WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca today announced results from a 10-week randomized, controlled, double-blind, Phase IV study investigating the quality of glucose control with BYDUREON® (exenatide extended-release) for injectable suspension versus placebo using continuous glucose monitoring (CGM) in patients with type 2 diabetes uncontrolled on metformin. The results were presented in a poster presentation (#1014-P) at the 76th Scientific Sessions of the American Diabetes Association (ADA) in New Orleans.
The study randomized 117 patients to BYDUREON (n=61) or placebo (n=56) and included a four-week lead-in period, 10-week treatment period and four-week follow-up for standard safety assessments. Glucose concentrations were measured every five minutes over seven days during the final week (baseline) of the four-week lead-in period and during weeks four and 10 using a CGM system. Study participants also received dietary and exercise counseling and were instructed on medical nutrition in accordance with the American Diabetes Association guidelines or locally accepted guidelines.1
In the study, patients receiving BYDUREON showed significant improvements in overall 24-hour glucose control and reduced glucose fluctuations as early as week four. The study met its primary endpoint of change from baseline in 24-hour mean weighted glucose. BYDUREON plus metformin significantly (P<0.001) reduced 24-hour mean weighted glucose from baseline to week four (−26 mg/dL) and week 10 (−31 mg/dL) compared with placebo plus metformin. BYDUREON significantly (P<0.001) improved secondary endpoints of fasting plasma glucose (−30 mg/dL; −42 mg/dL) and postprandial glucose (−32 mg/dL; −44 mg/dL at week four and at week 10).1
For assessments of glucose fluctuation, BYDUREON resulted in a significantly (P<0.001) greater reduction in mean amplitude of glucose excursions versus placebo at week 10 (−15.2 mg/dL). Glycemic control was consistent, as shown by no difference in 24-hour mean weighted glucose from day 1 to day 6 of week 10. BYDUREON increased time in the euglycemic range (53% at baseline to 77% at week 10). Despite decreasing the time spent in the hyperglycemic range as early as week 4 (47% at baseline to 22% at week 10), BYDUREON did not increase the time spent in the hypoglycemic range at 4 and 10 weeks.1
Jim McDermott, Head of Medical, US Medical Affairs, Diabetes, AstraZeneca, said: “In this study, after four and 10 weeks of treatment, BYDUREON produced significant, clinically meaningful changes in glycemic control and resulted in more time in the euglycemic, or normal, range without significantly more time in the hyper- or hypoglycemic range1 – an important measure for patients and healthcare practitioners. Due to its unique delivery system and if used as directed, BYDUREON plasma concentrations never trough, which means patients and healthcare practitioners can be confident that the treatment can help make a difference.”
The most common (≥5%) adverse events (AEs) were mild injection-site nodule (BYDUREON, 10.0%; placebo, 0.0%), mild-to-moderate nausea (respectively 6.7% and 0.0%), mild-to-moderate urinary tract infection (respectively 6.7% and 8.9%), diarrhea (respectively 5.0% and 3.6%), hematuria (respectively 5.0% and 0.0%), injection site induration (respectively 5.0% and 5.4%), musculoskeletal pain (respectively 5.0% and 0.0%) and proteinuria (respectively 5.0% and 1.8%).1
Paul Jellinger, MD, endocrinologist at Memorial Regional Hospital in Fort Lauderdale, FL, said: “As clinicians, we often evaluate type 2 diabetes control by measuring A1C, which reflects blood glucose over two to three months; however, this approach does not reveal intra-day blood sugar excursions. Measuring continuous glucose levels provides an important way to look at both glycemic control and undetected excessive glycemic fluctuations not evident from an A1C determination. Data from this study showed significant reduction of glucose fluctuations with exenatide extended-release as early as four weeks into treatment.1”
Further exploratory analysis of BYDUREON and glucose fluctuations was provided in the poster “Effects of Exenatide Once Weekly on Dynamics of 24h Glucose Patterns in Patients with T2D” (#1048-P).2
Indication and Important Limitations of Use for BYDUREON® (exenatide extended-release) for injectable suspension
BYDUREON is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- BYDUREON is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of the rat thyroid C-cell tumor findings to humans. Prescribe only to patients for whom potential benefits are considered to outweigh potential risk.
- Not a substitute for insulin, should not be used in patients with type 1 diabetes or diabetic ketoacidosis, and cannot be recommended for use with insulin.
- BYDUREON and BYETTA® (exenatide) injection both contain the same active ingredient, exenatide, and should not be used together.
- Exenatide has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, based on postmarketing data. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using BYDUREON; consider other antidiabetic therapies for these patients.
Important Safety Information for BYDUREON® (exenatide extended-release) for injectable suspension
WARNING: RISK OF THYROID C-CELL TUMORS
- Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of exenatide extended-release-induced rodent thyroid C-cell tumors has not been determined.
- BYDUREON is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of BYDUREON and inform them of symptoms of thyroid tumors (e.g., mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for detection of MTC in patients treated with BYDUREON.
- Patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- Patients with prior serious hypersensitivity reactions to exenatide or to any of the product components.
Warnings and Precautions
- Pancreatitis: Based on postmarketing data, exenatide has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. After initiation of BYDUREON, observe patients carefully for pancreatitis (persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting). If pancreatitis is suspected, BYDUREON should be discontinued promptly and should not be restarted if pancreatitis is confirmed.
- Increased Risk of Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin: Consider reducing the insulin secretagogues (e.g., sulfonylureas) or insulin dose to reduce the risk of hypoglycemia.
- Renal Impairment: Should not be used in patients with severe renal impairment or end-stage renal disease. Use with caution in patients with renal transplantation or moderate renal failure. Postmarketing reports of altered renal function with exenatide, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation.
- Gastrointestinal Disease: Because exenatide is commonly associated with gastrointestinal adverse reactions, BYDUREON is not recommended in patients with severe gastrointestinal disease (eg, gastroparesis).
- Immunogenicity: Patients may develop antibodies to exenatide. In 5 registration trials, attenuated glycemic response was associated in 6% of BYDUREON-treated patients with antibody formation. If worsening of or failure to achieve adequate glycemic control occurs, consider alternative antidiabetic therapy.
- Hypersensitivity: Postmarketing reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema). If this occurs, patients should discontinue BYDUREON and other suspect medications and promptly seek medical advice.
- Injection-Site Reactions: Postmarketing reports of serious injection-site reactions (eg, abscess, cellulitis, and necrosis), with or without subcutaneous nodules, with the use of BYDUREON.
- Macrovascular Outcomes: No clinical studies establishing conclusive evidence of macrovascular risk reduction with BYDUREON or any other antidiabetic drug.
- The most common (≥5%) adverse reactions reported in BYDUREON-treated patients and occurring more frequently than comparator in clinical trials were nausea (16.9%), diarrhea (12.7%), headache (8.0%), vomiting (6.8%), constipation (5.9%), injection-site pruritus (5.9%), injection-site nodule (5.3%), and dyspepsia (5.1%).
- Oral Medications: BYDUREON slows gastric emptying and can reduce the rate of absorption of orally administered drugs. Use with caution with oral medications.
- Warfarin: Postmarketing reports with exenatide of increased international normalized ratio (INR) sometimes associated with bleeding with concomitant use of warfarin. Monitor INR frequently until stable upon initiation or alteration of BYDUREON.
Use in Specific Populations
- Pregnant and Nursing Women: Based on animal data, BYDUREON may cause fetal harm and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. To report drug exposure during pregnancy call 1-800-633-9081. When administered to a nursing woman, a decision should be made whether to discontinue nursing or to discontinue BYDUREON.
- Pediatric Patients: Use in pediatric patients is not recommended as safety and effectiveness have not been established.
NOTES TO EDITORS
About Type 2 Diabetes
Diabetes is estimated to affect 29.1 million people in the US3 and 415 million people worldwide.4 Type 2 diabetes accounts for approximately 90-95 percent of adults diagnosed with diabetes in the US.3 The prevalence of diabetes is projected to reach more than 642 million people worldwide by 2040.4 Type 2 diabetes is a chronic and progressive disease characterized by multiple pathophysiologic defects leading to elevated glucose levels.4,5 Significant unmet needs still exist, as many patients remain inadequately controlled on their current glucose-lowering regimen.6 It is estimated that nearly half of people living with type 2 diabetes are not achieving recommended A1C goals based on guidelines established by professional societies and advocacy organizations for diabetes management.7
About AstraZeneca in Diabetes
AstraZeneca is pushing the boundaries of science with the goal of developing life-changing medicines that aim to reduce the global burden and complications of diabetes. Our current portfolio consists of the three newest classes of non-insulin, anti-diabetic treatments that support individualized treatment approaches: SGLT-2 inhibitors, GLP-1 receptor agonists and DPP-4 inhibitors.
As a strategic therapy area for the company, we are focusing our research and development efforts on diverse populations and patients with significant co-morbidities, such as cardiovascular disease, obesity, non-alcoholic steatohepatitis (NASH), and chronic kidney disease.
Our commitment to diabetes is exemplified by the depth and breadth of our global clinical research program. This commitment is advancing understanding of the treatment effects of our diabetes medicines in broad patient populations, as well as exploring combination treatment approaches to help more patients achieve treatment success earlier in their disease progression. Our ambition is to reduce the long-term impact of diabetes.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas – respiratory, inflammation, autoimmune disease (RIA), cardiovascular and metabolic disease (CVMD) and oncology – as well as in infection and neuroscience. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca-us.com.
1 Frías JP, Ruggles JA, Zhuplatov S et al. Effect of Exenatide Once Weekly on Glycemic Fluctuations in Patients With Type 2 Diabetes. American Diabetes Association Scientific Sessions 2016. Abstract #1014-P.
2 Strange P, Ruggles JA, Zhuplatov S et al. Effects of Exenatide Once Weekly on Dynamics of 24-h Glucose Patterns in Patients With Type 2 Diabetes. American Diabetes Association Scientific Sessions 2016. Abstract #1048-P.
3 Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014. Atlanta, GA: US Department of Health and Human Services; 2014.
4 International Diabetes Federation. IDF Diabetes Atlas, 7th ed. Brussels, Belgium: International Diabetes Federation; 2015. http://www.idf.org/diabetesatlas. Accessed January 26, 2016.
5 Defonzo RA. From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus. Diabetes. 2009;58:773-795.
6 Wong ND, Patao C, Wong K, et al. Trends in control of cardiovascular risk factors among US adults with type 2 diabetes from 1999 to 2010: comparison by prevalent cardiovascular disease status. Diab Vasc Dis Res. 2013;10:505-513.
7 American Diabetes Association. Diabetes Care. 2016;39(suppl 1):S1-S112.