Santarus, Inc. (NASDAQ: SNTS) and VeroScience, LLC today announced publication of a review article and recommendations of an American Association of Clinical Endocrinologists (AACE) expert panel on the role of bromocriptine-QR in the management of type 2 diabetes. The panel concluded that treatment with CYCLOSET ® (bromocriptine mesylate), also referred to as bromocriptine-QR, may be useful in the treatment of patients with type 2 diabetes, both early and late in the life cycle of the disease, and especially for patients with a history of cardiovascular disease or who have significant risk factors for cardiovascular disease. The article, titled The Role of Bromocriptine-QR in the Management of Type 2 Diabetes Expert Panel Recommendations will appear in print form in the January/February issue of Endocrine Practice, a peer-reviewed medical journal published by AACE, and can be found in the online edition of the journal at http://aace.metapress.com/home/main.mpx.
The expert panel also made the following observations and recommendations:
- CYCLOSET has a novel mechanism of action that appears to involve enhancement of morning central nervous system dopaminergic activity, which is reduced in obese individuals with type 2 diabetes. This improvement can potentially lead to improved insulin sensitivity and reduced hepatic glucose output.
- Adjunctive administration of CYCLOSET in the dosing range of 1.6 mg/day to 4.8 mg/day may result in a mean reduction in A1c levels of 0.69% (95% Confidence Interval: 0.97%, 0.41%).
- A 24-week completer analysis performed among efficacy subgroups of patients from the CYCLOSET safety study stratified based on the patient’s baseline A1c levels (≥7.5 to <8.0 versus 8.0 to 8.5 versus ≥8.5).(Vinik et al, Endo. Practice Vol18, p 931-943, 2012) yielded the following results: in the subgroup treated with metformin (with or without another oral hypoglycemic agent), treatment with bromocriptine-QR was associated with a significantly higher proportion of subjects achieving a Week 24 A1c level ≤7 compared with placebo when baseline A1c levels were ≥7.5 to <8.0 or 8.0 to 8.5 (47% versus 4% and 42% versus 6%, respectively). In the subgroup treated with metformin and a sulfonylurea agent, treatment with bromocriptine-QR was also associated with a significantly higher proportion of patients achieving a Week 24 A1c level ≤7 compared with placebo when baseline A1c levels were ≥7.5 to <8.0 or 8.0 to 8.5 (57% versus 5% and 46% versus 8%, respectively).
- Improvement in glycemic control during adjunctive treatment with CYCLOSET is achieved with minimal intrinsic risk of hypoglycemia and without clinically significant adverse effects on weight, triglycerides, free fatty acids or blood pressure.
- The large (n=3,070) placebo-controlled 12-month safety study provides the most detailed and systematic information on the long-term tolerability of CYCLOSET in the treatment of type 2 diabetes. Nausea was the most common adverse event (32.2%), and was associated with premature study discontinuation in 7.6% of patients. Other adverse events occurring with an incidence of at least 10% were dizziness (14.8%), fatigue (13.9%), and headache (11.4%). The incidence of nausea was similar in short-term placebo-controlled trials when CYCLOSET was used as a monotherapy (32.5%) or when it was used as an adjunctive therapy with sulfonylurea (25.4%).
- The major limitation to the use of CYCLOSET is the relatively small clinical trials database. As a result, there is currently insufficient information on the safety and efficacy of adjunctive therapy with CYCLOSET in type 2 diabetes patients being treated with other diabetes regimens such as thiazolidinediones or insulin.
- CYCLOSET’s novel mechanism of action and favorable cardiovascular risk profile may make it a useful addition to the spectrum of agents available to treat type 2 diabetes.
The members of the expert panel were:
- Alan J. Garber, MD, PhD, Departments of Medicine, Biochemistry and Cell Biology, Baylor College of Medicine, Houston, Texas;
- Lawrence Blonde, MD, FACP, FACE, Ochsner Diabetes Clinical Research Unit, Department of Endocrinology, Diabetes and Metabolism, Ochsner Medical Center, New Orleans, Louisiana;
- Zachary T. Bloomgarden, MD, Department of Medicine, Mount Sinai School of Medicine, New York City, New York;
- Yehuda Handelsman, MD, FACP, FACE, Metabolic Institute of America, Tarzana, California; and
- Samuel Dagogo-Jack, MD, Division of Endocrinology, Diabetes and Metabolism and Clinical Research Center, University of Tennessee Health Science Center, Memphis, Tennessee.
Financial support for the AACE expert panel workshop was provided by Santarus through an independent grant. Santarus did not participate in or have any influence on the AACE panel workshop, recommendations or publication.