From the Research
Morning administration of NPH insulin is not recommended due to the significant risk of midday hypoglycemia, and instead, it is typically recommended for evening or bedtime administration. NPH insulin has an onset of action within 1-2 hours, peaks at 4-8 hours after injection, and has a duration of 12-18 hours. When administered in the morning, the peak insulin effect occurs during midday, which often doesn't align with meal timing and can lead to dangerous blood glucose drops between lunch and dinner. This risk is particularly concerning because midday hypoglycemia may occur when patients are active, driving, or working, potentially leading to serious consequences.
The most recent and highest quality study, a 2020 Cochrane Review update 1, compared the effects of long-term treatment with (ultra-)long-acting insulin analogues to NPH insulin in adults with type 2 diabetes mellitus. The review found that insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin, with a risk ratio for severe hypoglycaemia of 0.68 (95% confidence interval 0.46 to 1.01) for insulin glargine and 0.45 (95% CI 0.17 to 1.20) for insulin detemir.
Some key points to consider when administering NPH insulin include:
- NPH insulin peaks at 4-8 hours after injection, which can lead to midday hypoglycemia if administered in the morning
- Evening or bedtime administration can help control fasting blood glucose levels overnight and reduce the risk of hypoglycemia
- Rapid-acting insulins before meals or longer-acting basal insulins with flatter profiles (like insulin glargine or detemir) are generally safer options for patients requiring morning insulin coverage
- The 2020 Cochrane Review update 1 provides the most recent and highest quality evidence on the comparison of (ultra-)long-acting insulin analogues to NPH insulin in adults with type 2 diabetes mellitus.
In terms of specific administration timing, a study from 2002 2 found that administering NPH insulin at bedtime instead of with dinner reduced the risk of nocturnal hypoglycemia and improved glycemic control in patients with type 1 diabetes mellitus. Another study from 2006 3 found that converting from bedtime NPH insulin to morning insulin glargine improved glycemic control in type 2 diabetic patients on basal-prandial insulin therapy. However, the most recent and highest quality evidence from the 2020 Cochrane Review update 1 should be prioritized when making clinical decisions.