Metformin 2000 mg daily (QD) for 16 weeks

Saxagliptin-Metformin XR (combination pill)
5mg Saxagliptin/2000 mg Metformin XR QD for 16 weeks

Metformin 2000 mg QD for 16 weeks
Metformin XR: Start 2 pills (2 pills of 500 mg =1000mg XR) for 3 weeks
Increase to 4 pills as tolerated (4 pills of 500 mg XR =2000 mg XR) for remainder of study

Metformin XR

Saxagliptin 5 mg QD for 16 weeks
Saxagliptin: Start 1 pill (5 mg)) for 3 weeks
Remain at 1 pill (5mg dose) for remainder of study

Saxagliptin

Saxagliptin-Metformin XR (combination pill)
5mg Saxagliptin/2000 mg Metformin XR QD for 16 weeks
Saxagliptin-Metformin XR: Start 1 pill (2.5 mg/ 1000mg XR) for 3 weeks
Increase to 2 pills as tolerated (5mg/2000 mg XR) for remainder of study

Saxagliptin-Metformin XR

Total

All participants had to be 18 to 42 years to participate

All participants had to be female to qualify

Sex: Female, Male

Our patient population is approximately 64% Caucasian and 35% African -American. The remaining ethnicities comprise about 1%.

Race (NIH/OMB)

All participants were from Baton Rouge and surrounding parishes

Region of Enrollment

Glucose metabolic secretory status after drug treatment (normal, impaired or diabetic). We used the American Diabetes Association (ADA) definition of impairment which is fasting glucose greater than 100 mg/dL and/or 2 hour glucose greater than 140 mg/dL.

Glucose Metabolism

Post-treatment in insulin-sensitivity-secretion index . The insulin secretion-sensitivity index (IS-SI) provides an estimate of β-cell compensation relative to the prevailing insulin resistance, not absolute insulin secretion. It is derived by applying the concept of the disposition index (DI) to measurements obtained during the 2-h OGTT. The IS-SI, a surrogate measure of the DI derived from the OGTT (IGI multiplied by the SIOGTT], was calculated as the product of acute β-cell response [IGI] and Matsuda index (SIOGTT) based on the existence of the predicted hyperbolic relationship between these two measures

Oral Disposition Index

Fasting Glucose

Post-treatment mean blood glucose levels. Mean blood glucose (MBG) concentrations were calculated by summing glucose values obtained at 0,30,60 and 120 minutes during the OGTT and dividing by 4.

Mean Blood Glucose During the OGTT

Post-treatment insulin sensitivity index. The Matsuda index of whole-body insulin sensitivity is calculated from an oral glucose tolerance test (10,000/square root of [fasting glucose x fasting insulin] x [mean glucose x mean insulin during OGTT]), and is highly correlated with the rate of whole-body glucose disposal during the euglycemic insulin clamp

Matsuda Index of Insulin-Sensitivity (SI OGTT)

Post-treatment corrected early phase insulin secretion index (IGI/HOMA-IR). . Early pancreatic β-cell response is estimated as the insulinogenic index (IGI) derived from the ratio of the increment of insulin to that of glucose 30 minutes after a glucose load (insulin 30 min - insulin 0 min/glucose 30 min - glucose 0 min) corrected for by the relative level of insulin resistance (IGI/HOMA-IR which is estimated by homeostasis model assessment of insulin resistance using fasting insulin and glucose levels).

Pancreatic ß-cell Compensatory Function

Height and weight measurements were used to calculate body mass index (BMI), defined as kg/m2.

Body Mass Index at 16 Weeks

The circumference measurement was taken in the upright position using a 15-mm width flexible metric tape held close to the body but not tight enough to indent the skin. Waist circumference (WC) was measured in centimeters at the narrowest level midway between the lowest ribs and the iliac crest.

Waist Circumference at 16 Weeks

The number of menstrual cycles during the previous year was recorded and the average menstrual interval calculated by dividing 365 by the number of menstrual cycles in the previous year . During the study period, the patients in a menstrual diary recorded vaginal bleeding over 16 weeks. The effects of treatment intervention on menstrual cycle interval was calculated evaluated by dividing 112 days by the number of menstrual cycles recorded in each patient's menstrual cycle diary.

Menstrual Cycle Interval at 16 Weeks

The measure of TRG levels and HDL- cholesterol levels are used as an estimate of insulin sensitivity. A TRG/HDL-C ratio of greater than 3.0 is used as an indirect measure of insulin resistance

Triglyceride (TRG) /HDL-cholesterol Ratio

Hyperandrogenism is measured by a combination of total testosterone (T) and sex hormone binding globulin (SHBG). The FAI was calculated as the quotient 100 x T/SHBG; hyperandrogenism was defined by a FAI value >3.85.

Free Androgen Index (FAI)

The safety criteria will include laboratory values for liver enzymes and document the absence of pregnancy in all participants during the trial

Number of Participants With No Clinically Significant Changes in Liver Enzyme Levels or Positive Pregnancy Tests

Overall Study

Dr Karen Elkind-Hirsch

Polycystic Ovary Syndrome

Disorder of Glucose Regulation

Start 2 pills (2 pills of 500 mg =1000mg XR) for 3 weeks
Increase to 4 pills as tolerated (4 pills of 500 mg XR =2000 mg XR) for remainder of study

Start 1 pill (5 mg)) for 3 weeks
Remain at 1 pill (5mg dose) for remainder of study

Start 1 pill (2.5 mg/ 1000mg XR) for 3 weeks
Increase to 2 pills as tolerated (5mg/2000 mg XR) for remainder of study

Woman's Hospital

Saxagliptin + Metformin Compared to Saxagliptin or Metformin Monotherapy in PCOS Women With Impaired Glucose Homeostasis

Metabolic and Endocrine Effects of Combination of Metformin and DPP-4 Inhibitor Saxagliptin Compared to Saxagliptin or Metformin XR Monotherapy in Patients With PCOS and Impaired Glucose Regulation: A Single-blinded Randomized Pilot Study

Karen Elkind-Hirsch

Director of Research

Woman's

AstraZeneca

Twenty adult patients with type 1 diabetes, regularly attending the Division of Endocrinology and Metabolic Diseases of University of Verona School of Medicine, using continuous subcutaneous fast insulin analogue infusion (CSII) through a permanent pump and on subcutaneous glucose sensing will be enrolled.

Twenty healthy adult volunteers will be recruited.

Type 1 Diabetes Mellitus

Standard clinical parameters will be assessed in all patients.
Metabolic tests:
A. Euglycemic insulin clamp. A standard euglycemic insulin clamp will be carried out in type 1 diabetic patients to assess insulin sensitivity, as previously described (1).
B. Mixed meal test. All participants will ingest a standardized mixed meal and will be monitored for 300 minutes thereafter. Right before meal ingestion, a s.c. fast insulin analogue bolus will be administered by the pump
This test will determine the time courses of:
1. plasma glucose, 2. 13C/12C glucose ratio (hence, meal-derived and endogenous glucose), 3. insulin, 4. free fatty acids, 5. aminoacids, 6. glucagon, 7. incretin hormones 8. glucose control coefficients (CCs) during a mixed meal.

Clamp-Mixed Meal

Standard clinical parameters will be assessed in all subjects.
Metabolic tests:
A. IVGTT. A frequently sampled intravenous glucose tolerance test (IVGTT) in healthy controls will be carried out in study 1 and study 3 to assess insulin sensitivity.
B. Mixed meal test. All participants will ingest a standardized mixed meal and will be monitored for 300 minutes thereafter.
This test will determine the time courses of:
1. plasma glucose, 2.13C/12C glucose ratio (hence, meal-derived and endogenous glucose), 3. insulin, 4. free fatty acids, 5. aminoacids, 6. glucagon, 7. incretin hormones 8. glucose control coefficients (CCs) during a mixed meal.

IVGTT-Mixed Meal Arm

Clinical Research Center-University Hospital of Verona

Division of Endocrinology and Metabolic Diseases - University Hospital of Verona

Mixed Meal Test in Type 1 Diabetes on Insulin Pump Therapy: Optimization of Artificial Pancreas

Meal Glucose Regulation in Type 1 Diabetes on Insulin Pump Therapy: Towards a Better Understanding of the Glucose-Insulin System.

Timed curves of composite plasma glucose, meal-derived glucose, endogenous glucose, insulin, glucagon and incretin hormone concentrations in response to a mixed meal.
Composite glucose control coefficients (CCs) of each component of the glucose-insulin system at each time point of the mixed meal.

Composite timed curves of plasma free fatty and amino acid concentrations to a mixed meal.

hypoglycemia/protease

Saxagliptin + Metformin Compared to Saxagliptin or Metformin Monotherapy in PCOS Women With Impaired Glucose Homeostasis

Mixed Meal Test in Type 1 Diabetes on Insulin Pump Therapy: Optimization of Artificial Pancreas

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