Phase 3
Completed N=119
EQW, DAPA, EQW/DAPA, DAPA/MET ER and PHEN/TPM ER in Obese Women With PolycysticOvary Syndrome (PCOS)
Source: ClinicalTrials.gov NCT02635386 ↗Enrolled (actual)
119
Serious AEs
3.4%
Results posted
Jan 2021
Primary outcomePrimary: Oral Disposition (Insulin Sensitivity-insulin Secretion) Index — 471; 311; 503; 395 index score — p=<0.02
◆ Published Evidence
Established
91citations · ~18 / year
Exenatide, Dapagliflozin, or Phentermine/Topiramate Differentially Affect Metabolic Profiles in Polycystic Ovary Syndrome.
Summary
This is a randomized, single-blind, parallel 5 treatment group 24-week trial designed to directly compare the therapeutic effects of exenatide once weekly (EQW), dapagliflozin (DAPA), EQW plus DAPA, combined DAPA/metformin extended release (XR) and the weight loss medication, phentermine/topiramate extended release (PHEN/TPM ER) on metabolic and endocrinological parameters in overweight/obese non-diabetic women with PCOS. In this study, we will examine the efficacy of these therapies on metabolic parameters, body weight and body composition, anthropometric measurements, and reproductive function in a well-defined group of pre-menopausal overweight/obese, non-diabetic women with PCOS, focusing on their relationship to insulin resistance and obesity. We hope to determine which treatment(s) addressing the multifaceted disturbances of individual subgroups emerge as the preferable therapy.
Linked Publications
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Exenatide, Dapagliflozin, or Phentermine/Topiramate Differentially Affect Metabolic Profiles in Polycystic Ovary Syndrome.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Oral Disposition (Insulin Sensitivity-insulin Secretion) Index |
471; 311; 503; 395; 545 | <0.02 sig |
| SECONDARY Absolute Body Weight |
100.4; 102.6; 99; 101.2; 97 | <0.0001 sig |
| SECONDARY Body Mass Index (BMI) |
37.3; 37.4; 36.7; 37; 35.3 | <0.0001 sig |
| SECONDARY Change in Percent Body Weight |
3.8; 1.5; 6.9; 1.7; 8.1 | <0.0001 sig |
| SECONDARY Central Adiposity (Waist Circumference) |
104; 101; 106; 101.3; 97 | <0.0001 sig |
| SECONDARY Waist-to-Hip Ratio (WHR) |
.83; .79; .86; .83; .81 | <0.05 sig |
| SECONDARY Waist-to-Height Ratio (WHtR) |
.64; .61; .65; .61; .59 | <0.0001 sig |
| SECONDARY Total Fat Mass (kg) Evaluated by DEXA |
47.6; 47.8; 45.9; 48; 44.5 | <0.0001 sig |
| SECONDARY Total Body Fat (%) by DEXA |
46.1; 46.4; 45.8; 46.1; 45.2 | <0.0001 sig |
| SECONDARY Android-Gynoid Ratio (AGR) as Determined by DEXA |
1.07; 1.02; 1.04; 1.04; 1.03 | <0.01 sig |
| SECONDARY Trunk/Leg Fat Ratio by DEXA |
1.03; .95; .93; .98; .99 | <0.035 sig |
| SECONDARY Fasting Blood Glucose |
91; 93; 86.5; 89; 91.4 | <0.0001 sig |
| SECONDARY OGTT Mean Blood Glucose (MBG) |
118; 126.4; 112; 119; 113 | <0.02 sig |
| SECONDARY Fasting Insulin Sensitivity (HOMA-IR) |
3.7; 3.6; 2.6; 3.3; 3.4 | <0.035 sig |
| SECONDARY Matsuda Sensitivity Index Derived From the OGTT(SI OGTT) |
3.1; 3.6; 3.9; 4.8; 4.7 | <0.0001 sig |
| SECONDARY Corrected First Phase Insulin Secretion (IGI/HOMA-IR) |
1.03; 0.6; 0.91; 0.7; 1.1 | <0.04 sig |
| SECONDARY Total Cholesterol Levels |
189; 186; 185; 192; 178 | >0.05 |
| SECONDARY Triglyceride (TRG) Levels |
130; 132; 112; 105; 110 | <0.04 sig |
| SECONDARY Total Testosterone Concentrations |
38.8; 35; 42.6; 39.5; 45.5 | <0.0001 sig |
| SECONDARY Dehydroepiandrosterone Sulfate (DHEA-S) Levels |
165; 187; 169; 189; 201 | <0.05 sig |
| SECONDARY Free Androgen Index (FAI) |
5.3; 4.7; 5.2; 5.7; 5 | <0.001 sig |
| SECONDARY Systolic Blood Pressure (SBP) |
123.6; 123; 122; 128; 124 | <0.035 sig |
| SECONDARY Diastolic Blood Pressure (DBP) |
81; 79.8; 76; 82; 83.6 | <0.035 sig |
Eligibility Criteria
Inclusion Criteria
- Non-diabetic women (18-45 years)
- PCOS- NIH criteria hyperandrogenism and irregular menses
- Obese class I, II, and III (BMI >30 3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
- Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women, or estimated glomerular filtration rate (eGFR) 400 mg/dL)
- Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg)
- Use of hormonal medications, lipid-lowering (statins, etc.), anti-obesity drugs or weight loss medications (prescription or OTC) and medications known to exacerbate glucose tolerance (such as isotretinoin, hormonal contraceptives, gonadotropin-releasing hormone agonists, glucocorticoids, anabolic steroids, C-19 progestins) stopped for at least 8 weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha reductase inhibitors (finasteride, spironolactone, flutamide) stopped for at least 4 weeks
- Prior history of a malignant disease requiring chemotherapy
- Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status
- History of unexplained microscopic or gross hematuria, or microscopic hematuria at visit 1, confirmed by a follow-up sample at next scheduled visit.
- Presence of hypersensitivity to dapagliflozin or other SGLT2 inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions
- Known hypersensitivity or contraindications to use GLP1 receptor agonists (exenatide, liraglutide)
- Use of metformin, thiazolidinediones, GLP-1 receptor agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, SGLT2 inhibitors stopped for at least 4 weeks.
- Prior use of medication to treat diabetes except gestational diabetes
- Eating disorders (anorexia, bulimia) or gastrointestinal disorders
- Suspected pregnancy (documented negative serum pregnancy test), desiring pregnancy in next 6 months, 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
- Having a history of bariatric surgery
- Patient not willing to use two barrier method contraception during study period (unless sterilized or have an IUD)
- Patients with glaucoma or history of increased intraocular pressure, or use of any medications to treat increased intraocular pressure
- Debilitating psychiatric disorder such as psychosis or neurological condition that might confound outcome variables. Patients with a history of bipolar disorder or psychosis, greater than one lifetime, episode of major depression, current depression of moderate or greater severity (PHQ-9score of 10 or more), presence or history of suicidal behavior or ideation with some intent to act on it, or antidepressant use that has not been stable for at least 3 months will also be excluded.
- Inability or refusal to comply with protocol
- Current participation or participation in an experimental drug study in previous three months
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Data sourced from ClinicalTrials.gov (NCT02635386) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.