Short answer: Low blood sugar (hypoglycemia) is the most common Humalog Mix75/25 side effect, as with all insulin. The label has no trial table with percentages; it lists reactions reported in use: redness, swelling or itching at the injection site, rare severe allergy, low potassium, skin pits or thickening, lumps under the skin, swelling and weight gain. Humalog Mix75/25 has no boxed warning.
What Humalog Mix75/25 is approved for: Humalog Mix75/25 is a premixed insulin approved to improve blood sugar control in adults with diabetes. Its fixed proportions do not allow separate basal and mealtime dose changes (section 1).
Source
HUMALOG Mix75/25 (insulin lispro protamine and insulin lispro) injectable suspension, for subcutaneous use, prescribing information and Patient Information. Eli Lilly and Company. DailyMed, version published August 10, 2026. DailyMed setid c73da51a-1899-45ad-b6cf-9c52c36a25dd
No. The current Humalog Mix75/25 label has no boxed warning.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Humalog Mix75/25.
| Reaction | What the label says |
|---|---|
| Hypoglycemia | The most commonly observed adverse reaction with Humalog Mix75/25 |
| Injection site reactions | Redness, swelling or itching at the site, usually gone in a few days to a few weeks, sometimes needing the insulin to be stopped |
| Meta-cresol reactions | Local reactions and general muscle aches have been reported with meta-cresol, an inactive ingredient |
| Hypersensitivity | Severe, life-threatening whole-body allergy, including anaphylaxis |
| Hypokalemia | Insulin shifts potassium into cells, possibly causing low potassium |
| Lipodystrophy | Lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) |
| Localized cutaneous amyloidosis | Lumps at the injection site; injecting into them has raised blood sugar, and a sudden switch to an unaffected site has lowered it |
| Peripheral edema | Sodium retention and swelling, particularly if poor control is improved by more intensive insulin therapy |
| Weight gain | Attributed to the anabolic effects of insulin and less sugar lost in the urine |
| Starting or tightening control | Temporary change in eye focus, worsening diabetic eye disease and acute painful nerve symptoms |
| Medication errors | Other insulins given by mistake in place of Humalog Mix75/25 |
| Immunogenicity | Anti-insulin antibodies may form; the rate with Humalog Mix75/25 is unknown |
The label gives no rates and no placebo or comparator column for Humalog Mix75/25.
In healthy subjects given 0.3 unit/kg, the median maximum effect came at about 2 hours (range 1-6 hours), and glucose lowering was detectable for a median of 22 hours (range 13 to 22 hours), the end of the study. The label says its duration of activity is similar to Humulin 70/30, and that timing varies between people.
The Patient Information lists the most common side effects as low blood sugar, injection site reactions, skin thickening or pits at the injection site, weight gain, swelling in the hands or feet, itching and rash.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Who should not use it. Humalog Mix75/25 is not used during an episode of low blood sugar, or by people who have had allergic reactions to it or any of its inactive ingredients.
Never share a pen or syringe. A KwikPen is never shared, even if the needle is changed, and vial users never share needles or syringes, because of the risk of passing on blood-borne infections.
Changes in insulin regimen. Changing insulin strength, maker, type, injection site or method can cause high or low blood sugar, so changes are made under close medical supervision with more glucose checks. In type 2 diabetes, other diabetes medicines may need adjusting.
Low blood sugar. Hypoglycemia is the most common reaction to all insulins. Severe episodes can cause seizures, unconsciousness or death and can affect driving. Awareness of lows may be reduced with long diabetes, nerve damage, beta-blockers or repeated lows. Kidney or liver problems can raise the risk.
Medication mix-ups. Mix-ups between insulin products have been reported, so the insulin label is checked before each injection.
Serious allergic reactions. Severe, life-threatening whole-body allergy, including anaphylaxis, can occur; Humalog Mix75/25 is stopped if it does.
Low potassium. All insulins shift potassium into cells and can cause low potassium, which untreated can cause breathing paralysis, heart rhythm problems and death.
Heart failure with TZDs. Thiazolidinediones (such as pioglitazone) with insulin can cause fluid retention that may lead to or worsen heart failure.
From the Patient Information that comes with Humalog Mix75/25:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.