Diabetic Drug Taken Once Weekly Provides Sustained Glucose Control

Jacquelyn K Beals, PhD

June 10, 2008

June 10, 2008 (San Francisco) — A new study has shown that exenatide taken in a once-weekly (QW) preparation produces better HbA1c and fasting plasma glucose (FPG) levels in patients with type 2 diabetes than when the drug is taken twice daily (BID).

The study was presented here at the Late Breaking Clinical Studies section of the American Diabetes Association 68th Scientific Sessions by John B. Buse, MD, PhD, CDE, president, Medicine & Science, of the American Diabetes Association.

Dr. Buse is also director of the Diabetes Care Center and chief of the Endocrinology Division of the Department of Medicine at the University of North Carolina School of Medicine in Chapel Hill.

Exenatide is an "incretin mimetic" — a drug that mimics the action of naturally occurring hormones such as glucagon-like peptide-1 (GLP-1) that regulate blood glucose by stimulating insulin-dependent glucose secretion, inhibiting glucagon secretion, and slowing gastric emptying. Exenatide is commonly administered BID.

QW administration of exenatide required a new drug formulation. The drug is now combined with "the same stuff that's used to make resorbable sutures," Dr. Buse told Medscape Diabetes & Endocrinology. "So this resorbable suture material apparently forms these beadlike things that have drug in the matrix, and then the bead sort of breaks apart. It's resorbed and the drug is released." The drug is given once a week, but drug release occurs over a period of weeks or months.

Part 1 of the study enrolled 295 patients with type 2 diabetes who were randomly assigned to 1 of 2 treatment groups for 30 weeks. Patients in 1 group were treated with the QW preparation of exetanide; patients in the other group received exetanide BID.

HbA1c decreased more in patients receiving the drug QW than in patients receiving the drug BID (decreasing 1.9% and 1.5%, respectively, from a mean baseline HbA1c of 8.3%). The QW group also showed a greater reduction of fasting plasma glucose (FPG) (−42 compared with −25 mg/dL; mean baseline FPG was 169 mg/dL). At the end of 30 weeks, patients in each group had lost approximately 4 kg.

An additional 22-week study was completed by 241 patients. Half of these patients (n = 120) continued to receive exetanide QW; the other half (n = 121) were switched from receiving exetanide BID to receiving the drug QW. Patients who received exetanide QW for the entire 52-week study showed an average HbA1c decrease of 2.0% and an average FPG reduction of 47 mg/dL. Patients who changed from exetanide BID to exetanide QW attained similar reductions (2.0% and 43 mg/dL).

Patients in both groups had similar weight loss. Dr. Buse noted in his presentation: "In the patients who did not lose weight, the reduction in HbA1c was less, but it was still quite substantial, about 1.5% or so.... The heavier patients did lose a bit more weight than the less heavy patients, so the weight loss is proportional to the total degree of obesity, though basically all groups lose weight."

"Clinically significant" decreases in blood pressure were observed in both groups of patients: There was a mean decrease in systolic pressure of 5.7 mm Hg (QW) compared with 4.0 mm Hg (BID/QW), and a mean decrease in diastolic pressure of 2.2 mm Hg (QW) compared with 2.1 mm Hg (BID/QW) by the end of the 52-week study.

Nausea was reported in approximately 7% of the patients. "One of the nice things about this long-acting formulation is that the levels of exenatide, as the capsular material dissolves, increase relatively slowly," said Dr. Buse. "So in general, it is better tolerated than the exenatide twice a day. There are some patients who have nausea, but it tends not to be severe nausea or consistent nausea all day every day."

Medscape Diabetes & Endocrinology also talked via email with the chair of the Late Breaking Clinical Studies section, Anne L. Peters, MD, CDE, who is director of the Clinical Diabetes Programs at the University of Southern California and professor of clinical medicine at the university's Keck School of Medicine. Dr. Peters noted that this study showed "the longer-term benefit to a QW preparation of exenatide. It also illustrated the rapid increase and subsequent decrease in plasma glucose levels that occurs when switching from BID to QW therapy." The latter fact is one "that patients and providers will need to be aware of when transitioning from one preparation to the other," Dr. Peters said.

Dr. Buse reported that he is a consultant for Merck & Co, Inc; sanofi-aventis; and Roche Diagnostics Corporation and is a member of the speakers bureau for Colgate. He holds stock/shares in Insulet. Dr. Peters reported that she has received research support from Abbott Laboratories.

American Diabetes Association 68th Scientific Sessions: Late Breaking Clinical Studies. Presented June 9, 2008.

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