What supplements and medications, apart from Ozempic (semaglutide), can aid in fat loss?

Medications and Supplements for Fat Loss Beyond GLP-1 Receptor Agonists

FDA-Approved Medications for Weight Loss

Phentermine is the primary FDA-approved medication alternative to GLP-1 agonists for short-term weight management, though it carries significant cardiovascular risks and abuse potential. 1

Phentermine (Short-Term Use Only)

• Phentermine is FDA-approved as a short-term adjunct (a few weeks) for weight reduction in patients with BMI ≥30 kg/m² or BMI ≥27 kg/m² with risk factors like hypertension, diabetes, or hyperlipidemia. 1
• The usual adult dose is 15-30 mg approximately 2 hours after breakfast, with late evening dosing avoided due to insomnia risk. 1
• For patients with severe renal impairment (eGFR 15-29 mL/min/1.73 m²), the maximum dose is 15 mg daily; avoid use entirely in end-stage renal disease. 1

Critical Safety Concerns with Phentermine

• Phentermine is absolutely contraindicated in patients with cardiovascular disease (coronary artery disease, stroke, arrhythmias, heart failure, uncontrolled hypertension), hyperthyroidism, glaucoma, or history of drug abuse. 1
• Primary pulmonary hypertension (PPH)—a rare, frequently fatal lung disease—has been reported with phentermine use, particularly when combined with fenfluramine or dexfenfluramine, though cases have occurred with phentermine alone. 1
• Serious regurgitant cardiac valvular disease affecting the mitral, aortic, and tricuspid valves has been reported, and the association with phentermine alone cannot be ruled out. 1
• Phentermine is chemically and pharmacologically related to amphetamine and carries significant abuse and dependence potential. 1
• The safety and efficacy of combining phentermine with any other weight loss products (prescription, over-the-counter, herbal, or serotonergic agents like SSRIs) have not been established and are not recommended. 1

When Tolerance Develops

• When tolerance to phentermine's appetite-suppressing effect develops, the dose should NOT be increased; instead, the drug must be discontinued. 1

Lifestyle Modifications: The Foundation of Weight Loss

Comprehensive lifestyle modification remains the cornerstone of sustainable weight loss, achieving approximately 10% weight reduction in 16-26 weeks when properly implemented. 2

Evidence-Based Lifestyle Interventions

• A caloric deficit of 500 kcal below daily requirements, combined with minimum 150 minutes/week of physical activity, forms the foundation of any weight loss program. 3
• Resistance training should be incorporated to preserve lean body mass during weight loss, particularly important when using any pharmacotherapy. 3
• Long-term weight control is facilitated by continued patient-therapist contact, whether provided in person, by telephone, mail, or e-mail. 2
• High levels of physical activity and consumption of low-calorie, portion-controlled meals, including liquid meal replacements, help maintain weight loss long-term. 2

Supplements: Limited Evidence

No supplements have FDA approval or strong clinical evidence for fat loss comparable to prescription medications. The evidence base for dietary supplements in weight management is substantially weaker than for prescription medications, and most lack rigorous clinical trial data demonstrating efficacy for fat loss.

Critical Considerations

• Combining supplements with prescription weight loss medications has not been studied for safety or efficacy and is not recommended. 1
• Patients should be counseled that over-the-counter supplements are not regulated with the same rigor as prescription medications and may have undisclosed ingredients or drug interactions.

Clinical Decision Algorithm

For Patients Seeking Non-GLP-1 Options:

1. First-line approach: Implement comprehensive lifestyle modification with 500 kcal deficit, ≥150 minutes/week physical activity, and resistance training. 3, 2

2. If lifestyle modification alone is insufficient after 3-6 months AND patient has no cardiovascular disease, hyperthyroidism, glaucoma, or substance abuse history: Consider phentermine 15-30 mg for SHORT-TERM use only (a few weeks). 1

3. If patient has ANY cardiovascular disease, uncontrolled hypertension, hyperthyroidism, glaucoma, or history of substance abuse: Phentermine is contraindicated; refer back to GLP-1 agonists or consider bariatric surgery consultation if BMI criteria are met. 1

4. Monitor phentermine patients closely for signs of pulmonary hypertension (dyspnea, angina, syncope, lower extremity edema) and discontinue immediately if these develop. 1

5. When phentermine tolerance develops or after short-term use period: Discontinue medication and reassess need for GLP-1 agonist therapy or bariatric surgery. 1

Common Pitfalls to Avoid

• Never combine phentermine with other weight loss medications, supplements, or SSRIs—safety has not been established. 1
• Never increase phentermine dose when tolerance develops—this increases cardiovascular and abuse risks without additional benefit. 1
• Never prescribe phentermine for long-term use—it is FDA-approved only for short-term (a few weeks) therapy. 1
• Never overlook cardiovascular screening before initiating phentermine—undiagnosed cardiovascular disease is an absolute contraindication. 1
• Do not rely on supplements as primary weight loss therapy—evidence is insufficient and they lack regulatory oversight. 1

Why GLP-1 Agonists Remain Superior

For context, semaglutide 2.4 mg achieves 14.9% weight loss at 68 weeks with proven cardiovascular benefits (20% reduction in cardiovascular death, MI, or stroke), while tirzepatide achieves 20.9% weight loss—far exceeding what phentermine or lifestyle modification alone can accomplish. 3, 4, 5, 6 Oral semaglutide 25 mg achieves 13.6% weight loss at 64 weeks, providing a non-injectable alternative. 7