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

• Status: Completed
• Trial end date: 2016-10-01
• Target enrollment: 0
• Participant gender: Female

Summary

The objective of the present proposal is to compare the clinical, endocrine and metabolic effects of therapy with combination saxagliptin and metformin to saxagliptin and metformin monotherapy in women with PCOS and prediabetic hyperglycemia (IFG, IGT or IFG/IGT). Saxagliptin is an oral dipeptidyl peptidase IV (DPP-4) inhibitor whose mechanism of action is to prolong the duration of blood glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels by inhibiting their degradation and thereby augmenting insulin secretion. This study will serve as a pilot investigation to open perspectives for future studies to explore the potential of combining anti-diabetic drugs with different mechanisms of action in in patients with PCOS and impaired glucose regulation (IGR), especially ones for whom standard treatment with metformin is less effective.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Woman's
• Collaborator: AstraZeneca
• Treatments: Biguanides; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Saxagliptin

Criteria

Inclusion Criteria:

• Females 18 years to 42 years of age with polycystic ovary syndrome(NIH PCOS criteria) with prediabetic hyperglycemia determined by an 75 gram oral glucose tolerance test (OGTT). Study subjects will be inclusive of PCOS women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT).

• Written consent for participation in the study

Exclusion Criteria:

• Presence of significant systemic disease, heart problems including congestive heart failure, history of pancreatitis, or diabetes mellitus (Type 1 or 2)

• Any hepatic diseases in the past (viral hepatitis, toxic hepatic damage, jaundice of unknown etiology), gallstones, abnormal liver function tests or renal impairment (elevated serum creatinine levels or abnormal creatinine clearance)

• Uncontrolled thyroid disease (documented normal TSH), Cushing's syndrome, congenital adrenal hyperplasia or hyperprolactinemia

• Significantly elevated triglyceride levels (fasting triglyceride > 400 mg %)

• Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg)

• Use of hormonal medications, drugs known to affect gastrointestinal motility, lipid-lowering (statins, etc.) and/or anti-obesity drugs or medications that interfere with carbohydrate metabolism (such as isotretinoin, hormonal contraceptives, gonadotropin releasing hormone (GnRH) analogues, glucocorticoids, anabolic steroids, C-19 progestins) for at least 8 weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha reductase inhibitors (finasteride, spironolactone, flutamide) for at least 4 weeks

• Prior history of a malignant disease requiring chemotherapy

• Known hypersensitivity or contraindications to use of insulin sensitizers such as metformin or thiazolidinediones

• History of hypersensitivity reaction to saxagliptin or other DPP-4 inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions)

• Current use of metformin, thiazolidinediones, glucagon-like peptide -1 receptor agonists, DPP-4 inhibitors, or weight loss medications (prescription or OTC) Patients must stop use of insulin sensitizers or antidiabetic medicines such as metformin for at least 4 weeks or thiazolidinediones, GLP1 agonists or DPPIV inhibitors for 8 weeks.

• Prior use of medication to treat diabetes except gestational diabetes

• Use of drugs known to exacerbate glucose tolerance

• Eating disorders (anorexia, bulimia) or gastrointestinal disorders

• Suspected pregnancy (documented negative serum pregnancy test), desiring pregnancy during the study treatment interval, breastfeeding, or known pregnancy in last 2 months

• Active or prior history of substance abuse (smoke or tobacco use within past 3 years) or significant intake of alcohol or history of alcoholism

• Patient not willing to use adequate barrier contraception during study period (unless sterilized or have an IUD).

• Debilitating psychiatric disorder such as psychosis or neurological condition that might confound outcome variables

• Inability or refusal to comply with protocol

• Not currently participating or having participated in an experimental drug study in previous three months