Basal Insulins for treating diabetes mellitus, from discovery to modernity
Basal insulin is also referred to as background insulin. It is that insulin which the pancreas produces and is present all the time. In contrast, bolus insulin is the extra amount of insulin the pancreas produces in response to glucose intake. In patients with T1DM, the pancreas stops making insulin and the patient needs to inject it. In patients with T2DM, the pancreas continues producing insulin but it may be in insufficient quantities or the body may be resistant to its effects.
Basal, or continuously acting, insulin is a mainstay of treatment in patients with both T1DM and T2DM. While basal insulin medications have been available for decades, recent years are seeing new ones come to market.
What are the basal insulins?
NPH: In 1923, Hans Christian Hagedorn and August Krogh founded the Nordisk Insulin Laboratorium and obtained the rights to develop insulin therapy. In 1936, Hagerdorn and B. Norman Jensen discovered the effects of injected insulin could be prolonged with the addition of protamine. They licensed protamine zinc insulin (PZI) and sold it to several manufacturers. Its effects lasted 24-36 hours. In 1946, Nordisk was able to form crystals of the protamine and insulin and marketed it as NPH insulin. This NPH insulin had a faster onset of action and could be mixed with other insulins. Today, Novo Nordisk replaced all animal insulins with recombinant human insulin.
NPH human insulin has an onset of action of 1 to 2 hours. It reaches its peak at around 8 hours and has a duration of action of 12 or more hours. The higher the dose, the longer it is to peak effect and the longer is the duration of action. NPH insulin can be premixed with regular insulin or a rapid-acting insulin analog. It is typically administered twice a day.
Glargine: This basal insulin was developed in Sanofi-Aventis’ biotechnology lab in Germany. It represents Germany’s largest and most important pharmaceutical export and is used by over 3.5 million people in over 100 countries. It was first marketed world-wide in 2005. It is a recombinant human insulin analog and when it is injected, it forms microprecipitates in the subcutaneous tissues. From these, small amounts of insulin glargine are slowly released over 24 hours. Because of relatively constant concentration/time profile, no peak effect is observed. Interestingly, it is produced using a labroratory strain of E. coli (K12) as the production organism. It differs from human insulin by the fact that asparagine at the A21 position is replaced by glycine and 2 arginines and added to the C-terminus of the B-chain. Its onset of action is 1.5 hours.
Detemir: This basal insulin does not form microprecipitates when it is injected into the subcutaneous tissues. It is absorbed from the injection site slowly over 24 hours. It binds with albumin in the blood stream. This binding helps prevent it from rapid or irregular insulin absorption. Its onset of action is 1 hour with no peak and its duration of action is 12-24 hours. (A complete list of all available insulins can be found here.)
Commonly prescribes insulins
The most commonly prescribed insulins are referred to U100 insulin. This means that there are 100 units of insulin dissolved in 1 ml of liquid. These include NPH, glargine, degludec, and detemir as well as short-acting human regular insulin and short-acting inulin analogs (lispro, aspart, glulisine). The newest long-acting insulins are important because they provide sustained glucose lowering without increased risk of hypoglycemia. Additionally, the newer agents help overcome severe insulin resistance.
One study conducted in patients with T2DM looked at safety in patients who were previously treated with insulin alone. The improvement in HbA1C was similar in the treatment group receiving glargine as compared to the control group maintained on NPH insulin. In the patients treated with glargine, the incidence of nocturnal hypoglycemia was 25% lower than the control group. Additionally, they experienced less weight gain.
For decades, insulin has been a gold standard of treatment in diabetic patients. We have seen how insulin has evolved since that time and it continues to do so. Recent studies indicate that an inhaled form of insulin will soon be available for routine use. As clinicians, we all know the terrible consequences diabetes can cause. It is as imperative now as it has ever been to have safe and effective treatment. In the 21st Century, it is also key to have easy to use medications so that patients will actually take them.
About the Author
Linda Girgis MD, FAAFP is a family physician practicing in South River, New Jersey. She was voted one of the top 5 healthcare bloggers in 2016. Follow her on twitter @DrLindaMD.