EQW, DAPA, EQW/DAPA, DAPA/MET ER and PHEN/TPM ER in Obese... | NCT02635386

ID	Type	Description	Link
AZ ESR-14-10725	Other Grant/Funding Number	Astra Zeneca,L.P

Name	Class
AstraZeneca	INDUSTRY

Description Module

Detailed Description

Polycystic ovary syndrome is a heterogeneous condition characterized by disordered reproductive and metabolic function which accounts for the myriad of clinical features including androgen excess, chronic anovulation, insulin resistance adiposity, and dyslipidemia. This syndrome is highly prevalent, affecting between 8 and 18% of the female population, depending on the diagnostic criteria used. Hyperandrogenism, ovarian dysfunction and metabolic abnormalities - the main determinants of PCOS - all appear to be involved in a synergistic way in the pathophysiology of PCOS. Women with PCOS are more likely to be obese: between 38 and 88% of women with PCOS are overweight or obese, although PCOS can also manifest in lean women. Obesity, particularly abdominal obesity, plays a central role in the development of PCOS, and exacerbates the reproductive and metabolic dysfunction. Rather than absolute body weight, it is the distribution of fat that is important with central (visceral) adiposity being a risk factor. Visceral adipose tissue is more metabolically active than subcutaneous fat and the amount of visceral fat correlates with insulin resistance and hyperinsulinemia. Weight gain is also often an important pathogenic factor, with PCOS usually becoming clinically manifest in women with a presumable genetic predisposition for PCOS who subsequently gain weight. Therefore, environmental (particularly dietary) factors are important. However, BMI is also influenced by genetic factors such as the fat mass and obesity-associated protein, and obesity is a highly heritable condition. Therefore, the weight gain responsible for the manifestation of PCOS in many women with this condition is itself influenced by genetic factors. Ethnicity, genetic background, personal and family history, degree of obesity must all be taken into account because they might aggravate or even trigger metabolic disturbances women with PCOS. Moreover, the incidence of glucose intolerance, dyslipidemia, gestational diabetes, and type 2 diabetes (DM2) is increased in women with PCOS at all weight levels and at a young age. PCOS may be a more important risk factor than ethnicity or race for glucose intolerance in young women. The exact factors responsible for this excess risk in women with PCOS have not been identified; family history of DM 2, obesity, insulin resistance, beta cell (ß-cell) secretory dysfunction, and hyperandrogenism are possible candidates. With better understanding of its pathophysiology, the metabolic consequences of the syndrome are now evident. Therefore, these patients need to be followed up even after their presenting complaint has been adequately resolved.

Lifestyle modification is a key component for the improvement of reproductive function for overweight, anovulatory women with PCOS. Even a modest weight loss 5% of total body weight can restore ovulation in overweight women with PCOS. Features of PCOS (e.g., hirsutism, testosterone levels, insulin resistance, menstrual cyclicity and ovulation) showed marked improvements, and PCOS frequently resolved after substantial weight loss induced by bariatric surgery. Recently a number of anti-diabetes medications have been approved which facilitate weight loss and improve the underlying insulin resistance. We reported that treatment with the glucagon like peptide -1 (GLP-1) agonist, exenatide for 24 weeks was superior to single agent metformin treatment in improving insulin action and reducing body weight and hyperandrogenism in obese women with PCOS. We further observed exenatide treatment significantly improved first-phase insulin responses to oral glucose administration. Since aberrant first-phase insulin secretion and impaired suppression of endogenous glucose production are major contributors to postprandial hyperglycemia and development of type 2 diabetes, the effects of exenatide once weekly [EQW (2 mg)] to target these defects, and normalize glucose excursions are likely to be clinically significant in obese patients with PCOS. Sodium/glucose cotransporter 2 (SGLT-2) inhibitors are the newest class of medications for diabetes management that have not been investigated for use in the women with PCOS. The SGLT2 inhibitor, dapagliflozin [DAPA (10 mg/day)] has an insulin-independent action, promotes weight loss, has a low incidence of hypoglycemia, and complements the action of other antidiabetic agents. The loss of glucose with attendant caloric loss contributes to weight loss; in addition, improvements in β cell function have been seen. Because the SGLT2 inhibitors have a distinct mechanism of action that is independent of insulin secretion, the efficacy of this class of drugs is not anticipated to decline in the presence of severe insulin resistance. The weight loss seen with SGLT2 inhibitors is similar to that seen with glucagon-like peptide 1 agonists, and may be more acceptable because they are oral agents. The resulting weight loss will further assist in decreasing insulin resistance, leading to increased glucose disposal thus contributing to an increased insulin secretion-insulin sensitivity (ISSI) index, the primary outcomes measure.

The non-diabetic female with PCOS offers a unique model to study the relationship between insulin resistance and adiposity. Women with PCOS demonstrate abnormal body composition characterized by a greater percent body fat, body fat mass, and increased ratio of fat to lean mass (F/L ratio). Studies using dual-energy X-ray absorptiometry (DEXA) methodology report a higher degree of metabolic dysfunction in patients with PCOS which appears be directly associated with their higher F/L ratio. Given that monotherapy and combined therapy with exenatide once weekly (EQW),and dapagliflozin (DAPA) along with DAPA/ metformin XR therapy are associated with weight loss introduces a confounder to the current study since it prevents distinguishing direct effects of the compounds on β-cell function vs. effects due to reduced adiposity. To control for loss of body mass and provide appropriate intervention in the remaining study arm we propose the use of a comparator weight loss drug alone, combination phentermine (PHEN)/topiramate (TPM) extended release (ER). To avoid the confounding relationship of body fat and insulin resistance, we will enroll only obese non-diabetic women with PCOS. All patients will receive diet and lifestyle counselling, including advice on exercise, according to usual clinical routine commencing during the lead-in period and continuing throughout the study We propose 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 ER and the weight loss medication, phentermine/topiramate extended release (PHEN/TPM ER) on metabolic and endocrinological parameters in obese non-diabetic women with PCOS.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Exenatide once weekly (EQW )	Experimental	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks	Drug: Exenatide once weekly (EQW )
Dapagliflozin (DAPA)	Experimental	DAPA-10 mg oral pill once daily in am for 24 weeks	Drug: Dapagliflozin (DAPA)
EQW plus DAPA	Experimental	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks	Drug: EQW plus DAPA
Dapagliflozin plus Glucophage (MET ER)	Experimental	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks	Drug: Dapagliflozin plus Glucophage (MET ER)
Phentermine /Topiramate (PHEN/ TPM) ER	Active Comparator	Combination Phentermine /Topiramate ER -7.5 mg/46mg pill once daily in am for 24 weeks	Drug: Phentermine /Topiramate (PHEN/ TPM) ER

Name	Type	Description	Arm Group Labels	Other Names
Exenatide once weekly (EQW )	Drug	2 mg SC injection every 7 days	Exenatide once weekly (EQW )

Measure	Description	Time Frame
Oral Disposition (Insulin Sensitivity-insulin Secretion) Index	An estimation of β-cell compensatory function, the insulin secretion-sensitivity index (IS-SI) will be derived by applying the concept of the oral disposition index to measurements obtained during the 2-h OGTT and calculated as the index of insulin secretion factored by insulin sensitivity (ΔINS/ΔPG 30 x Matsuda SIOGTT) from the OGTT. A higher score shows improved pancreatic insulin responsiveness relative to resistance.	24 weeks of treatment

Measure	Description	Time Frame
Absolute Body Weight	Treatment effect on body weight at 24 weeks of treatment	24 weeks of treatment
Body Mass Index (BMI)	Treatment efficacy in reducing body mass at 24 weeks of treatment

Eligibility Module

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<45)
Willing to use effective contraception consistently during therapy which is defined as:
1. an intrauterine device, tubal sterilization, or male partner vasectomy, or
2. combination of two barrier methods with one being male condom.
Written consent for participation in the study

Exclusion Criteria:

Presence of significant systemic disease, heart problems including congestive heart failure, unstable angina or acute myocardial infarction, current infectious liver disease, acute stroke or transient ischemic attacks, history of pancreatitis, or diabetes mellitus (Type 1 or 2)
Any hepatic diseases in the past (infectious liver disease, viral hepatitis, toxic hepatic damage, jaundice of unknown etiology) or severe hepatic insufficiency and/or significant abnormal liver function tests defined as aspartate aminotransferase (AST) >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) <60 mL/min/1.73 m2) or history of unstable or rapidly progressing renal disease or end stage renal disease. Patients with a history of nephrolithiasis are also excluded due to increased association with kidney stone formation.
Uncontrolled thyroid disease (documented normal TSH), Cushing's syndrome, congenital adrenal hyperplasia or hyperprolactinemia
Significantly elevated triglyceride levels (fasting triglyceride > 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

-

Name	Affiliation	Role
Karen Elkind-Hirsch, PhD	Woman's Hospital, Louisiana	Principal Investigator
Drake Bellanger, MD	Woman's Hospital, Louisiana	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Woman's Hospital		Baton Rouge	Louisiana	70817	United States

PubMed Identifier	Type	Citation	Retractions
34097062	Derived	Elkind-Hirsch KE, Chappell N, Seidemann E, Storment J, Bellanger D. Exenatide, Dapagliflozin, or Phentermine/Topiramate Differentially Affect Metabolic Profiles in Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2021 Sep 27;106(10):3019-3033. doi: 10.1210/clinem/dgab408.

ID	Title	Description
FG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
FG001	Dapagliflozin (DAPA)

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
ICF	No	No	Yes	Informed Consent Form	Aug 31, 2018	Mar 14, 2019

Arm/Group Information

ID	Title	Description
BG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
BG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
BG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
BG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose
BG004	Phentermine /Topiramate (PHEN/ TPM) ER	Combination Phentermine /Topiramate ER -7.5 mg/46mg pill once daily in am for 24 weeks Phentermine /Topiramate (PHEN/ TPM) ER: PHEN 3.75/TPM ER 23mg - 1 pill by mouth once daily in am for 2 weeks. After 2 weeks, PHEN 7.5mg/TPM ER 46mg- 1 pill by mouth once daily in am
BG005	Total	Total of all reporting groups

Units	Counts
Participants	BG00023 BG00123 BG00222 BG00326 BG00425 BG005119

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Oral Disposition (Insulin Sensitivity-insulin Secretion) Index

An estimation of β-cell compensatory function, the insulin secretion-sensitivity index (IS-SI) will be derived by applying the concept of the oral disposition index to measurements obtained during the 2-h OGTT and calculated as the index of insulin secretion factored by insulin sensitivity (ΔINS/ΔPG 30 x Matsuda SIOGTT) from the OGTT. A higher score shows improved pancreatic insulin responsiveness relative to resistance.

Posted

Mean

Standard Error

index score

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose
OG004	Phentermine /Topiramate (PHEN/ TPM) ER	Combination Phentermine /Topiramate ER -7.5 mg/46mg pill once daily in am for 24 weeks Phentermine /Topiramate (PHEN/ TPM) ER: PHEN 3.75/TPM ER 23mg - 1 pill by mouth once daily in am for 2 weeks. After 2 weeks, PHEN 7.5mg/TPM ER 46mg- 1 pill by mouth once daily in am

Units	Counts
Participants	OG00020 OG00117 OG00220 OG003

Title

Denominators

Categories

Title	Measurements
	OG000471± 83 OG001311± 90 OG002503± 80 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002 OG003 OG004	Repeated Measure general linear model (SS/Drug treatments by visits) including arm of drug treatment as between subjects effect and visit (baseline and post 22-24 weeks treatment) as within subject effect	ANOVA	nested repeated measure	<0.02														Superiority

Secondary

Absolute Body Weight

Treatment effect on body weight at 24 weeks of treatment

Posted

Mean

Standard Error

kilogram

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Body Mass Index (BMI)

Treatment efficacy in reducing body mass at 24 weeks of treatment

Posted

Mean

Standard Error

kilogram/meter squared

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Change in Percent Body Weight

Treatment effect on change in percent body weight from baseline

Posted

Mean

Standard Error

percentage change in body weight

Change from baseline (time 0) to study end (24 weeks)

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Central Adiposity (Waist Circumference)

Treatment effect on loss of central adiposity after 24 weeks

Posted

Mean

Standard Error

centimeters

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Waist-to-Hip Ratio (WHR)

Treatment impact on central adiposity after 24 weeks

Posted

Mean

Standard Error

ratio

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Waist-to-Height Ratio (WHtR)

Treatment impact on WHtR which is a measure of central adiposity

Posted

Mean

Standard Error

ratio

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Total Fat Mass (kg) Evaluated by DEXA

Treatment impact on total fat mass by DEXA

Posted

Mean

Standard Error

kilogram

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Total Body Fat (%) by DEXA

Treatment impact on percent total body fat by DEXA

Posted

Mean

Standard Error

percent fat mass

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Android-Gynoid Ratio (AGR) as Determined by DEXA

treatment impact on measure of central adiposity as determined by android/gynoid ratio

Posted

Mean

Standard Error

ratio

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Trunk/Leg Fat Ratio by DEXA

Treatment impact on trunk/limb ratio (measure of central adiposity) by DEXA

Posted

Mean

Standard Error

ratio

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Fasting Blood Glucose

Treatment impact on fasting concentration of glucose in the blood

Posted

Mean

Standard Error

mg/dL

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

OGTT Mean Blood Glucose (MBG)

Treatment effect on MBG measured during the oral glucose tolerance test

Posted

Mean

Standard Error

mg/dL

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Fasting Insulin Sensitivity (HOMA-IR)

Treatment effect on the ratio HOMA-IR which is insulin resistance measure derived from fasting blood glucose and insulin and is calculated by insulin (mU/ml)*glucose (mmol/L)/22,5. The higher thenumber the more insulin resistant.

Posted

Mean

Standard Error

index score

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Matsuda Sensitivity Index Derived From the OGTT(SI OGTT)

The SI IOGTT is a measure of peripheral insulin sensitivity derived from the values of Insulin (microunits per milliliter) and Glucose (milligrams per deciliter) obtained from the OGTT and the corresponding fasting values. SI (OGTT) = 10,000/ [(G fasting x I fasting) x (G OGTTmean x I OGTTmean)], where fasting glucose and insulin data are taken from time 0 of the OGTT and mean data represent the average glucose and insulin values obtained during the entire OGTT. The square root is used to correct for nonlinear distribution of insulin, and 10,000 is a scaling factor in the equation. The higher value, the more sensitive to insulin.

Posted

Mean

Standard Error

index score

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am

Secondary

Corrected First Phase Insulin Secretion (IGI/HOMA-IR)

Treatment effect on insulin secretion from 0 to 30 minutes after glucose load corrected for by fasting insulin sensitivity. A higher score shows improved first phase insulin secretion in response to glucose

Posted

Mean

Standard Error

index score

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Total Cholesterol Levels

Treatment effect on blood concentrations of total cholesterol

Posted

Mean

Standard Error

mg/dL

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Triglyceride (TRG) Levels

Treatment effect on blood concentrations of triglycerides

Posted

Mean

Standard Error

mg/dL

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Total Testosterone Concentrations

Treatment effect on blood concentrations of total testosterone

Posted

Mean

Standard Error

ng/dL

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Dehydroepiandrosterone Sulfate (DHEA-S) Levels

Treatment effect on blood concentrations of DHEA-S

Posted

Mean

Standard Error

mcg/dL

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Free Androgen Index (FAI)

Treatment effect on FAI calculated from total testosterone divided by sex hormone binding globulin (SHBG) levels. A higher score indicates a worse outcome.

Posted

Mean

Standard Error

index score

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Systolic Blood Pressure (SBP)

Treatment effect on SBP after 24 weeks of treatment

Posted

Mean

Standard Error

mmHg

24 weeks treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Secondary

Diastolic Blood Pressure (DBP)

Treatment effect on DBP after 24 weeks

Posted

Mean

Standard Error

mmHg

24 weeks of treatment

ID	Title	Description
OG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days
OG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am
OG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am
OG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Exenatide Once Weekly (EQW )	EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days	23	2	23	10	23
EG001	Dapagliflozin (DAPA)	DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am	23	0	23	10	23
EG002	EQW Plus DAPA	EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am	22	0	22	13	22
EG003	Dapagliflozin Plus Glucophage (MET ER)	Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose	26	0	26	14	26
EG004	Phentermine /Topiramate (PHEN/ TPM) ER	Combination Phentermine /Topiramate ER -7.5 mg/46mg pill once daily in am for 24 weeks Phentermine /Topiramate (PHEN/ TPM) ER: PHEN 3.75/TPM ER 23mg - 1 pill by mouth once daily in am for 2 weeks. After 2 weeks, PHEN 7.5mg/TPM ER 46mg- 1 pill by mouth once daily in am	25	2	25	13	25

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Yeast infection or urinary tract infection	Renal and urinary disorders	Systematic Assessment	EG0000 affected23 at risk EG0016 affected23 at risk EG0027 affected22 at risk EG0037 affected26 at risk EG0040 affected25 at risk
Nausea and upset stomach	Gastrointestinal disorders	Systematic Assessment	EG0005 affected23 at risk EG0010 affected23 at risk EG0020 affected22 at risk EG003
Injection site reaction	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0005 affected23 at risk EG0010 affected23 at risk EG0024 affected22 at risk EG003
Vaginal irritation	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected23 at risk EG0011 affected23 at risk EG0021 affected22 at risk EG003
Rapid heartbeat	Cardiac disorders	Systematic Assessment	EG0000 affected23 at risk EG0011 affected23 at risk EG0020 affected22 at risk EG003
Insomnia	General disorders	Systematic Assessment	EG0000 affected23 at risk EG0010 affected23 at risk EG0020 affected22 at risk EG003
Fatigue	General disorders	Systematic Assessment	EG0000 affected23 at risk EG0010 affected23 at risk EG0020 affected22 at risk EG003
Lightheaded	General disorders	Systematic Assessment	EG0000 affected23 at risk EG0011 affected23 at risk EG0020 affected22 at risk EG003
Headache	General disorders	Systematic Assessment	EG0000 affected23 at risk EG0010 affected23 at risk EG0020 affected22 at risk EG003
Stuffy Nose	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected23 at risk EG0010 affected23 at risk EG0020 affected22 at risk EG003
Prolonged menstrual cycle	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected23 at risk EG0011 affected23 at risk EG0021 affected22 at risk EG003
Kidney Stone	Renal and urinary disorders	Systematic Assessment	EG0000 affected23 at risk EG0010 affected23 at risk EG0020 affected22 at risk EG003

ID	Term
D010048	Ovarian Cysts
D003560	Cysts
D009369	Neoplasms
D010049	Ovarian Diseases
D000291	Adnexal Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D000091662	Genital Diseases
D006058	Gonadal Disorders
D004700	Endocrine System Diseases
D050177	Overweight
D044343	Overnutrition
D009748	Nutrition Disorders
D009750	Nutritional and Metabolic Diseases
D001835	Body Weight
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D000077270	Exenatide
D052216	Glucagon-Like Peptide 1
C529054	dapagliflozin
D000077203	Sodium-Glucose Transporter 2 Inhibitors
D008687	Metformin
C576188	Qsymia

ID	Term
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D014688	Venoms
D045424	Complex Mixtures
D014118	Toxins, Biological
D001685	Biological Factors
D004763	Glucagon-Like Peptides
D052336	Proglucagon
D005768	Gastrointestinal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D045504	Molecular Mechanisms of Pharmacological Action
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses
D007004	Hypoglycemic Agents
D045505	Physiological Effects of Drugs
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals