The Matthews protocol is a method of using very small doses of glucagon to raise blood sugar in people with type 1 diabetes when they can’t eat or keep food down. Unlike a standard emergency glucagon injection, which delivers the full vial all at once to treat severe lows, this approach uses a fraction of that dose to gently nudge blood sugar upward. It’s especially popular among parents of children with type 1 diabetes dealing with stomach bugs, nausea, or food refusal.
How It Differs From Emergency Glucagon
Standard emergency glucagon kits are designed for one scenario: a person with diabetes is unconscious or unable to swallow, and their blood sugar is dangerously low. The full emergency dose is 1 mg for adults and children over about 55 pounds, or 0.5 mg for smaller children. That’s the entire vial, injected all at once. It works fast and powerfully, but it also frequently causes nausea (32% of recipients in clinical trials), vomiting (36%), headache, dizziness, and a sharp spike in blood sugar that can last for hours.
The Matthews protocol takes a completely different approach. Instead of using the full vial as a rescue measure, you reconstitute the same glucagon kit but draw up only a tiny amount, measured in insulin syringe units. The goal isn’t to rescue someone from a crisis. It’s to provide a small, steady lift in blood sugar when oral carbohydrates simply aren’t an option, either because the person is vomiting, nauseated, or refusing to eat.
Dosing: 1 Unit Per Year of Age
The core rule is simple: draw up 1 unit of reconstituted glucagon for each year of the child’s age, using a standard insulin syringe. A 4-year-old gets 4 units. A 10-year-old gets 10 units. The dose typically caps at around 15 units for teenagers and adults. For children under 2, a starting dose of 2 units is generally used.
To prepare it, you reconstitute the glucagon kit exactly as the instructions describe, mixing the powder with the included diluent. But instead of injecting all of it, you use an insulin syringe to draw up only the small number of units needed. The injection goes under the skin, just like an insulin shot.
After giving the mini-dose, you check blood sugar every 15 minutes. If blood sugar hasn’t started rising within 15 minutes, or hasn’t reached at least 80 mg/dL within 30 minutes, the dose can be repeated. This careful monitoring and repeat-dosing cycle is what makes it a “protocol” rather than a one-time injection.
When Families Use It
The most common scenario is illness. When a child with type 1 diabetes catches a stomach virus and can’t keep juice or crackers down, blood sugar can drop quickly while insulin (especially long-acting insulin already on board) keeps working. Oral carbohydrates are the standard first-line treatment for low blood sugar, but that’s not helpful when everything comes right back up. Mini-dose glucagon fills the gap between “can’t eat” and “not yet a full emergency.”
It’s also been studied for preventing exercise-related lows. Some people with type 1 diabetes experience drops in blood sugar during or after physical activity, and a small glucagon dose before or during exercise can help stabilize levels without requiring a large carbohydrate load that might cause stomach discomfort mid-workout.
The protocol is most widely used in pediatric type 1 diabetes, where illness-related vomiting is common and children may simply refuse to eat when they feel unwell. But adults with type 1 diabetes use it too, particularly during gastrointestinal illness.
How Long Reconstituted Glucagon Lasts
One practical concern with the protocol is shelf life. Traditional glucagon kits come as a powder that must be mixed with a liquid diluent right before use, and the manufacturer labeling says to use it immediately and discard any leftover solution. This matters because the Matthews protocol uses only a small fraction of the vial, leaving most of it unused.
Research on the chemical stability of reconstituted glucagon tells a more nuanced story. In one study, over 90% of the glucagon remained intact after 24 hours, and about 83% was still present at 48 hours when stored at body-adjacent temperatures. Refrigerated storage appeared to extend usability further. Many families who use the protocol in practice will refrigerate the leftover reconstituted glucagon and use it for up to 24 hours, though this is an off-label approach. The solution should be clear and colorless. If it turns cloudy or develops particles, it should be discarded.
Newer glucagon products, including pre-mixed liquid pens and autoinjectors, don’t require reconstitution and are shelf-stable. However, these products deliver fixed doses and aren’t designed for the tiny incremental dosing that defines the Matthews protocol. Nasal glucagon, which delivers a single 3 mg dose, is similarly a full-dose product not suited to this approach.
Why the Side Effects Are Milder
At full emergency doses, glucagon commonly causes nausea, vomiting, and a dramatic blood sugar spike. In clinical trials of the standard 1 mg subcutaneous dose, 32% of healthy subjects experienced nausea and 36% experienced vomiting. Injection site swelling (58%) and redness (55%) were also frequent.
Mini-dose glucagon sidesteps most of these problems simply because the dose is so much smaller. A 5-year-old receiving 5 units is getting roughly one-twentieth of the full emergency dose. At that level, the blood sugar response is gentler, typically raising levels by 30 to 50 mg/dL rather than causing the sharp overshoot that a full dose produces. Nausea and vomiting, which are dose-dependent side effects of glucagon, are rare at mini-dose levels. This is a meaningful advantage when the whole reason for using the protocol is that the child is already nauseated.
Practical Tips for Using the Protocol
Families who plan to use the Matthews protocol during sick days should keep at least two unexpired glucagon kits on hand, since one kit’s worth of reconstituted solution may not last through a multi-day illness. Having insulin syringes readily available is essential, as the syringe included in the kit is designed for the full dose and isn’t marked in the small increments needed for mini-dosing.
Blood sugar monitoring during the protocol should be frequent. Checking every 15 minutes after a dose lets you know whether a repeat dose is needed and helps you avoid stacking too many doses, which could push blood sugar too high. A continuous glucose monitor simplifies this considerably, though fingerstick checks provide more immediate confirmation when trend arrows are uncertain.
The protocol doesn’t replace the need for emergency glucagon. If a child loses consciousness or has a seizure from low blood sugar, the full emergency dose is still the correct response. Mini-dose glucagon is a prevention and management tool, not a rescue tool. Keeping a separate, untouched kit available for true emergencies is important when you’ve already cracked one open for mini-dosing.