In 1998, Eli Lilly & Co.’s rapid-acting insulin analogue lispro (Humalog) appeared on the U.S. market, followed in 2000 by Novo Nordisk’s rapid-acting counterpart aspart (NovoLog). Joined now by sanofi-aventis’ glulisine (Apidra), these rapid-acting insulins offer both convenience and improved blood glucose control to people who require bolus insulin.
Sanofi-aventis’ glargine (Lantus), the first commercial long-acting insulin analogue, has facilitated better basal insulin coverage for millions of patients with both type 1 and type 2 diabetes since its introduction in 2000. And now Novo Nordisk’s insulin detemir (Levemir) presents another new option for basal insulin therapy.
As insulin analogues are moving from the cutting edge to the mainstream, what are professionals and patients to do?
“The challenge for the prescribing physician is to recognize the state of diabetes and whether the patient can respond to a basal insulin alone, or whether the patient needs both a basal insulin and a bolus component,” says Alan Moses, MD, medical director for Novo Nordisk Pharmaceuticals. “Clinical trial data suggest that when the A1C is above 8.5% to 9%, it is more likely that the patient will respond better to basal-bolus treatment, although the primary goal is to get the blood glucose levels down to as low as can be achieved safely.”
The Three Rapid-Acting Insulin Analogues
Humalog, NovoLog and Apidra begin working within about 15 minutes of bolus, peak 60 to 90 minutes later and have a duration of therapeutic activity of approximately four hours. Rapid-acting analogues are essentially equal in terms of pharmacodynamics and pharmacokinetics.
Patients on multiple daily injections of insulin may prefer one analogue over another in part because of the corresponding injection pen. Sanofi-aventis’ recently revamped OptiClik injection pen can be used with Apidra, which may pique the interest of patients already accustomed to using the device to inject Lantus.
“The Apidra cartridge for use in OptiClik is an important addition to the sanofi-aventis portfolio of diabetes treatments,” says Poul Strange, vice president of medical affairs, diabetes, at sanofi-aventis. “We can now offer physicians and patients both the number-one prescribed insulin, the once-daily 24-hour basal insulin Lantus, as well as Apidra—a novel mealtime insulin developed for flexible use. When taken together, these two products will provide a complementary approach to overall glucose control.”
All three rapid-acting analogues are approved for use in insulin pumps.
Intermediate-Acting vs. Long-Acting Analogues
Levemir is an exciting addition to our arsenal of basal insulin options for patients who take insulin. Today most clinical researchers well versed in the insulins commonly used for basal coverage would argue that NPH is not an appropriate basal insulin; its variable intra-patient absorption rate (10 to 55 percent from injection to injection), its pronounced peak and its dose-dependent duration make it a very fearsome beast to tame. It is especially difficult for patients taking NPH to achieve euglycemia overnight, when they are prone to hypoglycemia because of naturally greater insulin sensitivity at night and because a delayed hypo resulting from physical activity or alcohol consumption during the evening may coincide with the “peaking” of the evening NPH dose.
Lantus is currently the most-prescribed prescription insulin product that is a once-daily, 24-hour, long-acting basal insulin with no pronounced peak. Levemir may help many patients who have not achieved optimal control on Lantus and for whom insulin pump therapy is not indicated.
Finding the Right Regimen
Ultimately, the right insulin regimen for patients with diabetes is the one that is tailored to your lifestyle and preferences. Insulin analogues can bring flexibility and convenience to diabetes management as well as reduced hyper- and hypoglycemia. After generations of altering their lifestyles to fit their diabetes care regimen, today’s insulin users and their care teams can design regimens that enable patients to reach their career, academic, fitness and personal goals without sacrificing the pursuit of euglycemia.
Long-Acting Levemir Now Available
With the FDA approval of its long-acting insulin Levemir (insulin detemir [rDNA origin] injection), Novo Nordisk, Inc., became the second company (sanofi-aventis is the other) with both a rapid- and long-acting insulin. Novo Nordisk, however, is the first company marketing a full portfolio of insulin analogues—rapid-acting, long-acting and pre-mixed.
On March 28, 2006, Novo Nordisk announced that Levemir is now commercially available in the United States.
“Levemir is indicated for once- or twice-daily injection for the treatment of adults and children with type 1 diabetes and adults with type 2 diabetes,” says Novo Nordisk. “The relatively flat action profile of Levemir offers patients up to 24 hours of effective blood glucose control.”
In an interview with Diabetes Health, Peter Aurup, MD, vice president of clinical development, medical, and regulatory affairs for Novo Nordisk, says, “Clearly, what we want the healthcare professional and patient to do is to individualize treatment. We recommend that you initiate therapy with Levemir once a day, preferably in the evening, at a dose of, say, 10 units. Then you base your subsequent titration on your glycemic response.”
Novo Nordisk adds that in a clinical trial, 70 percent of Levemir patients achieved the target A1C level of less than 7%.
“Importantly, Levemir offers a low rate of hypoglycemia and is the first insulin to demonstrate consistently less weight gain in 12 out of 12 controlled clinical trials,” says Novo Nordisk.
Levemir is available in vials and the Levemir FlexPen. Full prescribing information for Levemir is available from Novo Nordisk, Inc., or by logging on to www.novonordisk-us.com.
Source: Novo Nordisk, Inc.
- Hypoglycemia is the most common adverse effect of all insulin therapies, including Levemir. As with all insulins, the timing of hypoglycemic events may differ among various insulin formulations. Glucose monitoring is recommended for all patients with diabetes.
- Other adverse events commonly associated with insulin therapy may include injection-site reactions (on average, 3 to 4 percent of patients in clinical trials) such as lipodystrophy, redness, pain, itching, hives, swelling or inflammation.
- Any change of insulin dose should be made cautiously and only under medical supervision. Levemir should not be diluted or mixed with any other insulin preparations or used in insulin infusion pumps.
Source: Novo Nordisk, Inc.
Eli Lilly Throws New Insulin Into the ‘Mix’
On February 7, Eli Lilly and Co. launched a new premixed insulin, Humalog Mix50/50 (50 percent insulin lispro protamine suspension, 50 percent insulin lispro injection (rDNA origin).
“Humalog Mix50/50 is for use in patients with diabetes to control high blood sugar and is available in an easy-to-use pen delivery device,” says Eli Lilly in a news release.
“Humalog Mix50/50 is designed to provide blood sugar control between meals but also includes a higher percentage of rapid-acting insulin for people with diabetes who need more insulin control at mealtimes.
For more information, log on to www.lillydiabetes.com.
Source: Eli Lilly & Co.