What long-acting insulin (e.g. glargine, detemir, degludec) options are available for patients with diabetes requiring daily insulin therapy?

Long-Acting Insulin Options Available

The long-acting insulin options currently available include insulin glargine (Lantus, Toujeo), insulin detemir, insulin degludec (Tresiba), and NPH insulin, with glargine and degludec providing approximately 24-hour coverage with once-daily dosing. 1, 2, 3

Primary Long-Acting Insulin Formulations

Insulin Glargine (Lantus)

• Insulin glargine U-100 (Lantus) provides peakless basal insulin coverage for up to 24 hours with once-daily administration, typically dosed at the same time each day 1, 2, 4
• The onset of action is approximately 1 hour, with a peakless profile and duration of up to 24 hours 1
• Glargine is absorbed more consistently than NPH insulin and is associated with reduced risk of hypoglycemia, especially nocturnal hypoglycemia 1, 5, 6
• Administered subcutaneously once daily at any time of day, but must be at the same time every day 2
• Cannot be diluted or mixed with other insulins due to its low pH 1, 2

Insulin Glargine U-300 (Toujeo)

• Toujeo (U-300 glargine) provides longer duration of action than Lantus (U-100 glargine), resulting in more stable 24-hour coverage 1
• Demonstrates significantly lower rates of clinically significant hypoglycemia (<54 mg/dL) compared to Lantus in head-to-head trials 1
• Requires approximately 10-18% higher daily doses compared to U-100 glargine to achieve equivalent glycemic control 1
• Preferred for patients experiencing recurrent nocturnal hypoglycemia on Lantus or those with significant glucose variability 1

Insulin Detemir

• Insulin detemir is a long-acting analog that may require twice-daily dosing when once-daily administration fails to provide 24-hour coverage 1
• In type 2 diabetes, detemir reduced severe hypoglycemic events (OR 0.37) and resulted in lower body weight (mean difference -1.26 kg) compared to NPH insulin 7
• In type 1 diabetes, detemir showed statistically significant reduction in severe hypoglycemia compared to NPH insulin 7
• When converting from glargine to detemir, the total daily dose of detemir should be approximately 38% higher than glargine to achieve equivalent glycemic control 8

Insulin Degludec (Tresiba)

• Insulin degludec is an ultra-long-acting analog available in concentrations of 100 units/mL and 200 units/mL 3, 9
• Provides basal insulin coverage with the flexibility of administration at varying intervals (8 to 40 hours between doses in clinical trials) 3, 9
• Demonstrated non-inferiority to insulin glargine U-100 in glycemic control (HbA1c) in both type 1 and type 2 diabetes 3
• The 200 units/mL concentration creates potential risk of confusion and overdose compared to standard 100 units/mL insulins 9

NPH Insulin (Neutral Protamine Hagedorn)

• NPH insulin is the standard long-acting human insulin and the most cost-effective basal insulin option 7, 8
• Typically requires twice-daily administration (before breakfast and at bedtime) to approximate 24-hour coverage 8
• Has a pronounced peak effect, requiring consistent meal timing and carbohydrate content 8
• Associated with higher risk of hypoglycemia, particularly nocturnal hypoglycemia, compared to long-acting analogs 7, 1, 8

Clinical Selection Considerations

Efficacy Comparisons

• In type 2 diabetes, there was no significant difference in HbA1c levels between glargine or detemir compared with NPH insulin, though moderate-quality evidence showed fewer severe hypoglycemic events with glargine (OR 0.65) and detemir (OR 0.37) 7
• Long-acting insulin analogues and NPH insulin had similar effects on HbA1c levels in type 1 diabetes 7
• Insulin glargine achieves equivalent glycemic control to NPH insulin given once or twice daily in both type 1 and type 2 diabetes 5, 6, 10

Hypoglycemia Risk

• Both detemir and glargine reduced risk for severe hypoglycemia in type 1 diabetes, with only detemir showing statistically significant reduction 7
• Insulin glargine is associated with significantly lower incidence of nocturnal hypoglycemia compared to NPH insulin in most clinical trials 1, 5, 6, 10
• Toujeo demonstrates lower rates of clinically significant hypoglycemia compared to standard glargine 1

Cost Considerations

• The World Health Organization recommends human insulin (including NPH) as first-line insulin therapy in low-resource settings, with long-acting insulin analogs like glargine considered only for those who experience frequent severe hypoglycemia with human insulin 7, 1
• NPH insulin is the most cost-effective basal insulin alternative, though insulin glargine costs approximately twice that of NPH insulin on a per-unit basis 8, 6
• The relatively modest overall benefit from insulin analogues is outweighed by the large price difference between human insulin and insulin analogues in resource-limited settings 7

Guideline Recommendations

WHO Recommendations

• Use human insulin (including NPH) to manage blood glucose in adults with type 1 and type 2 diabetes (strong recommendation, low-quality evidence) 7
• Consider long-acting insulin analogues for adults with type 1 or type 2 diabetes who have frequent severe hypoglycemia with human insulin (weak recommendation, moderate-quality evidence) 7

Practical Administration

• Insulin glargine must be used concomitantly with short-acting insulin in type 1 diabetes to address postprandial hyperglycemia 1, 2, 4
• In type 2 diabetes, glargine is often the first insulin introduced as a single daily dose, frequently combined with metformin and possibly one additional non-insulin agent 1, 11
• Some patients may require twice-daily dosing of glargine when once-daily administration fails to provide adequate 24-hour coverage, particularly in type 1 diabetes with high glycemic variability 1