Byetta as monotherapy

[participant3]

Is there any data to support using Byetta monotherapy in type 2 diabetes? I've had PA requests for new members who are just on Byetta.

[chantell.reagan]

Byetta is currently only indicated for use in Type 2 diabetes as adjunctive therapy.

However, two studies evaluated the safety and efficacy of exenatide as first-line monotherapy:

• The first study was published in 2007 in Diabetes Technology and Therapeutics. In an open-label extension phase, 127 patients treated with metformin or diet and exercise were given exenatide (5 mcg BID for 4 weeks, followed by 10 mcg BID for 26 weeks). Exenatide monotherapy and combination therapy with metformin were associated with similar reductions in A1C (1% reduction and 0.9% reduction, respectively). Both treatments also resulted in similar weight decreases. Authors concluded that exenatide monotherapy resulted in glycemic improvements similar to those of exenatide combination therapy with metformin.
• The second study was published in August 2008 in Clinical Therapeutics. This was a 24-week, double-blind, placebo-controlled, parallel-group study in 232 treatment-naïve patients. Treatment with 5 and 10 mcg of exenatide BID was associated with reductions in A1C by 0.7% and 0.9%, respectively, from an average baseline A1C of 7.8%. Significant reductions were also noted in fasting serum glucose and postprandial glucose excursions. At study endpoint, approximately 60% of patients had an A1C of 7% or less. Additionally, weight reduction, beta-cell function (HOMA-B), and improved blood pressure were also seen in the exenatide groups. Authors concluded that exenatide is safe and effective and can be a viable option in the treatment of diabetes as first-line monotherapy.

At this point, it is unclear whether in the future Byetta will be indicated for use as monotherapy.

Of note, according to the ADA guidelines, it is expected that exenatide should produce a 0.5-1% reduction in A1C. It should be also noted that metformin monotherapy is expected to have a possibly greater impact of 1.5% reduction in A1C. Therefore, in treatment-naïve patients, metformin monotherapy might be a more cost-effective option.

Sources:

ADA. Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy. Diabetes Care. 2006;29:1963-1972.

Byetta prescribing information

Safety and Efficacy of Exenatide as Monotherapy (ClinicalTrials.gov)

Moretto TJ et al. Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2008;30:1448-60. Pubmed abstract available

Nelson P et al. The incretin mimetic exenatide as a monotherapy in patients with type 2 diabetes. Diabetes Technol Ther. 2007;9:317-26. Pubmed abstract available

[chantell.reagan]

One of our members offered the following comments:

“Amylin and Eli Lilly are pursuing a monotherapy indication for Byetta in Diabetes mellitus. The PDUFA action date is in February 2009. We normally follow the ADA and AACE guidelines as it relates to recommended treatment. Off-label requests are reviewed on a case-by-case basis and take into consideration peer reviewed published literature (RCT), patient’s concomitant conditions (which may affect selection of drug therapy) and past medical history (which drugs tried, failed; results with each)."

In addition, the 2006 ADA algorithm, Nelson et al, and Moretto et al were also cited as useful references.

[chantell.reagan]

Please see the latest update to the ADA algorithm, issued this week:

ADA. Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy. Diabetes Care. 2008 (abstract only)

[Nochmar]

We require the maximization of oral hypoglycemics before considering Byetta; we also ask that people stay on these meds when placed on Byetta; there are documented advantages in A1c reduction.

[participant1]

I agree with many of these points but we still see cases of Byetta monotherapy in our population.

Is it clinically reasonable to have a patient switched from Januvia (with or without metformin) to Byetta monotherapy?

Also, is there any data that can support the use of Byetta and Januvia as combination therapy?

[chantell.reagan]

There is no contraindication for having a patient who has an inadequate response to Januvia (sitagliptin) to be switched to Byetta (exenatide), particularly if the patient has been on combination therapy with another agent, such as metformin. Evidence from a head-to-head randomized pharmacodynamic cross-over study suggests that Byetta may have greater potency as compared to Januvia, but the impact on the overall clinical benefit is unclear. In addition, Byetta is included in the latest algorithm, provided by the ADA, as a combination therapy with metformin (albeit, this combination is less well-validated then a combination with insulin or a sulfonylurea), whereas the algorithm did not include treatment with DPP-4 inhibitors.

Januvia, either as monotherapy or in combination with metformin, glipizide or pioglitazone, has proven to have a positive effect on parameters of β-cell function and glycemic control in clinical studies. A Medline search did not reveal any studies of combination therapy with Januvia and Byetta. Furthermore, the two current diabetes guidelines ADA 2008 and AACE 2007 do not mention combination therapy with these products. In addition, because both products are considered to be incretin mimetics, hypothetically this combination may not be as synergestic, as compared to combinations that include agents with more diverse mechanisms of action.

Sources:

Hermansen K., Kipnes M., Luo E., et al. Sitagliptin Study 035 Group: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitaliptin, in patients with type 2 diabetes inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab 9. 733-745. 2007.

Rosenstock J., Brazg R., Andryuk P.J., et al: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther 28. (10): 1556-1568. 2006.

Chia CW, Egan JM. Incretin-Based Therapies in Type 2 Diabetes Mellitus. J Clin Endocrinol Metab, October 2008, 93(10):3703–16.

DeFronzo RA, Okerson T, Viswanathan P, et al. Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study. Curr Med Res Opin. 2008 Oct; 24(10):2943-52. Pubmed abstract

Merck Januvia (sitagliptin) prescribing information. Whitehouse Station, NJ; 2008 Oct.