Toujeo (Insulin Glargine U300)

Insulin Glargine U300 (brand name Toujeo) is a long-acting basal insulin analogue. The active substance is the same as in the long-established insulin glargine U100: glycine instead of asparagine at position A21, two additional arginine residues at the end of the B chain. The difference lies purely in concentration. U300 contains 300 units per millilitre instead of 100, so the same number of units sits in one third of the volume.

This information is for research and educational purposes only. No medical advice.

The additional arginine residues shift the molecule's isoelectric point towards neutral pH. In the acidic cartridge solution the substance therefore stays clearly dissolved, while in neutral tissue under the skin it precipitates as a fine microprecipitate. It then dissolves out of that depot slowly over many hours. At the receptor, glargine acts like endogenous insulin: glucose uptake into muscle and fat cells, suppression of hepatic glucose production, inhibition of lipolysis.

Why U300 acts flatter than U100 is pure geometry. One third of the volume means a smaller depot with markedly less surface area relative to its content. Because dissolution of the microprecipitate happens across that surface, the substance is released more slowly and more evenly. A physical property of the formulation thus becomes a pharmacokinetic effect.

This is the most important section on this page. A standard insulin syringe is calibrated for U100. The mark labelled 20 there corresponds to 0.2 ml of a 100-unit solution, that is 20 units. If someone draws a U300 solution to that same mark with that same syringe, 60 units sit in the barrel.

• Threefold overdose: the error is not visually detectable because the scale looks correct and the liquid volume matches.
• Not reversible: with a basal insulin lasting up to 36 hours, an injected amount cannot be corrected for hours.
• The pen is the answer: its counter displays units and delivers one third of the volume per unit. That is exactly what it is built for.
• Without exception: do not transfer into a syringe, do not dilute, do not mix with other insulins, do not store next to U100 products in the same fridge compartment.

Becker et al. compared U300 against U100 in a euglycemic clamp over 36 hours in people with type 1 diabetes at steady state. Under U300, insulin concentration and glucose infusion rate ran more constantly and more evenly distributed across 24 hours, visible in the roughly three hours later time to reach half the area under the curve. Tight blood glucose control lasted a median of about 30 hours, some five hours longer than under U100.

• No pronounced peak: the profile is deliberately flat, not built around a maximum.
• Duration up to 36 hours: clearly beyond the 24-hour window.
• Steady state only after 3 to 4 days: the full effect of a dose change appears with several days of delay.
• Slightly lower relative bioavailability: the EDITION studies needed roughly ten percent more units for the same control.

The EDITION programme tested U300 against U100 in large randomised comparisons. The pattern was the same across all studies: equal blood glucose control, fewer nocturnal hypoglycemic events.

• EDITION 1 (807 participants with type 2 diabetes on basal and mealtime insulin): equivalent reduction in long-term glucose; between week 9 and month 6, 36 instead of 46 percent reported at least one confirmed or severe nocturnal event.
• EDITION 2 (811 participants on basal insulin plus oral antidiabetic drugs): identical reduction at roughly ten percent higher unit dose, fewer nocturnal and fewer any-time events, less weight gain.
• Meta-analysis of EDITION 1 to 3 (2496 people, Ritzel et al.): over six months a 31 percent lower nocturnal and 14 percent lower any-time hypoglycemia rate at identical control. Severe events stayed rare in both groups (2.3 versus 2.6 percent).
• EDITION 4 (549 participants with type 1 diabetes): equivalent control independent of injection time, fewer nocturnal events in the first eight weeks, less weight gain.

Important for context: all of these figures come from treating diabetes. They describe how U300 behaves compared to U100, not how insulin behaves with intact endogenous production.

The risk does not come from unknown side effects, it comes from the main effect. Insulin lowers blood glucose reliably and dose-proportionally and does not stop once a safe value is reached.

• Hypoglycemia: trembling, sweating, palpitations, ravenous hunger, nervousness, then impaired concentration, slurred speech and confusion. With a further drop: seizure, unconsciousness and death. Cognitive impairment sets in precisely when independent corrective action would be needed.
• Long duration as a risk in itself: an excessive basal dose keeps acting for up to 36 hours. A single dose of fast carbohydrates does not cover that window. Hypoglycemia can recur after an initial improvement.
• Preparation is mandatory: glucose tablets, juice or sugary drinks must be within reach before administration. Never without blood glucose measurement, never alone, because a second person present is the last safeguard. Nocturnal events pass unnoticed during sleep.
• Potassium shift: insulin moves potassium into cells. Serum values fall. Marked hypokalemia can trigger cardiac arrhythmias. Carbohydrates alone do not correct that.
• Alcohol and exertion: alcohol suppresses gluconeogenesis in the liver, muscle work increases insulin-independent glucose uptake. Both amplify and prolong the effect considerably.
• Further effects: injection site reactions, lipohypertrophy without site rotation, sodium and water retention with edema at the start, weight change, rarely allergic reactions.

With confusion or clouded consciousness, calling emergency services is the only correct response.

Store unopened in the fridge at 2 to 8 degrees, do not freeze and do not place directly against the freezer compartment. Once in use, keep at room temperature below 30 degrees and protected from light; pens in use do not go back in the fridge. Do not use if the solution is cloudy, discoloured or contains particles. Store separately from U100 insulins so no mix-up can happen in daily handling. Out of reach of children.