Intermediate & Long-Acting Insulin

A patient injects NPH insulin at bedtime and wakes at 3 AM drenched in sweat. Knowing when each basal insulin peaks — or doesn't — tells you why.

Intermediate and long-acting insulins provide basal glucose coverage, mimicking the steady low-level insulin the pancreas normally secretes between meals and overnight. NPH (isophane) is the only intermediate-acting insulin: onset 1–2 hours, peak 4–12 hours (typically 6–8 hours), duration 18–24 hours. That pronounced peak is clinically significant — it creates a predictable window for hypoglycemia, especially overnight when given at bedtime. Glargine (Lantus) and detemir (Levemir) are long-acting analogs: onset 1–2 hours, virtually peakless (glargine) or minimal peak (detemir), duration up to 24 hours (detemir may be shorter — 12–24 hours — and is sometimes dosed twice daily). Degludec (Tresiba) is ultra-long-acting with duration beyond 42 hours. Because glargine precipitates at physiologic pH to form a slow-release depot, it cannot be mixed with any other insulin — doing so destroys the mechanism. NPH is the only insulin that CAN be mixed with rapid- or short-acting insulin in the same syringe. The cloudy appearance of NPH requires gentle rolling (never shaking) to resuspend the crystals. All long-acting analogs are clear solutions. Basal insulins are never used to correct acute hyperglycemia — that role belongs to rapid- and short-acting insulins.

Key Distinctions

Don't confuse NPH's significant peak (4–12 hr, typically 6–8 hr) with glargine's peakless profile — NPH causes nocturnal hypoglycemia, glargine rarely does. Students assume all long-acting insulins can be mixed; only NPH is mixable. Remember: cloudy = NPH = mixable; clear long-acting (glargine, detemir, degludec) = never mix.

Clinical Pearl

Clear and can't mix — that's glargine. Cloudy and can combine — that's NPH. If it's cloudy, roll it; if it's clear and long-acting, draw it alone.