Short answer: They can, but on their own it is uncommon, because these medicines raise insulin mainly when blood sugar is high. The risk goes up when they are combined with insulin or a sulfonylurea: in the Ozempic trials, documented low blood sugar with symptoms reached 24.4% on 1 mg plus a sulfonylurea. The Wegovy and Zepbound labels also report low blood sugar in people with type 2 diabetes who were not on insulin, and rare cases in people without diabetes.
The Ozempic label explains that semaglutide raises insulin and lowers glucagon "in a glucose-dependent manner": when blood sugar is high, insulin release goes up. The Mounjaro label says the same of tirzepatide. As blood sugar falls back toward normal, that push eases, which is why low blood sugar is uncommon when these medicines are used alone.
Insulin and sulfonylureas (such as glipizide or glimepiride) work differently: they lower blood sugar whether it is high or not. Add a GLP-1 medicine on top and the two effects stack.
All four labels warn that using them with insulin or an insulin secretagogue, such as a sulfonylurea, may raise the risk of low blood sugar, including severe episodes. They say the risk may be lowered by reducing the dose of the insulin or sulfonylurea, which is a decision for the prescriber. The trial numbers show the size of the difference:
| Trial setting | What was counted | Result |
|---|---|---|
| Ozempic alone, 30 weeks | Documented, with symptoms (70 mg/dL or less) | 1.6% (0.5 mg), 3.8% (1 mg), 0% placebo |
| Ozempic with a sulfonylurea | Documented, with symptoms | 17.3% (0.5 mg), 24.4% (1 mg) |
| Ozempic with basal insulin, 30 weeks | Documented, with symptoms | 16.7% (0.5 mg), 29.8% (1 mg), 15.2% placebo |
| Mounjaro alone, 40 weeks | Below 54 mg/dL | 0% on each dose, 1% placebo |
| Mounjaro with basal insulin, 40 weeks | Below 54 mg/dL | 16%, 19% and 14% (5, 10, 15 mg), 13% placebo |
| Mounjaro with a sulfonylurea, up to 104 weeks | Below 54 mg/dL | 13.8%, 9.9% and 12.8% (5, 10, 15 mg) |
Severe episodes, meaning someone else had to help, were rare in these trials: up to 1.2% with Ozempic plus a sulfonylurea and up to 2% with Mounjaro plus basal insulin.
The weight-loss labels describe low blood sugar in people with type 2 diabetes who were not on insulin. In the Wegovy trial, blood sugar below 54 mg/dL was reported in 6.2% on Wegovy versus 2.5% on placebo. In the Zepbound trial it was 4.2% versus 1.3%, and among people on Zepbound it was 10.3% for those also taking a sulfonylurea against 2.1% for those who were not.
For people without diabetes, the trials did not systematically collect low blood sugar. The Zepbound label reports blood sugar below 54 mg/dL in 0.3% of people on Zepbound versus none on placebo in its main trial. The Wegovy label reports 3 serious episodes on Wegovy versus 1 on placebo in a heart outcomes trial of people without diabetes, and more serious episodes in people who had had weight-loss surgery (2.3%, 2 of 87, versus 0 of 97 on placebo). It calls past weight-loss surgery a risk factor for low blood sugar.
The Wegovy and Zepbound labels say that in people with diabetes, blood sugar should be checked before starting and during treatment.
The patient leaflets list these signs of low blood sugar: dizziness or light-headedness, sweating, confusion or drowsiness, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability or mood changes, hunger, weakness, and feeling jittery.
The Wegovy leaflet says low blood sugar in people with type 2 diabetes can be "both a serious and common side effect", and to talk with your healthcare provider about how to recognize and treat it. If you also take insulin or a sulfonylurea, ask your prescriber whether those doses need to change when you start or step up a GLP-1 medicine. Dose Track keeps glucose readings, doses and symptoms on one timeline.
Read more on Dose Track: Blood sugar · Ozempic side effects · Mounjaro side effects · Zepbound side effects · HbA1c (glossary) · GIP (glossary)