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"Ideally, I should wait," said Wright, a bit sheepishly, "but I just don't have the time." Living with diabetes is hassle enough, so counting the minutes before mealtime is not always a priority; it's just not convenient.
Wright is not alone. Current studies suggest that nearly 50 percent of all insulin users are willing to run the risk of fluctuating blood sugars by injecting closer to mealtime.
But with the advent of Lispro, the fastest-acting insulin on the market, waiting, and the risks of injecting too soon before meals, may be a thing of the past.
Lispro, brand-named Humalog, is designed to mimic the body's natural insulin output in response to eating. Because of its rapid action, patients can take Lispro 15 minutes before meals, instead of waiting like they should with regular insulin.
Using Lispro, "it's easier to be impulsive without getting high blood sugars," Wright said. There's less trouble when you go out to a restaurant, no more taking your insulin at home or in the car. You can take it right at the table.
But Lispro's fast-acting ways-the very quality the new insulin is touted for-is what scares some people most.
If there's not enough food in the system when Lispro goes to work, blood sugars can drop fast. The result? A severe hypoglycemic episode. "What happens if the phone rings and the baby cries in the middle of a meal, thus delaying eating after injecting Lispro? Is there enough time to deal with it when the insulin acts so quickly?" wonders Jenny Hirst, co-chair of England's Insulin Dependent Diabetes Trust.
Physicians say this has not been a problem for people who used the new insulin during the research phase, but the very fact that the risk exists has made some within the diabetes community less enthusiastic about the arrival of Lispro.
Developed by pharmaceutical giant Eli Lilly, Lispro is the first new insulin in 14 years. Originally introduced in Russia in April 1995, it was released in the United States in August. Lispro was made faster acting by changing the order of two amino acids-lysine and proline- in the human insulin molecule, thereby accelerating its absorption rate. Some say Lispro is what regular insulin was always meant to be, but wasn't-truly fast-acting.
The new insulin will not be cheap. Overseas, Lispro is 20-30 percent more expensive than regular insulin, according to the Dow Jones News Service. Eli Lilly spokesperson Kelly Sego said consumers can expect similarly higher prices in the United States. "It's going to be more expensive, but it is a premium product and it's new," she said.
Why Everyone's so Excited-the Benefits
"The stuff is great" said Ken Gosselin, who has been using Lispro as part of Eli Lilly's clinical trials since 1992, making him one of the drug's first users. "In my opinion, Lispro deserves a seat among the great historical events of diabetes research... It's the closest thing to a cure that can fit into a syringe."
Is such enthusiasm warranted? Many think so. "The benefits of Lispro are several," said Dr. Daniel Einhorn, a San Diego endocrinologist and Diabetes Health board member who oversaw the use of Lispro during its research phase. Convenience is one thing, but what Lispro really has to offer is greater blood sugar control and a reduced risk of hypoglycemia, say patients and physicians.
As Dr. Einhorn explained, much of hypoglycemia stems from the fact that regular insulin lasts for six to eight hours after being injected. If no food has been eaten and there is active R insulin circulating, patients could suffer a hypo. "This is much longer than most individuals recognize or can plan for," he said. With Lispro, most of its blood glucose lowering effect is gone within two hours, making it a more predictable drug.
"What I liked especially about Humalog is that it has removed the fear of hypoglycemia," Gosselin said. He considers himself one of the lucky ones. Participants in the Lilly study, unlike others, were allowed to continue taking Lispro after the trial ended. Friends have been hounding Gosselin to slip them a bottle of Lispro-a temptation he said he's resisted.
"The best two words that I can use to describe its effects are `predictability' and `control'," Gosselin said. During his testimony to the Food and Drug Administration, he related the story of a woman who had to withdraw from a trial because she chose to become pregnant. "I remember her crying when her control deteriorated because she had to return to a regular insulin regimen." Another woman, he said, "with type II diabetes...expressed her profound frustration because of the loss of good control when she had to return to regular insulin as part of the study's protocol."
Does Lispro achieve better control? Two studies presented at the American Diabetes Association's 56th annual scientific meeting in June addressed just this question. Both studies, one conducted by D. Pacaud, the other by R. Rowe, concluded that post-meal glucose levels were better in patients using Lispro, compared to those with regular insulin. But Rowe's study also found that people using Lispro had higher BGs before meals than those using regular insulin.
Studies aside, personal experience is what really counts for most patients. "In my opinion, Lispro is a superb improvement in insulin technology because it seems to closely match the blood sugar effects of most foods I eat. This has meant better after-meal blood sugars, essentially no after-meal hypoglycemia, five pounds of weight loss and improved ability to predict and control my blood sugars," Gosselin said.
A group that will especially benefit from Lispro, noted Dr. Einhorn, are insulin pump users. "The rapid onset of action, the rapid offset of action and therefore the greater predictability of Lispro should make pumping a far more satisfying experience," he said.
Compared to human regular insulin, Lispro was shown to help lower HbA1C levels in pump users, according to a study by B. Zinman presented at the June ADA meeting. The average HbA1C level was 7.65 percent for the 30 type I patients involved in the three-month trial, compared to 7.99 percent for the same people when they were taking human regular insulin.
A Cure in a Syringe?
Not so fast. As with any new drug, especially those made by genetic engineering, questions have been raised about Lispro's risks. Is it safe? Has it been tested on a broad enough segment of the population?
Scott R. King, a medical entrepreneur with diabetes (not to be confused with the Diabetes Health publisher, also named Scott King), is one such cautious observer of Lispro's emergence on the market. "My concern is really about safety. I'm speaking as a scientist who worries about the potential side-effects of changing the structure of insulin," said King, who has a masters degree in biochemistry from Harvard University. When engineers tinker with the structure of the human insulin molecule, he reasons, they run the risk of creating a structure that could imitate the action of other natural hormones within the body.
"To me, there's nothing wrong with waiting 30 minutes before you eat," King said. What's important when considering the value of Lispro is "that the benefit must be larger than the risk."
Genetic fiddling is what makes Steven Lazarus, a New York businessman with diabetes, a bit wary also. "Lispro will prove to be interesting, but I'm not so eager to try it. I want somebody else to be the guinea pig," Lazarus said. Because Lispro is neither animal nor human in origin, like other available insulins, he wonders if it's not more akin to alien insulin.
"Alien insulin?" questions Dr. Nancy Bohannon, who has overseen 75 patients in a number of Lispro trials. "Pork insulin and beef insulin are far more alien because they actually have different amino acids...whereas Humalog has exactly the same amino acids (as human insulin). The only difference is that the 28th and 29th amino acid on the B chain (of the human insulin molecule) are in the reverse order."
Gosselin, a true proponent of Lispro, also attests to its safety. "Anytime you're using a product that God did not make there's a degree of nervousness, there's naturally a concern," admits Gosselin. Years of trials, assurances from physicians and his own investigation of Lispro convinced him that the new insulin was safe. So safe, he said, he feels "more comfortable using Humalog than Nutrasweet."
Eli Lilly conducted trials in 19 countries, involving 3,000 patients over a five year period, according to Sego, Lilly spokesperson, who said the Lispro trials were just as long and extensive as those for most other drugs submitted for FDA approval.
Still, there are those that say more trials are warranted. They want to see research involving a broader subset of people. How Lispro works in the bodies of those who smoke or are pregnant has not been determined, according to an information packet for Humalog supplied by Eli Lilly Sego defended the extensiveness of the trials, saying that they involved young and old alike, "people from two to 85 years old, type Is, type IIs, men and women of various races. It's been an extensive trial done over a long period of time."
Hypoglycemia? Hyperglycemia? Lispro is Strong Stuff
Like Jenny Hirst, Dr. Matthew Kiln, a London physician with diabetes, is also concerned about hypoglycemia and Lispro. His fear is that people with diabetes often eat high-fiber diets, which slows the absorption of carbohydrates. With such a fast-acting insulin, "you can go quite profoundly hypo when you eat slowly absorbed foods," Kiln said.
Hypoglycemic episodes should not be a primary concern when using Lispro, according to Dr. Bohannon. Unless they suffer from hypoglycemia unawareness, people using the new insulin will have enough time to recognize and treat falling blood sugars. "I don't think this is a major problem," she said, noting that this was not an issue for her patients.
Except for one.
Of her 75 patients who took Lispro, only one really disliked the new insulin, Bohannon said. "He was a man who dawdled over eating, he would take at least an hour for one meal," she said. "He ate so slowly that he would end up getting hypoglycemic in the middle of the meal because of the rapid-acting insulin. He just did not get enough carbohydrate in quickly enough and the insulin would beat him to the punch. So if you have somebody who eats extremely slowly, that person would not be a good candidate for Humalog."
Not only can BGs fall fast, but they can rise quickly too, if Lispro is not taken as part of a regimen that includes long-acting insulins like NPH, Lente or Ultralente. "Since Lispro disappears from the bloodstream within such a short time, a person can be left with no insulin at all between meals...This potential disadvantage is fully nullified when longer acting insulins are taken appropriately with Lispro," Dr. Einhorn said.
Patients using Lispro with pumps must be especially careful, he said, since they would have less time to respond if their pump jammed or the battery died. The chance of suffering from diabetic ketoacidosis is more pronounced if the infusion set becomes dislodged when such a fast-acting insulin is used.
Lispro is not a drug to be taken lightly. Using it will involve changes in people's insulin regimens, not only in terms of which insulins they take, but also how much for each injection. Any kind of drastic change in a patient's insulin therapy makes physicians and educators nervous. "Those changes in regimen are always fraught with potential for hyper- and hypoglycemia and so extra care will need to be taken, clearly," Dr. Einhorn said.
Patients involved in the Lispro trials say they had no trouble with hypoglycemia. "I must say I can recommend it," said Ron McAlpine, a 54-year-old Scottish man who has taken Lispro for two years. He takes three injections of Lispro and one injection of a long-acting insulin each day. "I was a bit wary at first, but (Lispro has) never affected me at all," he said.
Lispro-Not for Everyone
"People who view this as a panacea for their diabetic control will be disappointed," Dr. Einhorn said. As convenient as it may be, Lispro is not for everyone. Those who do not want to take more shots and those who are already under good control may not benefit from a switch to Lispro.
Patients who "might not be ideal candidates would be people who graze, who eat a little bit all day and never eat really big meals," Dr. Bohannon said. Since Lispro is designed to be injected right before eating, those who like to eat more than three times per day would have to take more shots to cover those snacks.
For this reason, Dr. Bohannon is pleased to see that Lispro will only be available with a prescription, unlike other, older insulins. Everyone agrees-this is a drug that must be given with education and lots of it. "One of my greatest fears was that someone was going to walk into a pharmacy and say, `I want some of that new insulin, I've heard it's so great,' and without any education at all, they go home and shoot it up before going out to dinner. Then they get in the car to drive to the restaurant, become hypoglycemic and have a horrible accident killing ten innocent people because they had not been adequately educated," Dr. Bohannon said.
Lispro's impact promises to be major. Physicians envision most of America's 700,000 type I people with diabetes using it sometime in the future. As people gain more experience with it, Dr. Bohannon anticipates that at least some of patients' regular insulin will be replaced with Lispro. "Probably in the first year, maybe five or ten percent," of type Is will be using Lispro. "But by five years out, most people will probably be on it at least part of the time," she said.