The Effect of Exercise and Tirzepatide on Weight and Health Outcomes (EXER-MED)

The new type class of weight loss medications called GLP-1 medications have been shown to cause weight loss and improve risk factors for heart disease and diabetes. One thing that is currently unknown is whether exercise augments the impact of weight loss in people taking GLP-1 medication. The EXER-MED study is a pilot study evaluating the effect of 16 weeks of exercise training with GLP-1 medication compared to taking the medication alone. We will evaluate the impact of the study groups on weight, body composition (percent fat, percent lean mass), blood pressure, arterial stiffness, blood work (cholesterol, blood pressure, glucose, insulin) and quality of life.

Primary Outcome Measures

1. Weight
   Measurement will be taken 3 times and measured in kg. A positive value indicates an increase in weight and a negative value indicates a reduction in weight

Secondary Outcome Measures

1. Physical activity level
   Physical activity will measured via accelerometry (total steps and light, moderate, vigorous physical activity) and steps for 7 consecutive days
2. Changes in Blood Lipids Concentrations
   A fasting blood sample will be used to measure low density lipoprotein, high density lipoprotein, total cholesterol, and triglycerides will be measured. It will be quantified as the specific amount of the lipoprotein within the blood in mg/dL for all lipid variables. Participants will be fasted at least 12 hours prior to the blood draw. Change will be quantified as the week 16 value subtracted from the baseline value. A positive value indicates an increase in the blood lipid variable and a negative value is associated with a reduction in the variable.
3. Resting Metabolic Rate
   Resting metabolic rate (RMR) will be measured in a quiet, temperature-controlled room using indirect calorimetry with a clear ventilated canopy and dilution pump. An increase represents a positive change and a decrease represents a negative change
4. Change in Fasting Glucose Level
   Change in fasting glucose level. Fasting glucose level refers to the concentration of glucose within the blood (mg/dL). The change in fasting glucose level is quantified by subtracting the week 16 value from the baseline value. Thus, a positive value indicates an increase in glucose level and a negative value indicates a decrease in glucose.
5. Change in Fasting Insulin Level
   Fasting insulin represents the concentration of insulin in the blood. A positive value represents an increase in insulin concentration and a negative value represents a decrease in insulin concentration.
6. Change in Augmentation Index
   Central Arterial stiffness will be measured using a SphygmoCor XCEL (Itasca, IL). Participants will refrain from large meals and caffeine for at least 2 hours and alcohol, vigorous exercise and vasoactive medication for at least 12 hours. Testing will occur in a quiet temperature controlled room in the seated position after a 5 minute rest. Augmentation index represent central arterial stiffness and will be quantified via augmentation index (%). The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. A lower value indicates better stiffness
7. Changes in Blood Pressure (mmHg)
   Brachial and aortic blood pressure will be measured using a sphygmocor XCEL. Blood pressure is quantified in mmHg and will be taken in the seated position after a 5 minute rest. Change in blood pressure is quantified by subtracting the week 10 value from the baseline value. Thus, a positive number is associated with an increase in blood pressure across the time point and a decrease indicates a decrease in blood pressure
8. Change in hemoglobin A1C
   Hemoglobin A1C (%) will be measured at baseline and 16 weeks. Change in hemoglobin A1C will be determined by subtracting the week 16 value from baseline. A positive change indicates and increase in hemoglobin A1C and a negative value indicates a decrease in hemoglobin A1C.
9. Change in Waist Circumference
   Waist circumference will be measured at the natural waist (midway between the inferior border of the rib cage and the superior aspect of the iliac crest) with a gulick tape measure. Both landmarks (the inferior border of the ribcage and the superior aspect of the iliac crest) will be marked and the distance will be measured to determine the appropriate measurement site. Staff will confirm that: 1) the measurement tape remains horizontal; 2) the tape touches the entire circumference of the participant; 3) abdominal tissue is not compressed; 3) the tape measure is not within abdominal folds; 4) the measurement is taken at the end of normal respiration. The measurement will be repeated an additional time, and the reported value will be the average of these measurements. Both measurements must be within 0.5 cm to be considered acceptable for data purposes. The change in waist circumference will be quantified as the the week 16 value subtracted from the baseline value
10. Change in Body Composition (Fat mass or Lean Mass)
    Dual-energy X-ray absorptiometry will be used to measure changes in fat mass and lean mass. Body fat will be quantified as the percent of fat relative to the total body composition. Lean mass will be quantified as the percent of lean tissue relative to the total body composition. Change in these variables will be quantified as by subtracting the week 16 value from the baseline value. Thus, a change in positive direction is associated with an increase in body fat or lean mass and a negative value represent a decrease.
11. Change in Cardiorespiratory Fitness
    Fitness will be measured using a modified Balke protocol on a treadmill. Participants will walk at an initial speed of 2.0 mph with 0% grade for the first 3 minutes after which the treadmill speed will increase to 3.0 mph for the next 3 minutes. The treadmill grade will be increased by 2.5% every 3 minutes until volitional exhaustion. Fitness will be quantified in absolute terms (VO2) L/min, relative (VO2 mL/kg/min) and Estimated METs. Change in fitness will be quantified by subtracting the week 16 value from the baseline value. A positive value will indicate and increase in fitness. A negative value will indicate a reduction in fitness.
12. Change in dietary quality
    Dietary quality is measured with the ASA 24-hour dietary recall (ASA 24) . The ASA 24 is web-based tool that allows individuals to self-report all foods and beverages consumed in the previous 24 hours (i.e., the data collection method). This allows us to track diet quality changes over time. Change in dietary outcomes will be quantified by subtracting week 16 values from baseline. A positive value will represent an increase in a variable. A negative value will represent a reduction in a variable.
13. Quality of Life (IWQL-Lite)
    Measured by the questionnaire Impact of Weight on Quality of Life-Lite (IWQL-Lite) at baseline and Week 16. Scores range from 0 to 100, with 100 representing the best quality of life. Change in quality of life will be expressed by subtracting Week 16 from baseline level. An increase in quality of life will be represented by a positive value. A negative value represents a reduction in quality of life.
14. Change in isokinetic dynamometry
    Isokinetic knee flexor and extensor muscles strength and endurance will be evaluated with the isokinetic dynamometer. Change in strength and endurance outcomes will be quantified by subtracting the the Week 16 value from the baseline value. A positive value will indicate an increase in strength or endurance. A negative value will indicate a reduction in strength or endurance.