Obesity Android, Polycystic Ovary Syndrome, Pre Diabetes
Conditions
Keywords
prediabetes, PCOS, GLP-1 agonist, weight loss
Brief summary
There is a growing need to develop pharmacologic interventions to improve metabolic function in women with polycystic ovary syndrome (PCOS). Given that PCOS is a frequent condition and weight loss is essential but difficult to achieve, it is important to study if the effect on body weight reported in other studies can be confirmed in a selected population of hyperandrogenic patients, especially with medications currently approved for weight reduction. High dose liraglutide alone results in significant weight reduction in obese women without PCOS. There is limited data on weight loss with high dose liraglutide in non-diabetic females with PCOS treated with this agent . Studies on the effect of anti-obesity medication combined with lifestyle changes on body weight and composition and androgen excess in obese women diagnosed with PCOS are lacking. The investigators aim to elucidate the most efficacious weight reduction regime in obese PCOS women. The investigators further hope to determine which treatment(s) addressing the multifaceted disturbances of this disorder in patients with PCOS and obesity emerges as the preferable therapy.
Detailed description
The drug, liraglutide 3.0 mg was approved for chronic weight management in management in obese adults with an initial BMI of 30 kg/m2 or greater or in overweight adults BMI of 27 kg/m2 or greater with at least one weight-related co-morbid condition as an adjunct to a reduced-calorie diet and increased physical activity. Liraglutide is an acylated human glucagon-like peptide -1 (GLP-1) analog that binds to and activates the GLP-1 receptor. It lowers body weight through decreased caloric intake while stimulating insulin secretion and reducing glucagon via a glucose-dependent mechanism. For obesity management, patients may lose weight with GLP-1 receptor agonists due to other unique actions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can slow gastric emptying and increase satiety. While predictors of weight loss success for the general population are available (protein intake, weight loss medications), predictors of weight loss success may differ between normal and hyperandrogenic women. Glucagon-like peptide 1 agonists are linked with dose dependent weight lowering potential in different obesity related populations. The weight loss effects of GLP-1RAs previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to patients with PCOS. Given this lack of information, the aim of the present study was to investigate the effects of liraglutide 3mg vs. placebo on body composition as well as hormonal and metabolic features in non-diabetic obese women with PCOS.The non-diabetic obese female with PCOS offers a unique model to study the relationship between insulin resistance and adiposity. The investigators propose a double-blind, placebo-controlled 30-week trial designed to directly examine the therapeutic effects of liraglutide 3 mg (LIRA 3 mg) compared to placebo on body weight, hormonal and cardiometabolic parameters in obese non-diabetic women with PCOS. All patients will receive diet and lifestyle counseling, including advice on exercise commencing during the lead-in period and continuing throughout the study. In this study, the investigators will examine the efficacy of LIRA 3mg on body weight and body composition, reproductive function metabolic parameters and cardiovascular risk factors in a well-defined group of pre-menopausal obese non-diabetic women with hyperandrogenism, focusing on the relationship to obesity and insulin resistance.
Interventions
daily sc injection of liraglutide with final dose of 3mg daily
DRUGPlacebo Liraglutide Pen Injector
daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo
Sponsors
Novo Nordisk A/S
Woman's
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double- Blind 2:1 Drug: Placebo
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Female gender * 18-45 years of age * BMI ≥30 kg/m2 or BMI ≥27 kg/m2 with one or more obesity-associated co-morbid conditions (e.g. hypertension, and dyslipidemia) * PCOS- NIH criteria hyperandrogenism and irregular menstrual cyclicity * Non-diabetic as determined by a 75 gram oral glucose tolerance test (OGTT) and hemoglobin A1C. Non-diabetic is inclusive of women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT). Participants with diabetes will be excluded * Willing to use effective contraception consistently during therapy which is defined as: * an intrauterine device, tubal sterilization, or male partner vasectomy, or * combination of two barrier methods with one being male condom. * Written consent for participation in the study
Exclusion criteria
* Presence of significant systemic disease, cerebrovascular disease, clinically significant cardiac abnormalities or 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 eGFR \<60 mL/min/1.73 m2) or history of unstable or rapidly progressing renal disease or end stage renal disease. * Uncontrolled thyroid disease (documented normal TSH), Cushing's syndrome, congenital adrenal hyperplasia or clinically significant elevations in prolactin levels. The clinical significance of prolactin levels will be determined by the treating physician * Significantly elevated triglyceride levels (fasting triglyceride \> 400 mg %) * Untreated or poorly controlled hypertension (sitting blood pressure \> 160/95 mm Hg) * Use of hormonal medications, the use of medications that cause clinically significant weight gain or loss (prescription or OTC) and medications known to exacerbate glucose tolerance (such as isotretinoin, hormonal contraceptives, GnRH analogues, glucocorticoids, anabolic steroids, C-19 progestins) including herbal medicines 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 * Family or personal history of familial medullary thyroid carcinoma or multiple endocrine neoplasia type 2 * Known hypersensitivity or contraindications to use GLP1 receptor agonists * Use of metformin, thiazolidinediones, GLP-1 receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium/glucose co-transporter 2 (SGLT2) inhibitors or weight loss medications (prescription or OTC) 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 15 months, breastfeeding, or known pregnancy in last three months * Active or prior history of substance abuse (smoke or tobacco use within past 6 months) or significant intake of alcohol * Previous bariatric surgery or device intervention for obesity * Patient not willing to use barrier contraception during study period (unless sterilized or have an IUD) * History of major depressive or other severe psychiatric disorders * Inability or refusal to comply with protocol * Currently participating or having participated in an experimental drug study in previous three months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Body Weight (BW) | 32 weeks of treatment | Treatment impact on change in body weight after 32 weeks of treatment. |
| Free Androgen Index (FAI) | 32 weeks of treatment | Drug treatment effect on free androgen levels as calculated as FAI= total testosterone (T) concentrations divided by sex hormone binding globulin (SHBG) levels. A higher score indicates a worse outcome (more androgenic). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 5% Weight Loss From Baseline | 32 weeks of treatment | Frequency of patients achieving 5% weight loss from baseline with treatment |
| 10% Body Weight Loss From Baseline | 32 weeks of treatment | Frequency of patients with at least 10% reduction in body weight from baseline |
| Abdominal Adiposity (Waist Circumference [WC] | 32 weeks of treatment | Treatment effect on loss of WC (abdominal adiposity) with drug treatment |
| Waist-to-Hip Ratio | 32 weeks of treatment | Change in central adiposity with treatment as measured by WHR. A reduction in ratio indicates a decrease in truncal fat. |
| Waist-to Height Ratio [WHtR]) | 32 weeks of treatment | Treatment effect on loss of central adiposity as determined by WHt ratio. The lower the ratio indicates less abdominal adiposity. |
| Total Fat Mass Evaluated by DEXA | 32 weeks of treatment | Treatment effect on reduction of fat mass (kg) |
| Total Body Fat (%) by DXA | 32 weeks of treatment | Treatment effect on reduction of percent body fat by DXA |
| Android-Gynoid Ratio (AGR) by DXA | 32 weeks of treatment | Treatment impact on AGR, measure of central adiposity, as determined by DXA. A lower AGR indicates a reduction in central adiposity. |
| Trunk/Leg Fat Ratio (TLR) by DXA | 32 weeks of treatment | Treatment impact on TLR after 32 weeks. A reduction in TLR indicates a loss of central fat. |
| Menstrual Cycle Frequency | 32 weeks of treatment | Drug treatment impact on normalization of cycle frequency (cycle every 28-30 days). All cycle data is expressed as number of menses annualized to one year. |
| Total Testosterone Concentrations (T) | 32 weeks of treatment | Drug treatment effect on total testosterone concentrations |
| Adrenal Dehydroepiandrosterone Sulfate (DHEAS) | 32 weeks of treatment | Treatment efficacy in reducing adrenal hyperandrogenism |
| Body Mass Index (BMI) | 32 weeks of treatment | Treatment effect in reducing body mass |
| OGTT Mean Blood Glucose (MBG) | 32 weeks of treatment | Treatment effect on MBG measured during the oral glucose tolerance test. A decrease in MBG shows improvement in glycemia. |
| Fasting Insulin Sensitivity (HOMA-IR) | 32 weeks of treatment | Treatment effect on the HOMA-IR which is an insulin resistance measured derived from fasting blood glucose and insulin . The higher the number the more insulin resistant. |
| Matsuda Insulin Sensitivity Index Derived From the OGTT (SI OGTT) | 32 weeks of treatment | The SI OGTT is a measure of peripheral insulin sensitivity derived from the insulin and glucoses measured during an OGTT. A increase in SI OGTTindicates greater insulin sensitivity |
| Corrected First Phase Insulin Secretion (IGI/HOMA-IR) | 32 weeks of treatment | 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. |
| Insulin Secretion- Insulin Sensitivity Index (Oral Disposition Index-IS-SI) | 32 weeks of treatment | Treatment effect on an estimation of Beta cell compensatory function, the IS-SI is derived by applying the concept of the disposition index to measurements obtained during the 2 hour OGTT and calculated as the index of insulin secretion factored by insulin sensitivity. A higher score shows improved pancreatic beta cell function relative to insulin sensitivity. |
| Total Cholesterol Levels | 32 weeks of treatment | Treatment impact on improving total cholesterol levels |
| High Density Lipoprotein Cholesterol (HDL-C) | 32 weeks of treatment | Impact of treatment on HDL levels after 32 weeks of treatment |
| Triglyceride Levels (TRG) | 32 weeks of treatment | Drug effect of TRG levels after treatment |
| Triglyceride to HDL-Cholesterol Ratio (TRG/HDL-C) | 32 weeks of treatment | Treatment impact on TRG/HDL-C ratio which is a simple measure to estimate insulin action. A decrease in ratio indicates improvement in insulin sensitivity. |
| Triglyceride and Glucose Index (TyG) | 32 weeks of treatment | Treatment impact on the TyG index which estimates insulin resistance. A reduction in TyG indicates an improvement in insulin action. |
| Systolic Blood Pressure | 32 weeks of treatment | Treatment impact on systolic blood pressure |
| Diastolic Blood Pressure (BP) | 32 weeks of treatment | Treatment impact on reducing diastolic blood pressure |
| Fasting Blood Glucose (FG) | 32 weeks of treatment | Treatment effect on fasting glucose prior to an oral glucose tolerance test (OGTT) |
| Change in Percent Body Weight | Change from baseline (time 0) to study end (32 weeks) | Treatment effect on reducing body weight expressed as percent body weight loss from baseline |
Countries
United States
Participant flow
Recruitment details
88 recruited, 82 met criteria and randomized Six excluded after consenting
Participants by arm
| Arm | Count |
|---|---|
| Liraglutide Pen Injector (Saxenda) Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily
Liraglutide Pen Injector \[Saxenda\]: daily sc injection of liraglutide with final dose of 3mg daily | 55 |
| Placebo Liraglutide Pen Injector Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily
Placebo Liraglutide Pen Injector: daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo | 27 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 0 |
| Overall Study | Family member COVID exposure | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Medication concerns | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Pregnancy | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Liraglutide Pen Injector (Saxenda) | Placebo Liraglutide Pen Injector | Total |
|---|---|---|---|
| Age, Continuous | 31.1 years STANDARD_DEVIATION 6 | 31.8 years STANDARD_DEVIATION 5.6 | 31.3 years STANDARD_DEVIATION 5.8 |
| Body mass Index | 42 kg/m^2 STANDARD_DEVIATION 6.7 | 43.9 kg/m^2 STANDARD_DEVIATION 7.5 | 42.4 kg/m^2 STANDARD_DEVIATION 7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 9 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 42 Participants | 18 Participants | 60 Participants |
| Region of Enrollment United States | 55 participants | 27 participants | 82 participants |
| Sex: Female, Male Female | 55 Participants | 27 Participants | 82 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 27 |
| other Total, other adverse events | 40 / 55 | 8 / 27 |
| serious Total, serious adverse events | 0 / 55 | 0 / 27 |
Outcome results
Primary
Absolute Body Weight (BW)
Treatment impact on change in body weight after 32 weeks of treatment.
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Absolute Body Weight (BW) | 104.7 kilogram | Standard Error 2.9 |
| Placebo Liraglutide Pen Injector | Absolute Body Weight (BW) | 117.9 kilogram | Standard Error 5 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.002ANOVA
Primary
Free Androgen Index (FAI)
Drug treatment effect on free androgen levels as calculated as FAI= total testosterone (T) concentrations divided by sex hormone binding globulin (SHBG) levels. A higher score indicates a worse outcome (more androgenic).
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Free Androgen Index (FAI) | 5.98 index score | Standard Error 0.6 |
| Placebo Liraglutide Pen Injector | Free Androgen Index (FAI) | 6.4 index score | Standard Error 0.75 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.006ANOVA
Secondary
10% Body Weight Loss From Baseline
Frequency of patients with at least 10% reduction in body weight from baseline
Time frame: 32 weeks of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Liraglutide Pen Injector (Saxenda) | 10% Body Weight Loss From Baseline | 13 Participants |
| Placebo Liraglutide Pen Injector | 10% Body Weight Loss From Baseline | 2 Participants |
p-value: <0.049Wilcoxon (Mann-Whitney)
Secondary
5% Weight Loss From Baseline
Frequency of patients achieving 5% weight loss from baseline with treatment
Time frame: 32 weeks of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Liraglutide Pen Injector (Saxenda) | 5% Weight Loss From Baseline | 25 Participants |
| Placebo Liraglutide Pen Injector | 5% Weight Loss From Baseline | 5 Participants |
p-value: <0.007Wilcoxon (Mann-Whitney)
Secondary
Abdominal Adiposity (Waist Circumference [WC]
Treatment effect on loss of WC (abdominal adiposity) with drug treatment
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Abdominal Adiposity (Waist Circumference [WC] | 100.9 centimeters | Standard Error 2 |
| Placebo Liraglutide Pen Injector | Abdominal Adiposity (Waist Circumference [WC] | 109.9 centimeters | Standard Error 3.3 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.011ANOVA
Secondary
Adrenal Dehydroepiandrosterone Sulfate (DHEAS)
Treatment efficacy in reducing adrenal hyperandrogenism
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Adrenal Dehydroepiandrosterone Sulfate (DHEAS) | 177.1 mcg/dL | Standard Error 14.2 |
| Placebo Liraglutide Pen Injector | Adrenal Dehydroepiandrosterone Sulfate (DHEAS) | 171.3 mcg/dL | Standard Error 16.8 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: >0.05ANOVA
Secondary
Android-Gynoid Ratio (AGR) by DXA
Treatment impact on AGR, measure of central adiposity, as determined by DXA. A lower AGR indicates a reduction in central adiposity.
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Android-Gynoid Ratio (AGR) by DXA | 1.05 ratio | Standard Error 0.01 |
| Placebo Liraglutide Pen Injector | Android-Gynoid Ratio (AGR) by DXA | 1.08 ratio | Standard Error 0.03 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.034ANOVA
Secondary
Body Mass Index (BMI)
Treatment effect in reducing body mass
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Body Mass Index (BMI) | 39.1 kilogram/meter squared | Standard Error 1.1 |
| Placebo Liraglutide Pen Injector | Body Mass Index (BMI) | 43.4 kilogram/meter squared | Standard Error 1.8 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.001ANOVA
Secondary
Change in Percent Body Weight
Treatment effect on reducing body weight expressed as percent body weight loss from baseline
Time frame: Change from baseline (time 0) to study end (32 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Change in Percent Body Weight | 5.7 percentage loss in body weight | Standard Error 0.75 |
| Placebo Liraglutide Pen Injector | Change in Percent Body Weight | 1.4 percentage loss in body weight | Standard Error 1.09 |
p-value: <0.002ANOVA
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.
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Corrected First Phase Insulin Secretion (IGI/HOMA-IR) | 1.01 index score | Standard Error 0.18 |
| Placebo Liraglutide Pen Injector | Corrected First Phase Insulin Secretion (IGI/HOMA-IR) | 0.8 index score | Standard Error 0.16 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.042ANOVA
Secondary
Diastolic Blood Pressure (BP)
Treatment impact on reducing diastolic blood pressure
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Diastolic Blood Pressure (BP) | 77.6 mmHg | Standard Error 1.6 |
| Placebo Liraglutide Pen Injector | Diastolic Blood Pressure (BP) | 78.1 mmHg | Standard Error 1.3 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: >0.05ANOVA
Secondary
Fasting Blood Glucose (FG)
Treatment effect on fasting glucose prior to an oral glucose tolerance test (OGTT)
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Fasting Blood Glucose (FG) | 90.2 mg/dL | Standard Error 1.3 |
| Placebo Liraglutide Pen Injector | Fasting Blood Glucose (FG) | 94.3 mg/dL | Standard Error 2.2 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.021ANOVA
Secondary
Fasting Insulin Sensitivity (HOMA-IR)
Treatment effect on the HOMA-IR which is an insulin resistance measured derived from fasting blood glucose and insulin . The higher the number the more insulin resistant.
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Fasting Insulin Sensitivity (HOMA-IR) | 4.1 index score | Standard Error 0.6 |
| Placebo Liraglutide Pen Injector | Fasting Insulin Sensitivity (HOMA-IR) | 5.2 index score | Standard Error 1.1 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.035ANOVA
Secondary
High Density Lipoprotein Cholesterol (HDL-C)
Impact of treatment on HDL levels after 32 weeks of treatment
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | High Density Lipoprotein Cholesterol (HDL-C) | 41 mg/dL | Standard Error 1.8 |
| Placebo Liraglutide Pen Injector | High Density Lipoprotein Cholesterol (HDL-C) | 42 mg/dL | Standard Error 2.3 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: >0.05ANOVA
Secondary
Insulin Secretion- Insulin Sensitivity Index (Oral Disposition Index-IS-SI)
Treatment effect on an estimation of Beta cell compensatory function, the IS-SI is derived by applying the concept of the disposition index to measurements obtained during the 2 hour OGTT and calculated as the index of insulin secretion factored by insulin sensitivity. A higher score shows improved pancreatic beta cell function relative to insulin sensitivity.
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Insulin Secretion- Insulin Sensitivity Index (Oral Disposition Index-IS-SI) | 532 index score | Standard Error 91 |
| Placebo Liraglutide Pen Injector | Insulin Secretion- Insulin Sensitivity Index (Oral Disposition Index-IS-SI) | 416 index score | Standard Error 69.7 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.033ANOVA
Secondary
Matsuda Insulin Sensitivity Index Derived From the OGTT (SI OGTT)
The SI OGTT is a measure of peripheral insulin sensitivity derived from the insulin and glucoses measured during an OGTT. A increase in SI OGTTindicates greater insulin sensitivity
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Matsuda Insulin Sensitivity Index Derived From the OGTT (SI OGTT) | 3.7 index score | Standard Error 0.43 |
| Placebo Liraglutide Pen Injector | Matsuda Insulin Sensitivity Index Derived From the OGTT (SI OGTT) | 3.0 index score | Standard Error 0.48 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.028ANOVA
Secondary
Menstrual Cycle Frequency
Drug treatment impact on normalization of cycle frequency (cycle every 28-30 days). All cycle data is expressed as number of menses annualized to one year.
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Menstrual Cycle Frequency | 8.65 menses per year | Standard Error 0.4 |
| Placebo Liraglutide Pen Injector | Menstrual Cycle Frequency | 4.8 menses per year | Standard Error 0.65 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.0001ANOVA
Secondary
OGTT Mean Blood Glucose (MBG)
Treatment effect on MBG measured during the oral glucose tolerance test. A decrease in MBG shows improvement in glycemia.
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | OGTT Mean Blood Glucose (MBG) | 109.4 mg/dL | Standard Error 2.9 |
| Placebo Liraglutide Pen Injector | OGTT Mean Blood Glucose (MBG) | 125.5 mg/dL | Standard Error 4.8 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.009ANOVA
Secondary
Systolic Blood Pressure
Treatment impact on systolic blood pressure
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Systolic Blood Pressure | 116.8 mmHg | Standard Error 2.7 |
| Placebo Liraglutide Pen Injector | Systolic Blood Pressure | 123.3 mmHg | Standard Error 2.4 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: >0.05ANOVA
Secondary
Total Body Fat (%) by DXA
Treatment effect on reduction of percent body fat by DXA
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Total Body Fat (%) by DXA | 46.0 percent fat mass | Standard Error 0.9 |
| Placebo Liraglutide Pen Injector | Total Body Fat (%) by DXA | 47.9 percent fat mass | Standard Error 0.96 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.028ANOVA
Secondary
Total Cholesterol Levels
Treatment impact on improving total cholesterol levels
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Total Cholesterol Levels | 176 mg/dL | Standard Error 5.3 |
| Placebo Liraglutide Pen Injector | Total Cholesterol Levels | 178 mg/dL | Standard Error 8.8 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: >0.05ANOVA
Secondary
Total Fat Mass Evaluated by DEXA
Treatment effect on reduction of fat mass (kg)
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Total Fat Mass Evaluated by DEXA | 49.3 kilogram | Standard Error 2.1 |
| Placebo Liraglutide Pen Injector | Total Fat Mass Evaluated by DEXA | 56.8 kilogram | Standard Error 3.3 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.018ANOVA
Secondary
Total Testosterone Concentrations (T)
Drug treatment effect on total testosterone concentrations
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Total Testosterone Concentrations (T) | 45.4 ng/dL | Standard Error 3 |
| Placebo Liraglutide Pen Injector | Total Testosterone Concentrations (T) | 46.8 ng/dL | Standard Error 4.1 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: >0.05ANOVA
Secondary
Triglyceride and Glucose Index (TyG)
Treatment impact on the TyG index which estimates insulin resistance. A reduction in TyG indicates an improvement in insulin action.
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Triglyceride and Glucose Index (TyG) | 8.39 index score | Standard Error 0.07 |
| Placebo Liraglutide Pen Injector | Triglyceride and Glucose Index (TyG) | 8.5 index score | Standard Error 0.09 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.01ANOVA
Secondary
Triglyceride Levels (TRG)
Drug effect of TRG levels after treatment
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Triglyceride Levels (TRG) | 109 mg/dL | Standard Error 7.7 |
| Placebo Liraglutide Pen Injector | Triglyceride Levels (TRG) | 114 mg/dL | Standard Error 11 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.016ANOVA
Secondary
Triglyceride to HDL-Cholesterol Ratio (TRG/HDL-C)
Treatment impact on TRG/HDL-C ratio which is a simple measure to estimate insulin action. A decrease in ratio indicates improvement in insulin sensitivity.
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Triglyceride to HDL-Cholesterol Ratio (TRG/HDL-C) | 2.9 ratio | Standard Error 0.26 |
| Placebo Liraglutide Pen Injector | Triglyceride to HDL-Cholesterol Ratio (TRG/HDL-C) | 3.0 ratio | Standard Error 0.45 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.028ANOVA
Secondary
Trunk/Leg Fat Ratio (TLR) by DXA
Treatment impact on TLR after 32 weeks. A reduction in TLR indicates a loss of central fat.
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Trunk/Leg Fat Ratio (TLR) by DXA | 1.02 ratio | Standard Error 0.03 |
| Placebo Liraglutide Pen Injector | Trunk/Leg Fat Ratio (TLR) by DXA | 1.07 ratio | Standard Error 0.04 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.035ANOVA
Secondary
Waist-to Height Ratio [WHtR])
Treatment effect on loss of central adiposity as determined by WHt ratio. The lower the ratio indicates less abdominal adiposity.
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Waist-to Height Ratio [WHtR]) | 0.62 ratio | Standard Error 0.014 |
| Placebo Liraglutide Pen Injector | Waist-to Height Ratio [WHtR]) | 0.67 ratio | Standard Error 0.02 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.048ANOVA
Secondary
Waist-to-Hip Ratio
Change in central adiposity with treatment as measured by WHR. A reduction in ratio indicates a decrease in truncal fat.
Time frame: 32 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide Pen Injector (Saxenda) | Waist-to-Hip Ratio | 0.81 ratio | Standard Error 0.009 |
| Placebo Liraglutide Pen Injector | Waist-to-Hip Ratio | 0.85 ratio | Standard Error 0.015 |
Comparison: Repeated measures general linear model (SS/drug treatments by visits) where arm of drug therapy as between subjects effect and visit (baseline and 32 weeks of treatment) as within subject effectp-value: <0.038ANOVA