Evaluation of Exenatide in Patients With Diabetic Neuropathy

Not Applicable

Completed

Brief Summary: This study will look at whether or not the medication exenatide improves signs and symptoms of diabetic peripheral neuropathy in people with type 2 diabetes and mild to moderate diabetic peripheral neuropathy.

Detailed Description: This study will look at the effects of the medication exenatide on peripheral neuropathy in people with type 2 diabetes. Exenatide (trade name, BYETTA®) is an injectable medication used by people with type 2 diabetes to control blood sugar. Peripheral neuropathy is a complication of diabetes that can cause symptoms such as numbness, tingling or burning sensations in the feet and hands. Controlling blood sugars levels in type 2 diabetes is thought to prevent, delay or improve the damage to the nerve fibers that causes peripheral neuropathy. There is also some evidence that exenatide may have additional beneficial effects on the peripheral nerves, beyond the benefits of blood sugar control alone. In this study, about half of the participants will take exenatide by injection twice daily and the other half will take insulin glargine (Lantus®) by injection once daily. Both groups are expected to have similar improvement in blood sugar control. This study will show whether exenatide has beneficial effects on neuropathy beyond the benefits of better blood sugar control alone.

Recruitment & Eligibility

Inclusion Criteria

Type 2 diabetes treated with one or more oral agents
Persistent fasting glucose > 140 mg/dl or HbA1c > 7%
Stable and maximally effective doses of one or more oral agents for 3 months
Presence of diabetic peripheral neuropathy
Age between 18 and 70 years
No risk factors or other causes of neuropathy
Willingness and capacity to sign the Institutional Review Board approved consent form and cooperate with the medical procedures for study duration

Exclusion Criteria

Nursing mothers or pregnant women
A history of previous kidney, pancreas or cardiac transplantation
A past history of neuropathy (independent of diabetes) or with a disease known to be associated with neuropathy (e.g., hepatitis C, end stage renal disease, lupus)
Amputation of any part of either lower extremity for any reason or traumatic loss of any part of either lower extremity or congenital absence or severe deformity of lower extremity
HbA1c > 10%
Participation in an experimental medication trial within 3 months of starting the study.
Undergoing therapy for malignant disease other than basal- or squamous cell carcinoma
Requiring long-term glucocorticoid therapy
Inability or unwillingness to comply with the protocol

Arm && Interventions

Group	Intervention	Description
glargine	Glargine	Subjects will take 1 daily injection of insulin glargine for 18 months.
Exenatide	Exenatide	Subjects will take exenatide by subcutaneous injection twice daily for 18 months

Primary Outcome Measures

Name	Time	Method
Confirmed Clinical Neuropathy (CCN)	18 Months	CCN was defined by a composite score comprised of at least two positive responses among symptoms, sensory signs, or absent or hypoactive reflexes consistent with a distal symmetrical polyneuropathy (16), and at least one abnormal nerve conduction study result in two anatomically distinct nerves, e.g. the sural sensory and peroneal motor nerves (defined as a amplitude \< 5 μV and a conduction velocity \< 40 m/sec for the sural nerve and an amplitude \< 2.5 μV and a conduction velocity \< 40 m/sec for the peroneal nerve).

Secondary Outcome Measures

Name	Time	Method
Cardiac Autonomic Neuropathy (CAN)	18 months	Group differences in E/I ratio, a measure of cardiac autonomic function.
Cardiac Autonomic Neuropathy	18 month	resting heart rate as marker of autonomic function at rest