Long-term Effectiveness of the Antiobesity Medication Phentermine

Inclusion Criteria:

• BMI 30-44.9 kg/m2 or BMI 27-29.9 with weight related comorbidity (includinghypertension, prediabetes, type 2 diabetes mellitus, dyslipidemia, nonalcoholicfatty liver disease, treated obstructive sleep apnea, osteoarthritis, low back pain,gastroesophageal reflux disease)

• English-speaking

• Has a smartphone or other device with regular internet access

• Interested in and willing to lose weight as a result of treatment

• Able to take oral medication and willing to adhere to the clinical visit schedulefor the trial and lifestyle based treatment regimen throughout the study duration,as recommended by the study clinician

• For females of reproductive potential: use of effective contraception for at least 1month prior to randomization and agreement to use such a method during studyparticipation and for an additional 8 weeks after the end of study drugadministration

• Provision of electronically-signed consent form

• Stated willingness to comply with all study procedures and availability for theduration of the study

Exclusion Criteria:

• History of coronary artery, cerebrovascular or peripheral arterial disease includingmyocardial infarction, unstable angina, revascularization, stroke/TIA, carotidintervention, claudication

• Poorly-controlled blood pressure (>149/94) or elevated heart rate (>110 bpm)

• History of cardiac arrhythmia

• Active / currently-treated hyperthyroidism

• History of glaucoma or been told by an ophthalmologist that you are at high risk forglaucoma

• Heavy alcohol use within the last 6 months (men: more than 4 drinks on any day ormore than 14 drinks per week; women: more than 3 drinks on any day or more than 7drinks per week)

• History of substance use disorder or active use of illicit substances within thelast 12 months. Tetrahydrocannabinol (THC)-containing products will not beconsidered an illicit substance.

• Use of a drug in the monoamine oxidase inhibitor class, currently or within the last 14 days

• Currently pregnant or lactating/breastfeeding; intention to get pregnant in next 24months; seeking or in active treatment for infertility

• End-stage renal disease on dialysis or CKD class IV or higher (eGFR <30)

• History of valvular heart disease

• Congestive heart failure (any history or current)

• Cirrhosis or symptoms of liver failure in the last 2 years

• Severe pulmonary disease requiring supplemental oxygen

• Quit using nicotine-containing products less than 6 months prior to baseline visitor intention to quit use in the next 2 years

• Use of oral corticosteroids more than 5 days/month in the last 3 months

• Elevated depressive symptoms

• Uncontrolled anxiety symptoms

• Hospitalization for mental illness in the last 24 months

• Diagnosis of dementia or serious mental illness (e.g., schizophrenia, bipolardisorder, severe depression)

• Binge Eating Disorder, Bulimia or Anorexia Nervosa diagnosis or treatment within thelast 2 years

• Prior procedure for weight control (including bariatric surgery, devices)

• Use of phentermine, phentermine-containing medication, or anti-obesity medicationwith similar mechanism of action to phentermine (e.g., phendimetrazine ordiethylpropion) in the previous 24 months

• Use of any non-phentermine-containing medications prescribed for weight loss inprevious 12 months

• Unstable dose of weight-loss-promoting medications within the last 12 months.Weight-loss-promoting medications are medication prescribed for another condition,but are known to have weight loss effects. Examples would include use of a GLP1agonist or SGLT2 inhibitor in patients with diabetes; use of topiramate amongpatients with migraine headaches.

• Use of any stimulant medications in previous 12 months

• Known allergy or intolerance to phentermine or phentermine-containing medication

• Documented or self-reported weight change (gain or loss) of more than 5% of currentbody weight in the past 3 months

• History of cancer other than non-melanoma skin cancer in the past 5 years

• History of organ transplantation

• Plan to move outside the area in the next two years

• Unable to make changes to diet (e.g., severe food allergies or intolerances;medically necessary aspects of diet incompatible with intervention)

• Already participating in another research study that includes lifestyle changesand/or study medication or has participated in such a study within the last 12months

• Total body weight that exceeds 400 lbs., precluding use of the digital scale in thelifestyle intervention

• Upper arm circumference that exceeds 50 cm, precluding use of the OMRON HEM 907 XLto measure blood pressure

• Other concern or medical comorbidity that, per discretion of study clinician, wouldrender the participant unfit or unable to safely take part in the 24-monthintervention