Insulin Analogues Glargine and Detemir Differ in Duration

May 22, 2007
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Use of the insulin analogues glargine and detemir can result in better glucose control. However, because glargine and detemir differ from one another, further clinical experience may identify which patient groups will do better on each drug. Dr Matthew C. Riddle recently spoke at an American Diabetes Association meeting and explained what this means for our patients.

Insulin Analogues Glargine and Detemir Differ in Duration
Dr Matthew C. Riddle, Oregon Health & Science University

NEW YORK — Use of the insulin analogues glargine and detemir can result in better glucose control, compared with older human insulins. However, because glargine and detemir differ from one another, further clinical experience may identify which patient groups will do better on each drug, Dr Matthew C. Riddle. said at a meeting sponsored by the American Diabetes Association.

While both drugs have a long duration of effect, that of glargine exceeds 24 hours in most patients, and the drug’s protracted action relates to gradual absorption of microprecipitates from the injection site.

Detemir’s duration of action ranges from 6 hours at low doses of 0.1 unit/kg to approximately 24 hours or longer at higher doses, and its long action results from linkage to a fatty acid chain that permits slower absorption as well as protracted clearance after absorption, said Dr. Riddle, who is head of the section of diabetes and professor of medicine at Oregon Health and Science University in Portland.

Glargine shows less day-to-day variability than does either neutral protamine Hagedorn (NPH) or ultralente insulin, and detemir shows even less, he said. Both analogues also have lower metabolic potency at the insulin receptor, but the reduction for detemir is particularly prominent, he said.

In one blinded study comparing the within-subject variability of NPH, glargine, and detemir in 54 patients with type 1 diabetes, the coefficients of variation were 59% for NPH, 46% for glargine, and 27% for detemir (Diabetes 2004;53:1614–20).

Glargine typically can be given once a day, while more than half of patients on detemir require a second daily injection to maintain adequate control, Dr. Riddle said.

Glargine also can be convenient for initiating therapy, starting at a low dose and titrating up, or for replacing human insulin or in transition from intravenous insulin in the hospital, he said.

“But there are several areas where detemir really could be superior,” he said. For example, for patients with early type 1 diabetes who have a lower insulin requirement overnight but need a blunt peak during the day, detemir could be suitable, since it has a distinct peak of action. However, this peak of action may mean that the timing of meals will be particularly important, he noted. Detemir also could be helpful for patients taking morning prednisone, since its duration would match that of the glucocorticoid.

Detemir’s consistency of action may be especially useful for patients with irregular exercise patterns, although the effects of the analogue insulins with regard to exercise are not yet clear and more studies should be done to answer that question, he said.

Moreover, treatment with detemir is associated with less weight gain than with the human insulins or glargine. This averages about 1 kg less in weight gain, which may be clinically relevant, he said.

It’s also possible that the two drugs could be used together in certain cases. “For example, patients with type 1 diabetes who have a prominent dawn phenomenon could do nicely with an injection of glargine in the morning and detemir at night. Studies have not addressed this yet, but maybe someday we’ll see strategies like that,” Dr. Riddle said. The use of gargine and determir in pregnancy remains controversial.

There is no evidence suggesting that they cannot be used by pregnant women; however, the Food and Drug Administration has not endorsed either drug for that population.

“My opinion and that of about half of diabetes-oriented endocrinologists is that getting glucose control trumps any small and undefined risk of using analogues in pregnancy,” Dr. Riddle said.

There is a possibility that the detemir molecule, unlike the glargine molecule, may cross the blood-brain barrier and may reach the placenta, but this is theoretical, he added.

Dr. Riddle disclosed that he receives research support and acts as a consultant for several pharmaceutical companies, including Sanofi-Aventis, the manufacturer of glargine.