People take GLP-1 medicines for many reasons: type 2 diabetes, heart risk, weight, liver health. Whatever the reason, these medicines act on the hormones that move blood sugar. Here's how that works, using the prescribing information for Ozempic (semaglutide) and Mounjaro (tirzepatide).
What do insulin and glucagon do?
- Insulin is a hormone made by the pancreas that helps glucose (sugar) get into your cells to be used for energy (NIDDK).
- Glucagon works the other way: it causes the liver to release stored sugar into the blood (MedlinePlus).
Think of them as two hands on the same dial. After a meal, your gut releases GLP-1, which tells the pancreas to release more insulin and less glucagon (Holst, 2007). A GLP-1 medicine acts on the same receptor, but it lasts for days instead of minutes.
How does a GLP-1 medicine change insulin and glucagon?
Semaglutide stimulates insulin and lowers glucagon, both in a glucose-dependent way. In the label's words, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. In people with type 2 diabetes, both the fast first wave and the slower second wave of insulin release went up compared with placebo. Glucagon went down by 8% when fasting, 14% to 15% after meals, and 12% over 24 hours.
Tirzepatide acts on two receptors, GIP and GLP-1. Its label says it boosts the first and second waves of insulin release and lowers glucagon, both glucose-dependent. At 15 mg, fasting glucagon fell 28% and glucagon after a mixed meal fell 43% after 28 weeks, with no change on placebo. It also increased insulin sensitivity, meaning the body's cells responded better to insulin, in a clamp study.
“Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated, and glucagon secretion is inhibited.”
What does “glucose-dependent” mean for you?
It means the nudge is tied to your blood sugar. When sugar is high, the medicine pushes insulin up and glucagon down. The Ozempic label also says that during a test where blood sugar was brought low on purpose, semaglutide did not change the body's own glucagon response, the signal that raises sugar back up.
That doesn't mean lows can't happen. They can, especially with some other diabetes medicines. More on that below.
How much does blood sugar change?
- Semaglutide 1 mg, 12 weeks, versus placebo: fasting blood sugar 29 mg/dL (22%) lower, 2 hours after a meal 74 mg/dL (36%) lower, and the 24-hour average 30 mg/dL (22%) lower (Ozempic label, section 12.2).
- Tirzepatide, 40 weeks, on its own (SURPASS-1): A1C fell 1.7 to 1.8 points, versus 0.1 on placebo (Mounjaro label, section 14.2).
Each is one study in people with type 2 diabetes. Your own numbers are something to go over with your care team.
Why does a slower stomach matter for blood sugar?
When food leaves the stomach more slowly, sugar from that meal reaches the blood more slowly too. The Ozempic label says semaglutide delays early stomach emptying after a meal, which reduces the rate at which glucose appears in the blood. The Mounjaro label says tirzepatide delays stomach emptying too, and the delay is largest after the first dose and gets smaller over time.
When can blood sugar go too low?
The labels say the risk of low blood sugar (hypoglycemia) goes up when a GLP-1 is used with insulin or an insulin secretagogue, such as a sulfonylurea. With a sulfonylurea, severe lows happened in 0.8% of people on Ozempic 0.5 mg and 1.2% on 1 mg. The labels say lowering the dose of the insulin or sulfonylurea may be needed. That's your prescriber's call, not something to change on your own.
The Ozempic Medication Guide lists these signs of low blood sugar:
- dizziness or light-headedness, blurred vision
- anxiety, irritability or mood changes
- sweating, shakiness, weakness, feeling jittery
- slurred speech, confusion or drowsiness
- hunger, headache, fast heartbeat
How Checkin helps in your first weeks
Checkin is a free AI companion for GLP-1s that you text. For this part of life on a GLP-1, it does three things:
- Text “took my shot”
It's logged, so you can see your weeks add up.
- It checks in two days after your shot
A quick text to see how you're feeling, timed to your shot day.
- Ask anything
Plain answers from the FDA label, with a picture when it helps.
