Applied Evidence

Diabetes drug update: How 4 new options stack up

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3 new agents and a new delivery system for insulin.


 

References

Practice recommendation
  • Inhaled insulin, a short-acting insulin for type 1 and type 2 diabetes, is comparable with traditional subcutaneous regimens in terms of hemoglobin A1c and postprandial glucose reductions. It can also reduce the number of daily injections (B).
  • Exenatide, which is indicated for type 2 diabetes in those uncontrolled on a sulfonylurea or metformin, provides a modest reduction in A1c and fasting glucose and is best suited for those whose A1c is within 1% of their goal. Among its advantages: weight loss and the potential to slow the progression of the disease (B).
  • Sitagliptin is indicated for type 2 diabetes alone or in combination with metformin or a thiazolidinedione. It provides A1c reductions that are comparable to exenatide and does not have high rates of gastrointestinal side effects. It may also improve beta-cell function (B).
  • Pramlintide, which is indicated for type 1 or type 2 diabetes uncontrolled with mealtime insulin, provides modest reductions in A1c and postprandial glucose—although it's more effective for those with postprandial hyperglycemia. It may reduce insulin dose requirements and the associated weight gain (B).

Strength of recommendation (SOR)

  1. Good quality patient-oriented evidence
  2. Inconsistent or limited-quality patient-oriented evidence
  3. Consensus, usual practice, opinion, disease-oriented evidence, case series

The battle over glycemic control begins when you write out that first script for a patient for a sulfonylurea, metformin, or insulin. But it continues during every encounter thereafter, as you monitor your patient's progress, adjust dosages, and take advantage of new pharmacologic options. Recently, that list of options has expanded by 4: Three are new classes of agents, and the fourth is essentially a new delivery system for insulin. Inhaled insulin (Exubera) was approved by the Food and Drug Administration in January 2006, exenatide (Byetta) in April 2005, sitagliptin (Januvia) in October 2006, and pramlintide (Symlin) in March 2005 ( TABLE 1 ).

Staying abreast of new agents like these is essential if we are ever going to get the upper hand on a disease that in 2002 affected 18.2 million people.1 This review provides an at-a-glance summary of the key aspects of each agent, followed by a topline summary of their advantages and disadvantages.

TABLE 1
New therapeutic options for diabetes

DRUGINDICATIONSDOSECOST (AWP)*
Insulin, inhaled powder (Exubera)Type 1 or type 2 diabetes mellitusAdminister 2-3 times a day just prior to meals. Dose (mg)=weight (kg)×0.05 mg/kg. Calculated dose should be rounded down to nearest whole milligramKit (includes inhaler plus 270 1- and 3-mg doses): $180 combination pack (180 1- and 3-mg doses): $134 combination pack (270 1- and 3-mg doses): $168
Exenatide (Byetta)Adjunct therapy for type 2 diabetes uncontrolled with metformin or sulfonylureaInitial: 5 mcg sc twice daily. May be increased to 10 mcg sc twice daily after 1 month (max dose)5 mcg: $176.40/month
10 mcg: $207.00/month
Sitagliptin (Januvia)Type 2 diabetes as monotherapy or in combination with metformin or thiazolidinedione100 mg orally once daily$174.96/month
Pramlintide (Symlin)Adjunct therapy for type 1 or type 2 diabetes in uncontrolled patients using mealtime insulin (with or without sulfonylurea or metformin in type 2 diabetes)Type 1 diabetes:
Initial: 15 mcg sc prior to each meal.
Titrate to 30-60 mcg prior to each meal as tolerated.
Type 2 diabetes:
Initial: 60 mcg sc prior to each meal.
Titrate to 120 mcg sc prior to each meal.
$95.40/month
AWP=average wholesale price; sc=subcutaneously
*Cost from Red Book Update 2006; 25(9) (Montvale, NJ: Thomson PDR; 2006).

Exubera: A new twist on insulin

The first dry powder inhaled insulin, which can be used in lieu of rapid- or short-acting injectable insulins, is now available. The question is: How does it stack up? Inhaled insulin has been studied in several clinical trials in both type 1 and type 2 diabetes ( TABLE 2 ).2-8 In type 1 diabetes it's been combined with NPH insulin or ultralente insulin and compared with subcutaneous regimens of regular insulin with NPH insulin or ultralente insulin.2,3,6 These studies showed a similar decrease in glycosylated hemoglobin (Hb A1c) and 2-hour postprandial glucose between the inhaled and subcutaneous regimens. No studies comparing inhaled insulin powder containing regimens with subcutaneous regimens utilizing rapid acting insulin have been published.

In type 2 diabetes, inhaled insulin powder has been studied in combination with ultralente insulin, a sulfonylurea, and metformin.4,5,7,8 For patients with uncontrolled type 2 diabetes on a sulfonylurea or metformin, the addition of inhaled insulin powder has been shown to reduce A1c by 1.9% to 2.3%.4,8 When combined with ultralente in type 2 diabetes, reductions in A1c were comparable with traditional subcutaneous insulin regimens.

In addition, a few studies have looked at patient satisfaction with inhaled insulin. The findings: Inhaled insulin powder was linked to better satisfaction, convenience, ease of use, and social comfort in type 1 and 2 diabetes when compared to entirely subcutaneous regimens.6,9,10

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