Rapid Insulins for Diabetes

Humalog^® and Novolog^® Insulins

by John Walsh, P.A., C.D.E. and Ruth Roberts, M.A.

Humalog, Novolog and Regular Compared
Differences Between Humalog and Novolog
Tips For Fast Insulins
Additional Pump Information
Storage Issues
Clinical Research Findings

See also Kinetics vs. Dynamics, Humalog & Heat and Users’ Reports

Like Regular, Humalog and Novolog are used to cover meals and snacks. Most meals raise the blood sugar for only 2 to 3 hours afterward. Once injected, Regular insulin takes 30 minutes to begin working, peaks between 2 and 4 hours, and hangs on for 6 to 8 hours after the meal stops raising the blood sugar. Humalog and Novolog, on the other hand, begin working in about 10 minutes, peak at one to one and a half hours, and are gone in about three and a half to four hours.

Many people who’ve tried these faster insulins report that their control is improved and that they feel better. The great advantage of fast insulins is that they match the “action time” for most meals. You can take them as you begin eating rather than the 30 to 45 minutes before eating as required for regular eating. No longer do you need to accurately anticipate when you (or your young child with diabetes) will begin eating. In addition, Humalog and Novolog leave your body faster, so you don’t have residual insulin, which causes low blood sugars in the late afternoon or, even worse, in the middle of the night.

For most meals, fast insulin lowers blood sugar at the same time the food raises it. The rise in blood sugar seen a couple of hours after eating is much lower, especially with Novolog, and by the end of three hours, the blood sugar is often back to its starting point.

With Humalog or Novolog, you’re better equipped to prevent spiking blood sugar between meals while avoiding the lows that result from the combined buildup of Regular and long-acting insulins. The new Lantus insulin is an excellent choice when using these fast insulins to cover meals. The clearly defined action times for the fast insulins make it easier to adjust meal doses correctly.

Humalog and Novolog are also excellent insulins for lowering high blood sugars. Their faster action means less time is spent at high blood sugar levels, and less residual insulin will trigger low blood sugar later.

Lilly produced Humalog, which was first released in the U.S. in 1996, while Novolog was made by Novo Nordisk and was released in 2001. Both insulins offer quicker action time than the original “short-acting” Regular insulin, which became available in 1921. However, users also report significant activity differences between the three insulins. Let’s first look at these differences.

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Differences Between Humalog And Novolog Versus Regular

When using injections, Humalog, Novolog, and Regular are primarily used to cover meals and snacks and to lower high blood sugars. Most meals create a rise in the blood sugar for only a short period of time, normally 2 to 3 hours. Regular insulin, available since 1922, takes 30 minutes to start working, peaks at 3 to 4 hours after the injection, and continues lowering blood sugars for 6 to as much as 8 hours. Humalog, on the other hand, begins working in 10 minutes, peaks at one to one and a half hours, and is gone in about 3 and 1/2 hours. Novolog insulin has an even faster onset of action and peaks in 40 to 75 minutes, which surprised many when they switched from Humalog to Novolog.

The great advantage of the faster insulins is that they can be taken as you begin eating, rather than the 30 to 45 minutes beforehand that is required of Regular. The activity of Humalog and Novolog matches the “action time” for most meals. For mothers of small children and those on the go, this is a tremendous advantage. Rather than having to lead the unpredictable timing of meals, people can now wait until the meal begins. Those feeling ill can simply wait to cover food they are unsure of keeping down. Kids who are picky eaters can be given their dose after they finish the meal with little loss of control.

Humalog and Novolog make a much better match with meals, lowering the blood sugar while food is raising it. Blood sugars measured one to two hours after eating do not spike as high as they do with Regular, and by the end of the third hour, the blood sugar can be close to its starting point. The faster action time of these two insulins means the insulin action from the previous meal bolus is gone before the next meal begins.

Compared to regular insulin, both fast insulins offer the advantage of having less insulin activity before going to bed with fewer nighttime reactions. Humalog and Novolog leave your body more quickly, so you don’t have residual insulin, which causes low blood sugar levels in the middle of the night. You are better equipped to stop spiking between meals and are no longer exposed to the overlapping buildup of Regular boluses. However, for those paying for their insulin, price shock can be significant. Humalog and Novolog are typically priced at about $60 a bottle, while Regular can be obtained as low as $18 a bottle.

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Differences Between Humalog Versus Novolog

Users have reported a couple of major differences between Novolog and Humalog. Especially among pumpers who switch from Humalog to Novolog, reports have surfaced that Novolog appears to be both stronger and quicker than Humalog. Doses have to be cut to prevent hypoglycemia. Dose reductions are often in the 10% range, and it may be wise to reduce doses right away to prevent unwanted lows. If blood sugars rise instead, doses can always be raised again.

Novolog also starts working faster than Humalog. Although no direct comparison of Novolog and Humalog has been reported, one research study found that in normal individuals, Novolog reaches peak activity at 52 minutes, compared to 145 minutes (2 hours and 25 minutes) for Regular insulin. Humalog peaks at about 75 minutes (Eur J Clin Pharmacol 1999 May;55(3):199-203). Both pumpers and injectors may note lower post-meal readings due to the faster onset of action.

The clearly defined action times of the fast insulin make it easier to troubleshoot problems. For information on determining the carbs covered by each unit, see the Carb Factor – 2.6 Rule. Humalog and Novolog are also excellent for lowering high blood sugar, with less time spent at high blood sugar levels and less residual insulin left to trigger low blood sugars later. For information on how to safely lower highs, see the 1800 Rule,

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Tips For Fast Insulins

Test often. Test your blood sugar often to determine how fast insulins work best. As you start using Humalog or Novolog, it is wise to test before eating, 2 hours after eating, and any time you experience unusual symptoms. Test often and use special caution when lowering high blood sugars. Be alert for lows one or two hours after a meal and at other unexpected times.

Cover food differently. The great advantage of faster insulins is their convenience. Although a 10 to 20-minute lead time is ideal, doses and boluses can be taken with the first bite of food with good post-meal control. Of course, their quick action means that you must not delay eating! If the premeal blood sugar is high and eating is delayed to allow the blood sugar to drop, the food must be eaten at the time planned to avoid low blood sugar.

Foods that have a high glycemic index and raise blood sugar quickly, like cold cereals or a scone for breakfast, are easier to cover with fast insulins. On the other hand, when low glycemic carbohydrates like pasta al dente or a bean burrito are eaten, the blood sugar may go low before these foods can completely digest. For occasional foods with a low GI, doses or boluses can be split. Take half before the meal and the second half an hour or two after eating. Pumps also have dual or extended boluses to stretch out insulin action. Another option is to use an injection of Regular to match slow carbohydrates. Meals with high-fat content may also occasionally need similar coverage. If your blood sugar is low or on the edge of low at mealtime, eat the meal and take a slightly reduced dose of fast insulin afterward.

Treat lows differently. Because of their faster action, fast carbs are recommended when treating low blood sugars. Glucose tabs, honey, or candies with dextrose, like Sweet Tarts, work best. Low blood sugars usually occur within 3 to 3 and 1/2 hours. If a low blood sugar occurs one or two hours after a dose or bolus, more carbohydrates will be needed to raise the reading back to normal than if the low happens three or four hours after the bolus. At three hours, a small amount of carbohydrates (10 to 20 grams) is usually needed to remedy the situation.

Another great benefit of fast insulins is that fewer lows are experienced during the night. When people used Regular to cover dinner, they often needed a bedtime snack to avoid a low during the night. In contrast, Humalog and Novolog can be used at dinner with little need for a bedtime snack if the nighttime insulin is correctly set.

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Additional Pump Information

Several research studies previously reported that boluses remained the same when people switched from Regular to Humalog. However, there were several reasons to be alert for changes that may be needed. When switching from Regular or Humalog to Novolog, however, reducing basals and boluses by about 10% is wise when the switch is made. With either fast insulin, but especially with Novolog, less insulin is needed to cover the same number of grams of carbohydrate. Compared to regular insulin, the shorter action time seen with boluses of fast insulins often requires a higher daytime basal rate. With Humalog and Novolog, the basal rate usually makes up 50% to 60% of the total daily insulin dose.

In research on Humalog’s biological activity, two of six studies found that Humalog was as much as 10% more active than Regular in lowering blood sugars. In contrast, the other four found its activity was identical to Regular. Be alert if a unit of Humalog seems to go farther than a unit of Regular. Any change in insulin doses should only be attempted after discussing them thoroughly with your physician.

Many pumpers using Humalog report they need slightly less insulin throughout the day. Some find boluses may need to be reduced by 10 to 25%. Basal rate amounts generally don’t change, although some find they need to raise the basal rate in the late evening and early nighttime hours because they used to rely on Regular’s long action to work into the nighttime hours.

With Humalog’s greater speed, basal rate changes are made closer to the needed time. For instance, on Regular, if the basal rate is raised at 2 a.m. to offset a Dawn Phenomenon, raising the basal rate might be delayed until 3 a.m. on Humalog. With Novolog, many pumpers report they need to delay any rise in basal rates forward by an hour or two to prevent lows. For example, if the basal rate is normally raised at 3 am on Humalog, it would be delayed until 4 am or 5 am on Novolog.

For safety’s sake, do not use the suspend feature with Humalog for exercise or low blood sugar. If you forget to take it out of suspension, you can quickly have high blood sugar. Because of its short action time, blood sugars typically begin to rise 60 to 90 minutes after the insulin is suspended unless a bolus was taken recently. Another reason to never use suspend is that insulin that is static in the infusion line encourages clogging.

Always inject Humalog at the FIRST high blood sugar reading over 300 mg/dl (17 mmol). If any delivery problem occurs with Humalog in your pump, blood sugars can start to rise within 60 to 90 minutes, and ketoacidosis can begin in 4 to 5 hours. If a SECOND reading taken 90 to 120 minutes later is still over 300 mg/dl, take Humalog by injection and change out the reservoir and infusion set.

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Clinical Research Findings

Results from 23 clinical research studies using Humalog in Europe, Canada, and the United States were reported at the 1997 American Diabetes Association meeting in Boston. Our analysis of these studies found positive results in four areas when comparing Humalog with Regular:

1. Humalog gives better readings 1 to 2 hours after meals. Usually, Humalog is given at the start of a meal. Still, even when taken 15 minutes after a meal, Humalog gives better postmeal readings compared to Regular, which is taken 40 minutes before a meal.
2. Blood sugars are improved throughout the day due to improved readings after meals.
3. An average of 0.5% lowers the HbA1c.
4. Humalog improves quality of life.

Other results in individual studies were also positive. In one study, two people who had hypoglycemia unawareness regained warning symptoms of low blood sugar. In a study of adolescents, incidents of nighttime hypoglycemia decreased.

The subjects in most of the research studies above were Type 1s on long-term intensive management who had good control of HbA1cs in the 7s or 8s before using Humalog. However, one study followed people with “brittle diabetes” with erratic blood sugars and high HbA1c. On switching to Humalog from Regular, their diabetes improved in all four areas listed above. Another study using people with Type 2 diabetes reported these improvements, and the subjects had no weight gain.

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Cautions About Heat And Storage

Some people have noticed unexpected high blood sugars with Humalog and report that Humalog may deteriorate faster in hot weather than Regular or Novolog. Control problems can occur for other reasons, such as incorrect basals and boluses that do not match the need for insulin. However, Humalog appears less stable and more likely to lose activity, especially when exposed to heat or excess cold. Test often, and if your insulin does not appear to have the expected effect, check for particles in the bottle and open a new bottle.

Though rare, when Humalog goes bad, it does so quickly. Blood sugars may be fine one day and high the next. If they are unexpectedly high, check for particles in the bottle. These are usually seen as one or two large floaters or several small crystals in solution or on the sides of the bottle. Always start a new bottle if you have any doubts.

In summary, most shooters and pumpers have gladly welcomed the newer fast insulins. Most have also been impressed by improvements in their control and in the convenience of taking their insulin right before they eat. Fewer lows at night and improved HbA1c reports are a few of the benefits pumpers have experienced, and most report they feel better on fast insulins.