Adverse reactions
6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: Risk of Thyroid C-Cell Tumors [see Warnings and Precautions ( 5.1 )] Acute Pancreatitis [see Warnings and Precautions ( 5.2 )] Severe Gastrointestinal Reactions [see Warnings and Precautions ( 5.3 )] Acute Kidney Injury Due to Volume Depletion [see Warnings and Precautions ( 5.4 )] Hypoglycemia [see Warnings and Precautions ( 5.5 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.6 )] Diabetic Retinopathy Complications in Patients with Type 2 Diabetes [see Warnings and Precautions ( 5.7 )] Acute Gallbladder Disease [see Warnings and Precautions ( 5.8 )] Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.9 )] Most common adverse reactions, reported in ≥5% of patients treated with FOUNDAYO, are nausea, constipation, diarrhea, vomiting, dyspepsia, abdominal pain, headache, abdominal distension, fatigue, eructation, gastroesophageal reflux disease, flatulence, and hair loss. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of FOUNDAYO has been established in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition based on adequate and well-controlled trials of an investigational orforglipron formulation (Trials 1 and 2), referred to in this section as FOUNDAYO [see Clinical Studies ( 14 )] . This section of labeling presents safety data from administration of the investigational orforglipron formulation shown as equivalent dosages of once daily FOUNDAYO [see Dosage and Administration ( 2.1 )] . Adverse Reactions in Patients in Weight Management Clinical Trials Pool of Two Placebo-Controlled Clinical Trials: FOUNDAYO was evaluated for safety in a pool of two randomized, double-blind, placebo-controlled trials that included 3155 adult patients with obesity or overweight treated with FOUNDAYO once daily for up to 72 weeks and a 2-week off-drug follow-up period (Trial 1 and Trial 2) [see Clinical Studies ( 14 )] . The mean age of patients was 49 years and 41% were male. The population was 60% White, 25% Asian, 8% Black or African American, and 0.3% American Indian or Alaska Native; 35% identified as Hispanic or Latino ethnicity. At baseline, patients had an average BMI of 36.5 kg/m 2 , 51% with a BMI ≥35 kg/m 2 , 50% with hypertension, 49% with dyslipidemia, 31% with type 2 diabetes, 11% with obstructive sleep apnea, 3% with coronary artery disease, and 3% with cerebrovascular disease. Across both trials, 8% of patients treated with FOUNDAYO (5.5 mg, 6%; 9 mg, 9%; and 17.2 mg, 10%) once daily permanently discontinued treatment as a result of adverse reactions compared to 3% of patients receiving placebo. The majority of patients (5%) who discontinued FOUNDAYO due to adverse reactions did so due to gastrointestinal adverse reactions. Common Adverse Reactions Table 1 shows common adverse reactions associated with the use of once daily FOUNDAYO in the pool of two placebo-controlled trials for weight management (Trials 1 and 2). These adverse reactions occurred more commonly with once daily FOUNDAYO than with placebo and occurred in at least 5% of patients treated with FOUNDAYO. Table 1: Adverse Reactions Reported in ≥5% of FOUNDAYO-treated Adult Patients with Obesity or Overweight (With or Without Type 2 Diabetes) in Pool of Placebo-Controlled Trials (Trials 1 and 2) a Includes other related terms. Adverse Reaction Placebo (N=1,576) % FOUNDAYO 5.5 mg once daily (N=1,051) % FOUNDAYO 9 mg once daily (N=1,055) % FOUNDAYO 17.2 mg once daily (N=1,049) % Nausea 10 26 34 35 Constipation 9 20 27 24 Diarrhea 11 21 23 25 Vomiting 4 13 21 24 Dyspepsia 4 12 16 13 Abdominal pain a 7 13 14 14 Headache 7 8 9 9 Abdominal distension 3 7 9 8 Fatigue a 4 6 7 9 Eructation 1 6 8 8 Gastroesophageal reflux disease 2 6 6 7 Flatulence 2 5 6 6 Hair loss a 2 4 4 5 Gastrointestinal Adverse Reactions In a pool of Trials 1 and 2, gastrointestinal adverse reactions occurred more frequently among patients treated with once daily FOUNDAYO 5.5 mg (60%), 9 mg (68%), and 17.2 mg (69%) than placebo (37%). More patients treated with once daily FOUNDAYO 5.5 mg (3%), 9 mg (6%), and 17.2 mg (6%) discontinued treatment due to gastrointestinal adverse reactions than patients receiving placebo (0.7%). Of the FOUNDAYO-treated patients who reported GI adverse reactions, 60%, 36%, and 4% reported mild or moderate or severe adverse reactions, respectively. The incidence of nausea, vomiting, and diarrhea was higher during the FOUNDAYO dosage escalation period and decreased over time. Hypoglycemia In Trial 2, a trial of patients with type 2 diabetes and BMI ≥27 kg/m 2 , hypoglycemia (glucose <54 mg/dL) was reported in 2% of FOUNDAYO-treated patients versus 0.2% of placebo-treated patients. One patient treated with FOUNDAYO 5.5 mg once daily, and no patients receiving placebo reported severe hypoglycemia in Trial 2. In this trial, 7% of patients taking FOUNDAYO in combination with sulfonylurea reported hypoglycemia compared with 0.5% of patients not taking sulfonylurea. In Trial 1, a trial of FOUNDAYO in adults with BMI ≥27 kg/m 2 without type 2 diabetes, there was no systematic capturing of hypoglycemia, but glucose <54 mg/dL was reported in 0.6% of FOUNDAYO-treated patients and no placebo-treated patients. No patients in Trial 1 reported severe hypoglycemia. Other Adverse Reactions Acute Pancreatitis In a pool of Trials 1 and 2, 6 events of acute pancreatitis were confirmed by adjudication in 6 FOUNDAYO-treated patients (0.14 patients per 100 years of exposure) versus 2 events in 1 placebo-treated patient (0.04 patients per 100 years of exposure). Acute Kidney Injury In a pool of Trials 1 and 2, acute kidney injury was reported in 0.2% of FOUNDAYO-treated patients compared to 0.05% of placebo-treated patients. Hypotension In a pool of Trials 1 and 2, hypotension occurred more frequently among patients taking FOUNDAYO (2%) than patients taking placebo (0.5%). Hypotension was more frequently seen in FOUNDAYO-treated patients on concomitant antihypertensive therapy (4%) compared to FOUNDAYO-treated patients not on antihypertensive therapy (1%). Acute Gallbladder Disease In a pool of Trials 1 and 2, cholelithiasis was reported in 1% of FOUNDAYO-treated patients and 0.7% of placebo-treated patients, and acute cholecystitis was reported in 0.4% of FOUNDAYO-treated patients and 0.3% of placebo-treated patients. Tachycardia In a pool of Trials 1 and 2, tachycardia (tachycardia, heart rate increased, and sinus tachycardia) was reported in 3% of patients treated with FOUNDAYO and 0.9% receiving placebo. Treatment with FOUNDAYO resulted in a mean increase in heart rate of 4 to 5 beats per minute from baseline compared to 0.5 beat per minute with placebo. Hair Loss Hair loss adverse reactions in FOUNDAYO-treated patients were associated with weight reduction. In a pool of Trials 1 and 2, hair loss was reported more frequently in female than male patients in the FOUNDAYO (7% female versus 0.9% male) and placebo (3% female versus 0.7% male) treatment groups. Dizziness In a pool of Trials 1 and 2, dizziness was reported in 4% of FOUNDAYO-treated patients and 3% of placebo-treated patients. Dysgeusia In a pool of Trials 1 and 2, dysgeusia was reported in 0.9% of FOUNDAYO-treated patients and 0.3% of placebo-treated patients. Dysesthesia In a pool of Trials 1 and 2, dysesthesia was reported in 0.3% and 1% of patients treated with FOUNDAYO 9 mg, and 17.2 mg, respectively, and 0.1% of patients receiving placebo. No patients taking FOUNDAYO 5.5 mg reported dysesthesia. Hypersensitivity Reactions In a pool of Trials 1 and 2, hypersensitivity reactions, including anaphylactic reaction, occurred in 0.5% of FOUNDAYO-treated patients compared to 0.3% of placebo-treated patients. Laboratory Abnormalities Amylase and Lipase Increase In a pool of Trials 1 and 2, treatment with FOUNDAYO resulted in mean increases from baseline in serum pancreatic amylase concentrations of 16% to 20% and serum lipase concentrations of 26% to 31%, compared to mean increases from baseline in serum pancreatic amylase of 3% and serum lipase of 4% in placebo-treated patients. The clinical significance of elevations in amylase or lipase with FOUNDAYO is unknown in the absence of other signs and symptoms of pancreatitis. 6.2 Postmarketing Experience The following adverse reactions have been reported during post-approval use of GLP-1 receptor agonists. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal Disorders: acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death; ileus, intestinal obstruction, severe constipation including fecal impaction Hypersensitivity: anaphylaxis, angioedema Pulmonary : Pulmonary aspiration has occurred in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation Renal and Urinary Disorders: acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis
Clinical studies
14 CLINICAL STUDIES Overview of Trials 1 and 2 The effectiveness of FOUNDAYO has been established in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition based on adequate and well-controlled trials of an investigational orforglipron formulation (Trials 1 and 2), referred to in this section as FOUNDAYO. This section of labeling presents efficacy data from administration of the investigational orforglipron formulation shown as equivalent dosages of once daily FOUNDAYO [see Dosage and Administration ( 2.1 )] . FOUNDAYO was studied in two randomized, double-blind, placebo-controlled trials (Trials 1 and 2) in adults aged 18 years and older. In these trials, all patients received standard lifestyle intervention which included instruction on reduced-calorie diet and physical activity counseling (recommended minimum of 150 minutes/week) that began with the first dose of trial medication or placebo and continued throughout the trials. In Trial 1 patients were randomized in a 3:3:3:4 ratio to FOUNDAYO 5.5 mg once daily, 9 mg once daily, 17.2 mg once daily, or placebo once daily. In Trial 2 patients were randomized in a 1:1:1:2 ratio to FOUNDAYO 5.5 mg once daily, 9 mg once daily, 17.2 mg once daily, or placebo once daily. In Trials 1 and 2, dosages were titrated according to the dosage escalation described in Section 2.1 . In these trials, the primary efficacy parameter was mean percent change in body weight after 72 weeks of treatment. Trial 1 (NCT05869903) was a 72-week trial that enrolled 3,127 adult patients with obesity (BMI ≥30 kg/m 2 ), or with overweight (BMI 27 to <30 kg/m 2 ) and at least one weight-related comorbid condition, such as dyslipidemia, hypertension, obstructive sleep apnea, or cardiovascular disease; patients with type 2 diabetes were excluded. At baseline, mean age was 45 years (range 18 to 88 years), 64% were female, 56% were White, 28% were Asian, 9% were Black or African American, and 0.4% were American Indian/Alaska Native. A total of 38% were Hispanic or Latino ethnicity. Mean baseline body weight was 103.2 kg and mean BMI was 37 kg/m 2 . At baseline, 40% of patients had hypertension, 39% had dyslipidemia, 11% had obstructive sleep apnea, 1.4% had coronary artery disease, and 1.5% had cerebrovascular disease. Trial 2 (NCT05872620) was a 72-week trial that enrolled 1,613 adult patients with BMI ≥27 kg/m 2 and type 2 diabetes. Patients included in the trial had baseline HbA1c 7% to 10% and were treated with either diet and exercise alone, or any oral anti-hyperglycemic agent except dipeptidyl peptidase-4 (DPP-4) inhibitors or GLP-1 receptor agonists. Patients who were taking injectable glucose-lowering agents, including insulin, GLP-1 receptor agonists, or pramlintide were also excluded. At baseline, mean age was 57 years (range 20 to 92 years), 47% were female, 71% were White, 17% were Asian, 7% were Black or African American, and 0.3% were American Indian/Alaska Native. A total of 30% were Hispanic or Latino ethnicity. Mean baseline body weight was 101.4 kg, mean BMI was 35.6 kg/m 2 , and mean HbA1c was 8%. At baseline, 74% of patients had hypertension, 71% had dyslipidemia, 13% had obstructive sleep apnea, 7% had coronary artery disease, 5% had cerebrovascular disease, and 11% had diabetic retinopathy. Results for Trials 1 and 2 The proportions of patients who discontinued trial drug in Trial 1 were 22%, 22%, and 24% for the 5.5 mg, 9 mg, and 17.2 mg once daily FOUNDAYO-treated groups, respectively, and 30% for the placebo-treated group. The proportion of patients who discontinued trial drug in Trial 2 were 19%, 22%, and 20% for the 5.5 mg, 9 mg, and 17.2 mg once daily FOUNDAYO-treated groups, respectively, and 20% for the placebo-treated group. For Trials 1 and 2, the primary efficacy parameter was mean percent change in body weight from baseline to Week 72. After 72 weeks of treatment in Trials 1 and 2, there was a statistically significant reduction in body weight in the FOUNDAYO-treated groups compared with the placebo groups (see Table 6 ). A reduction in body weight was observed with FOUNDAYO regardless of age, sex, race, ethnicity, baseline BMI, and glycemic status. Table 6: Changes from Baseline in Body Weight at Week 72 in Trials 1 and 2 in Patients with Obesity or Overweight with ≥1 Weight-related Comorbid Condition Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; N = number of patients randomly assigned to trial drug. Note: Baseline mean is calculated using all randomized patients. a The intent-to-treat population consists of all randomized patients. For Trial 1 at Week 72, the body weight endpoint was missing for 24%, 16%, 14%, and 15% of patients randomized to placebo, FOUNDAYO 5.5 mg once daily, 9 mg once daily and 17.2 mg once daily, respectively. For Trial 2 at Week 72, the body weight endpoint was missing for 13%, 13%, 10%, and 7% of patients randomized to placebo, FOUNDAYO 5.5 mg once daily, 9 mg once daily and 17.2 mg once daily, respectively. Missing data were imputed from retrieved patients of the same randomized treatment group when the missingness was possibly related to trial treatment; otherwise, missing data were imputed using observed data from the same randomized treatment group (primary modified multiple imputation). b Unconditional average treatment effect estimated using ANCOVA adjusted for baseline value and other stratification factors. c p<0.001 (unadjusted 2-sided) compared to placebo for superiority; controlled for multiplicity. d Unconditional average treatment effect estimated using logistic regression adjusted for baseline value and other stratification factors. e Not controlled for multiplicity. Trial 1 (without diabetes) Trial 2 (with type 2 diabetes) Intent-to-Treat (ITT) Population a Placebo once daily N = 949 FOUNDAYO 5.5 mg once daily N = 723 FOUNDAYO 9 mg once daily N = 725 FOUNDAYO 17.2 mg once daily N = 730 Placebo once daily N = 630 FOUNDAYO 5.5 mg once daily N = 329 FOUNDAYO 9 mg once daily N = 332 FOUNDAYO 17.2 mg once daily N = 322 Body Weight Baseline mean (kg) 103.9 103.2 102.2 103.1 101.2 102.3 102.7 99.8 % Change from baseline b -2.1 -7.4 -8.3 -11.1 -2.5 -5.1 -7 -9.6 % difference from placebo (95% CI) b -5.3 (-6.1, -4.4) c -6.2 (-7.1, -5.3) c -9 (-10, -8.1) c -2.6 (-3.5, -1.6) c -4.5 (-5.4, -3.6) c -7.1 (-8.1, -6.1) c % of patients who lost ≥5% body weight 26.8 59.6 63.1 71.5 26.8 47.4 54.7 67 % difference from placebo (95% CI) d 32.7 (27.9, 37.6) c 36.3 (31.5, 41.1) c 44.7 (40, 49.3) c 20.6 (13.9, 27.3) c 27.9 (21.3, 34.5) c 40.2 (33.8, 46.6) c % of patients who lost ≥10% body weight 13 32.5 39.8 54.5 9.2 22.5 31.1 45.6 % difference from placebo (95% CI) d 19.4 (15.1, 23.7) c 26.8 (22.4, 31.1) c 41.4 (37, 45.9) c 13.3 (8.1, 18.5) c 21.9 (16.3, 27.5) c 36.4 (30.5, 42.3) c % of patients who lost ≥15% body weight 6 14.3 20.1 35.9 3.1 6.7 14.4 25.9 % difference from placebo (95% CI) d 8.3 (5.2, 11.4) c 14.1 (10.7, 17.6) c 29.8 (25.9, 33.7) c 3.6 (0.4, 6.8) e 11.3 (7.3, 15.3) c 22.8 (17.8, 27.8) c % of patients who lost ≥20% body weight 2.9 5.9 8.9 18.4 0.7 2.6 4.4 10.8 % difference from placebo (95% CI) d 3 (0.9, 5.2) e 6 (3.5, 8.4) c 15.5 (12.4, 18.6) c 1.8 (-0.2, 3.8) e 3.7 (1.4, 6) e 10.1 (6.6, 13.5) e The time courses of weight reduction from baseline with FOUNDAYO and placebo through Week 72 are depicted in Figure 1 for Trial 1 and Figure 2 for Trial 2. Figure 1: Change Over Time in Body Weight in Trial 1 in Patients with Obesity or Overweight with ≥1 Weight-related Comorbid Condition (without Type 2 Diabetes) Abbreviation: W72 TRE = treatment effect under treatment regimen estimand at Week 72. Displayed results are from randomized patients and treatment regimen estimand data points set. (1) Observed mean value from Week 0 to Week 72, and (2) model-based estimate ± standard error at Week 72 using primary modified multiple imputation. Figure 2: Change Over Time in Body Weight in Trial 2 in Patients with Obesity or Overweight and Type 2 Diabetes Abbreviation: W72 TRE = treatment effect under treatment regimen estimand at Week 72. Displayed results are from randomized participants and treatment regimen estimand data points set. (1) Observed mean value from Week 0 to Week 72, and (2) model-based estimate ± standard error at Week 72 using primary modified multiple imputation. The cumulative frequency distributions of percentage change in body weight are shown in Figure 3 for Trial 1 and Figure 4 for Trial 2. One way to interpret this figure is to select a change in body weight of interest on the horizontal axis and note the corresponding proportions of patients (vertical axis) in each treatment group who achieved at least that degree of weight reduction. For example, the vertical line arising from -10% in Figure 3 intersects the FOUNDAYO 17.2 mg once daily and placebo curves at approximately 55% and 13%, respectively, which correspond to the values shown in Table 6 . Figure 3: Changes in Body Weight (%) from Baseline to Week 72 in Trial 1 in Patients with Obesity or Overweight with ≥1 Weight-related Comorbid Condition (without Type 2 Diabetes) Note: Based on average percent weight change of each randomized patient within each specific treatment group from 100 imputed datasets including observed data and imputed data using the primary modified multiple imputation method for missing values. Figure 4: Changes in Body Weight (%) from Baseline to Week 72 in Trial 2 in Patients with Obesity or Overweight and Type 2 Diabetes Based on average percent weight change of each randomized patient within each specific treatment group from 100 imputed datasets including observed data and imputed data using the primary modified multiple imputation method for missing values. Figure 1 Figure 2 Figure 3 Figure 4 Effect of FOUNDAYO on Anthropometry and Cardiometabolic Parameters in Trials 1 and 2 Changes in waist circumference and cardiometabolic parameters with FOUNDAYO are shown in Table 7 for Trial 1 and Trial 2. Table 7: Changes from Baseline Anthropometry and Cardiometabolic Parameters at Week 72 in Trials 1 and 2 in Patients with Obesity or Overweight with ≥1 Weight-related Comorbid Condition Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; N = number of patients randomly assigned to trial drug. Note: Baseline mean is calculated using all randomized patients. For patients with missing baseline values, imputed values are used. a The intent-to-treat population consists of all randomized patients. Missing data were imputed from retrieved patients of the same randomized treatment group when the missingness was possibly related to trial treatment; otherwise, missing data were imputed using observed data from the same randomized treatment group (primary modified multiple imputation). b Unconditional average treatment effect estimated using ANCOVA adjusted for baseline value and other stratification factors. c p<0.001 (unadjusted 2-sided) compared to placebo for superiority; controlled for multiplicity. d Not controlled for multiplicity. e Baseline value is the geometric mean. f Analyzed using log-transformed data. Trial 1 (without diabetes) Trial 2 (with type 2 diabetes) Intent-to-Treat (ITT) Population a Placebo once daily N = 949 FOUNDAYO 5.5 mg once daily N = 723 FOUNDAYO 9 mg once daily N = 725 FOUNDAYO 17.2 mg once daily N = 730 Placebo once daily N = 630 FOUNDAYO 5.5 mg once daily N = 329 FOUNDAYO 9 mg once daily N = 332 FOUNDAYO 17.2 mg once daily N = 322 Waist Circumference (cm) Baseline mean 112.8 112.2 112 112.4 115 116.8 116.2 114.7 Change from baseline b -3.1 -7 -8.2 -10 -2.8 -5.4 -6.3 -8.3 Difference from placebo (95% CI) b -3.9 (-4.7, -3.1) c -5.1 (-5.9, -4.2) c -6.9 (-7.8, -6) c -2.6 (-3.5, -1.6) d -3.5 (-4.4, -2.6) d -5.5 (-6.5, -4.6) c Systolic Blood Pressure (mm Hg) Baseline mean 125.8 125.4 125.1 125.8 130.6 131.3 132.1 132.5 Change from baseline b -1.4 -5.7 -5.1 -6.4 -1.5 -4 -4.2 -4.6 Difference from placebo (95% CI) b -4.2 (-5.4, -3) d -3.7 (-4.8, -2.5) d -4.9 (-6.1, -3.8) d -2.5 (-4.1, -0.8) d -2.7 (-4.4, -1) d -3 (-4.8, -1.2) d Diastolic Blood Pressure (mm Hg) Baseline mean 81.8 81 81.2 80.9 81 81.6 82.1 81.8 Change from baseline b -1.4 -2.4 -2.3 -2.7 -1.3 -1.4 -1.4 -1.8 Difference from placebo (95% CI) b -0.9 (-1.7, -0.1) d -0.8 (-1.7, 0) d -1.2 (-2, -0.4) d -0.1 (-1.2, 0.9) d -0.1 (-1.2, 0.9) d -0.6 (-1.6, 0.5) d Pulse Rate (beats per minute) Baseline mean 73.7 73 73 73.5 74.2 75.9 73.7 74.6 Change from baseline b 0.6 3.6 3.9 4.6 0.4 2.8 3.9 3.6 Difference from placebo (95% CI) b 3.1 (2.2, 4) d 3.4 (2.5, 4.2) d 4.1 (3.1, 5) d 2.4 (1.3, 3.6) d 3.5 (2.4, 4.6) d 3.2 (2, 4.4) d HbA1c (%) Baseline mean 5.6 5.6 5.6 5.6 8 8 8.1 8.1 Change from baseline b -0.1 -0.3 -0.3 -0.3 -0.4 -1.2 -1.4 -1.7 Difference from placebo (95% CI) b -0.2 (-0.2, -0.2) d -0.2 (-0.2, -0.2) d -0.3 (-0.3, -0.2) d -0.8 (-1, -0.6) c -1 (-1.2, -0.8) c -1.2 (-1.4, -1.1) c Total Cholesterol (mg/dL) Baseline mean e 192.6 192.5 191.2 192.2 167.6 168 167.4 167.6 Percent change from baseline b -1.9 -3.4 -4.5 -4.3 -2.2 -1.5 -2 -4.9 Relative difference from placebo (95% CI) b -1.6 (-3.1, 0) d,f -2.7 (-4.2, -1.1) d,f -2.5 (-4, -0.9) d,f 0.7 (-2.2, 3.6) d,f 0.1 (-2.6, 2.9) d,f -2.7 (-5.3, -0.1) d,f Non-HDL Cholesterol (mg/dL) Baseline mean e 142.3 141.9 139.8 142.5 122.2 120.7 121.8 121 Percent change from baseline b -2 -5.4 -7 -7.7 -3 -4.3 -4.7 -9.7 Relative difference from placebo (95% CI) b -3.5 (-5.5, -1.4) d,f -5.1 (-7, -3.1) d,f -5.8 (-7.8, -3.8) d,f -1.3 (-5.1, 2.7) d,f -1.7 (-5.4, 2.1) d,f -6.9 (-10.2, -3.4) d,f LDL Cholesterol (mg/dL) Baseline mean e 114.4 115 113.3 114.6 84.7 84.3 84.1 85.3 Percent change from baseline b -1.6 -3.8 -5.5 -4.9 -3.1 -0.2 -0.7 -5.5 Relative difference from placebo (95% CI) b -2.2 (-4.5, 0.1) d,f -4 (-6.2, -1.7) d,f -3.3 (-5.5, -1) d,f 3.1 (-2.2, 8.6) d,f 2.5 (-2.1, 7.4) d,f -2.4 (-6.8, 2.2) d,f HDL Cholesterol (mg/dL) Baseline mean e 47.8 48.1 48.6 47 42 43.5 42.8 43.1 Percent change from baseline b -1 2.1 3.1 4.5 0.8 5.8 5.3 8 Relative difference from placebo (95% CI) b 3.1 (1.4, 4.8) d,f 4.1 (2.3, 5.8) d,f 5.5 (3.8, 7.2) d,f 5 (2.5, 7.6) d,f 4.4 (2.1, 6.8) d,f 7.2 (4.7, 9.7) d,f Triglycerides (mg/dL) Baseline mean e 125.3 121.1 119.2 125.6 162.4 157.8 164.4 157.2 Percent change from baseline b -4 -10.4 -13.1 -20 -4.1 -13.3 -14.7 -19.4 Relative difference from placebo (95% CI) b -6.7 (-9.9, -3.3) d,f -9.4 (-12.6, -6.1) d,f -16.6 (-19.5, -13.6) d,f -9.6 (-14.5, -4.4) d,f -11 (-15.6, -6.2) d,f -15.9 (-20.3, -11.3) d,f