Clinical Research Directory

Inclusion Criteria: * BMI 30-44.9 kg/m2 or BMI 27-29.9 with weight related comorbidity (including hypertension, prediabetes, type 2 diabetes mellitus, dyslipidemia, nonalcoholic fatty 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 schedule for 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 1 month prior to randomization and agreement to use such a method during study participation and for an additional 8 weeks after the end of study drug administration * Provision of electronically-signed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study Exclusion Criteria: * History of coronary artery, cerebrovascular or peripheral arterial disease including myocardial infarction, unstable angina, revascularization, stroke/TIA, carotid intervention, 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 for glaucoma * Heavy alcohol use within the last 6 months (men: more than 4 drinks on any day or more than 14 drinks per week; women: more than 3 drinks on any day or more than 7 drinks per week) * History of substance use disorder or active use of illicit substances within the last 12 months. Tetrahydrocannabinol (THC)-containing products will not be considered 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 24 months; 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 visit or 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, bipolar disorder, severe depression) * Binge Eating Disorder, Bulimia or Anorexia Nervosa diagnosis or treatment within the last 2 years * Prior procedure for weight control (including bariatric surgery, devices) * Use of phentermine, phentermine-containing medication, or anti-obesity medication with similar mechanism of action to phentermine (e.g., phendimetrazine or diethylpropion) in the previous 24 months * Use of any non-phentermine-containing medications prescribed for weight loss in previous 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 GLP1 agonist or SGLT2 inhibitor in patients with diabetes; use of topiramate among patients 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 current body 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 changes and/or study medication or has participated in such a study within the last 12 months * Total body weight that exceeds 400 lbs., precluding use of the digital scale in the lifestyle intervention * Upper arm circumference that exceeds 50 cm, precluding use of the OMRON HEM 907 XL to measure blood pressure * Other concern or medical comorbidity that, per discretion of study clinician, would render the participant unfit or unable to safely take part in the 24-month intervention