Effect of Metformin, a Drug Used to Treat Diabetes, vs Placebo

Study Overview
=================
Brief Summary
-----------------
Metformin is a drug used to treat patients with diabetes. The aim of this study is to examine the effect of Metformin along with a low-calorie diet on obese and/or overweight adults with an increased waist measurement. In addition, the study also aims to look at the effect of the drug vs. placebo on quality of life and physical activity.

Detailed Description
-----------------
Obesity is a growing epidemic in the United States. Weight gain is associated with an increased risk of developing life-threatening conditions such as high blood pressure or diabetes. Therefore, there is great interest in developing non-invasive treatments to help combat obesity. Currently, there are only few weight-loss drugs available for the treatment of obesity. In the more recent past, GLP-1 analogues (a type of non-insulin medication used to treat patients with diabetes) are being promoted as a new strategy to lose weight without major side effects however, with high costs and challenging supply chain issues. This is a double-blinded, randomized study. This means that participants will be assigned to one of two groups. Participants will have a 1:1 chance of being assigned to receive either the study drug or a placebo (a capsule that does not contain the active ingredients). This assignment will be determined by chance. The process is similar to drawing cards or picking straws. This means your assignment to one of the groups is based on chance and not a medical decision made by the study doctor. In addition, neither participants nor the investigators will know what groups participants have been assigned to. During this study, your participation will last up to 26 weeks (including screen) with a total of 8 clinic visits. Participants will undergo a total of 5 blood draws, blood samples will be taken at screen baseline and weeks 8, 16 and 24.

Official Title
-----------------
Effect of Metformin ER With Hypocaloric Diet on Weight Loss in Overweight/Obese Patients With Increased Waist Circumference

Conditions
-----------------
NIDDM, Obesity

Intervention / Treatment
-----------------
* Drug: Metformin Extended Release (ER) Oral Tablet
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, age ≥ 18 years at the time of signing informed consent. Body Mass Index (BMI) ≥ 27 kg/m2 Waist circumference >40 for men, and >35 for women Exclusion Criteria: A self-reported change in body weight > 5 kg (11 lbs) within 90 days before screening irrespective of medical records Diagnosed with T2D (HbA1c >7.5 (53 mmol/mol) Current use of insulin or oral medication of metformin, SU, SGLT2i, glitazone, DPP4 or GLP-1 agonist injections as single agent therapy or combination oral agents. Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of < 45 mL/min/1.73 m2 (< 60 ml/min/1.73 m2 in subjects treated with SGLT2i) according to CKDEPI creatinine equation as defined by KDIGO 201242 by the central laboratory at screening History of thyroid disease, but not taking medication or medication dosage changed one or more times over last 6 months (History of thyroid disease and on a stable dose of prescription medication for 6 months or longer is acceptable). History or lactic acidosis Liver problems Congestive heart failure History of alcoholism Recent surgery Heart attack, severe infection or stroke Any unstable medical conditions or terminal diagnosis Pregnancy or lactation Allergy and intolerance to metformin

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, single-blind, controlled trial. All eligible participants will be randomly assigned to placebo or Metformin.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin Extended Release (ER) Oral Tablets<br>This is a 24-week, randomized, double-blinded, two arm parallel clinical trial comparing metformin ER vs. placebo in combination with a hypocaloric diet (-500 kcal/day). 150 individuals with obesity and increased waist circumference will be randomized to taking metformin ER with hypocaloric diet or placebo with hypocaloric diet. All patients will receive dietary and exercise counseling with the intent of reducing their average caloric intake by 500 kcal/day. | Drug: Metformin Extended Release (ER) Oral Tablet<br>* Metformin ER will be provided as 1000 mg capsules by Qingdao Baheal Pharmaceutical Co., Ltd. In addition to the active ingredient metformin HCl,each tablet contains the following inactive ingredients: Povidone, Sodium Lauryl Sulfate, Magnesium Stearate, Cellulose Acetate, Polyethylene Glycol (PEG 400, PEG 8000), Triacetin, Hypromellose, Titanium Dioxide, Polysorbate 80, Ferrosoferric Oxide, Shellac.<br>|
| Placebo Comparator: Placebo<br>Patients in the placebo arm will be randomized to placebo with hypocaloric diet. All patients will receive dietary and exercise counseling with the intent of reducing their average caloric intake by 500 kcal/day. | Drug: Placebo<br>* Matching placebo will be provided as 1000 mg capsules<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who achieve body weight reduction ≥5% from baseline | Percent change in body weight reduction ≥5% from baseline (week 0) to week 24. | 24 Weeks | 
| Change in total body weight from baseline | Percent change in total body weight (TBW) from baseline (week 0) to week 24 in body weight. | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total Body Mass Index (BMI) from baseline | Change from baseline (week 0) to week 24 in: BMI | 24 Weeks | 
| Change in insulin sensitivity from baseline | Change from baseline (week 0) to week 24 in Insulin sensitivity | 24 Weeks | 
| Change in fasting blood lipids from baseline | Change from baseline (week 0) to week 24 in Fasting blood lipids | 24 Weeks | 
| Change in waist circumference from baseline | Change from baseline (week 0) to week 24 in:Waist circumference (cm) | 24 weeks | 
| Percent change in % body fat from baseline | Change from baseline (week 0) to week 24 in: body fat (%). | 24 weeks |