Continuous Glucose Monitoring Evaluation of Exenatide Twice Daily Versus Insulin Glargine

Not Applicable

Completed

Conditions: Type 2 Diabetes

Interventions: Drug: Exenatide
Drug: Insulin Glargine

Registration Number: NCT01089569

Lead Sponsor: HealthPartners Institute

Brief Summary: The primary purpose of this study is to compare the effect on 24-hour blood glucose patterns, HbA1c, and weight management when adding insulin glargine, or exenatide, or a combination of insulin glargine and exenatide to metformin.

Detailed Description: The primary objective of this study was to characterize the diurnal glucose patterns produced by insulin glargine alone, exenatide (GLP-1 agonist) alone and the combination of insulin glargine and exenatide in subjects taking stable dose of metformin and to evaluate their efficacy in terms of improvement in glucose exposure, variability, stability, incidence of hypoglycemia and weight management.

An ancillary study was approved as part of this study. The purpose of the ancillary study was to use CGM to characterize the glycemic response to a fixed breakfast meal consumed by study participants receiving different medications.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

Inclusion Criteria

Male or female subjects ≥18 and ≤75 years of age
Clinical diagnosis of type 2 diabetes
Diabetes duration ≥ 1 year
HbA1c ≥7.0%
Currently treated with metformin (HbA1c ≤9%) or metformin/sulfonylurea (SU) (HbA1c ≤8%)or SU alone (HbA1c ≤8%)

Exclusion Criteria

Previously treated with insulin or incretin-based therapy
Treated with a thiazolidinedione within past 6 weeks
Taken oral or injected prednisone or cortisone medications in the previous 30 days
Any pancreatic disease or at high risk of pancreatitis (history of alcohol abuse, active gallbladder disease)
Serum creatinine >1.4mg/dL (women) or >1.5 mg/dL (men)
eGFR (Estimated Glomerular Filtration Rate) <30 ml/min (using MDRD/ Modification of Diet in Renal Disease equation)
ALT(Alanine Transaminase) > 2x Upper Limit of Normal (ULN)
Presence of any severe medical or psychological condition or chronic conditions/infections that in the opinion of the Investigator would compromise he subject's safety or successful participation in the study
Currently pregnant or planning pregnancy during the study period
Unable to follow the study protocol
Unable to speak, read and write in English
Uncontrolled hyperglycemia with HbA1c > 9% on metformin or >8% on SU or metformin/SU combination or ketonuria requiring immediate insulin therapy
At the investigator's discretion for other medical or psychological reasons

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Exenatide	Exenatide	5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study
Insulin Glargine	Insulin Glargine	.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Exenatide + Insulin Glargine	Exenatide	Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study + Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Exenatide + Insulin Glargine	Insulin Glargine	Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study + Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results

Primary Outcome Measures

Name	Time	Method
HbA1c Change	baseline to final visit (32 weeks)	Measure the changes in HbA1C attributable to exenatide, insulin glargine and their combination. Employ CGM with AGP analysis to determine if there is an incremental benefit for subjects who do not reach target to add exenatide to insulin glargine or insulin glargine to exenatide in patients taking metformin.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Incidence of Hypoglycemia (Frequency)	baseline to final visit (32 weeks)	Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes. Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves- iv. Incidence of hypoglycemia (frequency) Change from baseline was calculated as mean incidence rate at baseline minus mean incidence rate at final visit (32 weeks)
Change From Baseline in Incidence of Hypoglycemia (Degree)	baseline to final visit (32 weeks)	Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes. Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves- iv. Incidence of hypoglycemia (degree) Change from baseline was calculated as mean incidence percentage at baseline minus mean incidence percentage at final visit (32 weeks)
Change From Baseline in Glucose Stability (Absolute Hourly Rate of Change in Median Curve)	baseline to final visit (32 weeks)	Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes. Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves iii. Glucose stability (absolute hourly rate of change in median curve) Change from baseline was calculated as mean absolute hourly rate of change in median curve at baseline minus rate at final visit (32 weeks). Mean absolute hourly rate of change in the smoothed median curve is calculated as delta subscript MC = (\\|p subscript 50 zero - p subscript 50 23\\|+Sum superscript 23 subscript i = 1\\| p subscript 50i - p subscript 50 i-1\\| over T. i = hour of day p subscript 50i = smoothed 50th percentile value for ith hour of day T = total # of non-missing hourly smoothed percentiles
Change From Baseline in CGM Glucose Variability	baseline to final visit (32 weeks)	Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes. Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves- ii. Glucose variability (inter-quartile range) IQR is the difference between the 75th and 25th percentiles. Change from baseline was calculated as IQR at baseline minus IQR value at final visit (32 weeks).
Change From Baseline in Glucose Exposure (Area Under the Diurnal Median Curve or AUC)	baseline - final visit (32 weeks)	Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes. Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves- i. Glucose exposure (area under the diurnal median curve) Change from baseline was calculated as area under the diurnal median curve at baseline minus AUC value at final visit (32 weeks). AUC is calculated using modified rectangle method AUC = sum of superscript 23, subscript i=0 P subscript 50i I = hour of day P subscript 50i = smoother 50th percentile value for ith hour of day
Change From Baseline in Weight Changes	baseline - final visit (32 weeks)	Measure the changes in weight attributable to exenatide, insulin glargine and their combinations. Employ CGM with AGP analysis to determine if there is an incremental benefit for subjects who do not reach target to add exenatide to insulin glargine or insulin glargine to exenatide in patients taking metformin. Change from baseline was calculated as weight in pounds at baseline minus weight in pounds at final visit (32 weeks).