Refining basal insulin therapy: what have we learned in the age of analogues?
BACKGROUND
The basal insulin analogues glargine and detemir have been subject to a series of trials comparing their clinical profiles to the conventional preparation, neutral protamine Hagedorn (NPH). Careful review of these trials provides opportunities to learn clinically useful lessons about these insulins.


METHODS
MedLine-indexed trials comparing glargine or detemir to NPH were scrutinized for control, tolerability and dose data. Separate considerations were made for types 1 and 2 diabetes, and for basal-bolus and basal plus oral glucose-lowering drugs (OGLD) therapy. Attention was paid to dosing schedules and 24-h glycaemic profiles.


RESULTS
Collectively, the trials demonstrated an improved balance between glycaemic control and tolerability for both analogues compared to NPH, regardless of regimen and diabetes type. Neither once-daily glargine nor detemir reliably provides 24-h basal insulin replacement in all patients with type 1 diabetes; a waning of effect frequently obliges twice-daily administration. When added to OGLDs in type 2 diabetes, goal-titrated once-daily basal insulin generally lowered HbA(1c) by approximately 1.5%, whereas twice-daily administration tended to increase insulin dose disproportionately to improvement in control. Hence, adding bolus insulin may be a preferable intensification method to dividing the basal dose. Varying injection time or dividing the basal insulin dose predictably affects the pattern of hypoglycaemia and bolus dose requirements. Morning administration tends to require higher dosing than evening administration.


CONCLUSIONS
Scrutiny of trials involving glargine and detemir has increased our understanding of how best to dose basal insulins. An individualized approach is still necessary however, and several questions remain that require further research.
Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands. j.h.devries@amc.uva.nl
J H
JH
Devries
M
M
Nattrass
T R
TR
Pieber
D018849:Controlled Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting
D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; D000069057:Insulin Detemir