​​​Miriam E.Tucker

First Long-Acting Recombinant Insulin
(Biotechnology Newswatch, July 19, 1999)

A new recombinant DNA insulin analog is being called the "first true basal insulin" by diabetes experts because it provides continuous 24-hour peakless insulin coverage to control blood sugars overnight and between meals.
   
Hoechst Marion Roussel's insulin glargine is a modification of the human insulin molecule in which glycine was substituted for asparagine at the A21 position and two arginines are added to the B30 position. The result is a shift in the isoelectric point and reduced solubility at physiologic pH.
   
The normal pancreas continually delivers insulin to the body all day to maintain metabolic function, and secretes more in response to a meal. 
   
The aim of insulin treatment in people with diabetes is to mimic this natural pancreatic function by injecting long-acting insulin for all-day "basal" coverage along with short-acting insulin "boluses" prior to meals.  However, currently available long-acting human insulin preparations must be taken twice a day, and have variable absorption with pronounced peaks that can cause hypoglycemia. 
   
In Hoechst-funded clinical trials of people with type 1 and type 2 diabetes, once-daily shots of insulin glargine improved fasting blood sugar levels and reduced the number and severity of potentially dangerous nighttime low blood sugars. 
   
On the downside, glargine caused slightly more pain at the injection site than did human insulin, and it can't be mixed in the same syringe with other insulins because it would precipitate them.
   
Hoechst filed a product license application for insulin glargine with the Food and Drug Administration in April, and they expect approval late this year or in early 2000.  If approved, it would be the second biosynthetic insulin analog on the market.  
   
The first one, Eli Lilly's Humalog (lispro), was created by switching lysine and proline in positions 28 and 29 on the insulin beta chain, thereby changing the insulin hexamer into a rapidly-absorbed monomer.  The result is a very short-acting preparation designed to be taken right before meals. Lispro entered the U.S. market in 1996 and is now widely used. ###