin secretagogue such as a sulfonylurea, or with insulin, may have an increased risk of hypoglycemia, including severe hypoglycemia. It states that the risk may be lowered by a reduction in the dose of the sulfonylurea or insulin, and that patients on those drugs should be told about the risk and taught the signs and symptoms of hypoglycemia [1].

Section 7.1 repeats the instruction at the point of starting treatment: when initiating Mounjaro, consider reducing the dose of the insulin secretagogue or insulin to reduce hypoglycemia risk [1]. Neither section states an amount for the reduction, and neither contains an instruction to discontinue Mounjaro [1].

Where the label does say to discontinue Mounjaro

The warnings section says to discontinue Mounjaro if acute pancreatitis is suspected, and to discontinue it if hypersensitivity reactions occur [1]. The hypoglycemia warning is separate from both, and the lever it names is the dose of the insulin secretagogue or insulin [1].

What the trials show about lows

In the label's placebo-controlled adult trials, glucose under 54 mg/dL occurred as follows [1]:

• SURPASS-1 (Mounjaro alone, 40 weeks): 1% on placebo and 0% on 5 mg, 10 mg and 15 mg, with no severe hypoglycemia [1].
• SURPASS-5 (added to basal insulin, 40 weeks): 13% on placebo, 16% on 5 mg, 19% on 10 mg and 14% on 15 mg. Severe hypoglycemia was reported in none of the placebo or 5 mg patients, 2% on 10 mg and 1% on 15 mg [1].

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

Why insulin and sulfonylureas carry the risk

A review of GLP-1-based therapies notes that these drugs slow gastric emptying, which lowers post-meal glucose but carries a potential risk of hypoglycemia in people on insulin or sulfonylurea therapy [2]. That is the combination the label warns about, and the adjustment it recommends is on the companion drug [1].