Outpatient Discharge Therapy With Saxagliptin+MetforminXR vs GlipizideXL for Type 2 Diabetes With Severe Hyperglycemia

NCT ID: NCT01267448

Last Updated: 2023-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-09
• Study Completion Date: 2015-07-25

Brief Summary

Saxagliptin + Metformin XR (S+M) will be effective in stabilizing blood glucose (BG) levels in patients with newly diagnosed type 2 diabetes (T2DM) with severe hyperglycemia (BG levels 300 to 450 mg/dl) and glucose toxicity and with no criteria for inpatient admission or occurrence of severe hypoglycemia compared to glipizide XL.

The study may provide preliminary evidence to support the role of S+M as a bridging, stabilizing and safe therapy in patients with severe hyperglycemia

Detailed Description

There is very little information regarding diabetes discharge regimens for patients with recently diagnosed diabetes (<1 year duration) who present with severe hyperglycemia (blood glucose 300-450 mg/dl) to the ED or other clinical settings and who do not need to be admitted.

A combination of Saxagliptin+Metformin XR, could be a potential drug combination to be tested as an initial treatment in these circumstances compared to Glipizide XL which was shown to be effective in our previous study. We expect Saxagliptin to improve beta cell function and decrease glucagon levels as was shown for the DPP-IV class medications and in turn improve blood glucose levels, while Metformin XR may reduce insulin resistance and hepatic glucose output. Such discharge therapy may help to prevent deterioration into acute metabolic complications (DKA or hyperosmolar states) and avoid hospitalization. A high proportion of patients may achieve glycemic targets without significant hypoglycemia as measured by self glucose monitoring and objectively by continuous glucose monitoring system (CGMS). Such an easy regimen may safely bridge the time gap until patients will be seen by their providers.

Conditions

Diabetes Mellitus Type 2; Hyperglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Saxagliptin + Metformin XR

Saxagliptin 5 mg + Metformin XR 1000 mg will be automatically titrated weekly in 2 weeks to Saxagliptin 5 mg + Metformin XR 2000 daily for a total duration of 12 weeks.

Group Type: ACTIVE_COMPARATOR

Saxagliptin + Metformin XR

Intervention Type: DRUG

The intervention group will receive Saxagliptin 5 mg daily for a total duration of 12 weeks.

Metformin XR

Intervention Type: DRUG

The intervention group will receive Metformin XR 1000 mg daily and will be automatically titrated weekly in 2 weeks to Metformin XR 2000 daily for a total duration of 12 weeks.

the Control goup Glipizide XL

The control group will receive Sulphonylurea (Glipizide XL 10mg orally) for a total duration of 12 weeks.

Group Type: ACTIVE_COMPARATOR

Glipizide XL

Intervention Type: DRUG

The control group will receive Glipizide XL (10mg orally) for a total duration of 12 weeks.

Interventions

Glipizide XL

The control group will receive Glipizide XL (10mg orally) for a total duration of 12 weeks.

Intervention Type: DRUG

Saxagliptin + Metformin XR

The intervention group will receive Saxagliptin 5 mg daily for a total duration of 12 weeks.

Intervention Type: DRUG

Metformin XR

The intervention group will receive Metformin XR 1000 mg daily and will be automatically titrated weekly in 2 weeks to Metformin XR 2000 daily for a total duration of 12 weeks.

Intervention Type: DRUG

Other Intervention Names

Glucotrol XL; Onglyza; Glucophage XR

Eligibility Criteria

Inclusion Criteria

1. Target Population

1. Subjects recently diagnosed with T2DM (less than 1 year duration) who are either drug naïve or who had not taken oral anti-diabetic agents or insulin for more than 2 weeks.

2. FBG and or RBG > 300mg/dl and < 450mg/dl

2. Age and Sex

1. Men and women aged 18 to 75 years of age.

2. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug to minimize the risk of pregnancy.

WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of the investigational product.

Exclusion Criteria

1. Sex and Reproductive Status

1. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the last dose of study drug.

2. Women who are pregnant or breastfeeding.

3. Women with a positive pregnancy test.

4. Sexually active fertile men not using effective birth control if their partners are WOCBP.

2. Target Disease Exceptions

1. Type 2 diabetes with weight less than 120 pounds

2. Type 1 diabetes

3. History of diabetic ketoacidosis or hyperosmolar nonketotic coma

3. Medical History and Concurrent Diseases

1. Age >75 years

2. History of congestive heart failure

3. Evidence of an impaired sensorium and/or dementia

4. Current history of alcohol or substance abuse

5. Patients with any acute or active chronic medical illness

4. Physical and Laboratory Test Findings

1. FBG and /or RGB < 300 mg/dl or >450 mg/dl

2. Unstable vitals signs (temperature >101 degrees Fahrenheit, systolic blood pressure <90 or >180 mmhg, diastolic blood pressure <60 or >110 mmhg, heart rate <60 or >120 beats/minute)

3. Electrolyte imbalances (serum bicarbonate level <20 mEq/L, serum sodium <125 or >150 mEq/L, serum potassium <3.5 or >5.5 mEq/L), serum creatinine more than 1.5 in males and 1.4 in females, creatinine clearance less than 60ml/min, liver enzymes 3 times above upper limit of normal range.

4. HbA1c > 12% (based on our previous study (4) patients with HbA1c of >12 had a high rate of non-responders)

5. Liver enzymes 3 times above upper limit of normal range.

6. Allergies and Adverse Drug Reactions -Subjects with a history of any serious hypersensitivity reaction to saxagliptin, glipizide or metformin XR.

5. Prohibited Treatments and/or Therapies

a)Treatment with systemic cytochrome P450 3A4 (CYP 3A4) inhibitors.

1. Prisoners or subjects who are involuntarily incarcerated.

2. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Cook County Health

OTHER_GOV

Sponsor Role: lead

Responsible Party

Leon Fogelfeld MD

Co-Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ambika Babu, MD,MS

Role: PRINCIPAL_INVESTIGATOR

John H Stroger Hospital of Cook County

Locations

John Stroger Hospital of Cook County

Chicago, Illinois, United States

Countries

United States

Other Identifiers

IRB-10-182

Identifier Type: -

Identifier Source: org_study_id