If I'm ineligible for GLP-1 (Glucagon-like peptide-1) injections and have tried Mysimba (Naltrexone-Bupropion) and Orlistat without success, what alternative weight management options are available in the UK?

Alternative Weight Management Options in the UK After Failed Mysimba and Orlistat

Your best remaining pharmacological option in the UK is phentermine monotherapy for short-term use (a few weeks), though you should also strongly consider bariatric surgery referral if you meet criteria, as this provides superior long-term outcomes compared to any remaining medication options. 1

Remaining Pharmacological Options

Phentermine (Short-term Use Only)

• Phentermine is available in the UK and represents your most effective remaining medication option, though it is approved only for short-term use (a few weeks) as an adjunct to lifestyle modification 1, 2
• The medication works as a sympathomimetic amine that suppresses appetite centrally, with dosing of 15-30 mg daily taken in the morning to avoid insomnia 2
• Weight reduction with phentermine is less robust than GLP-1 agonists but superior to orlistat, which you've already tried without success 1
• Late evening administration must be avoided due to risk of insomnia, and the medication can be taken with or without food 2

Critical contraindications to check before prescribing:

• History of cardiovascular disease (coronary artery disease, stroke, arrhythmias, heart failure, uncontrolled hypertension) 2
• Hyperthyroidism, glaucoma, agitated states, or history of drug abuse 2
• Current use or use within 14 days of monoamine oxidase inhibitors 2
• Even mild hypertension requires caution as blood pressure may increase 2

Diethylpropion (Alternative Short-term Option)

• Diethylpropion is another sympathomimetic amine available in the UK for short-term obesity management, with similar mechanism to phentermine but based on low certainty evidence 1, 3
• The medication is rapidly absorbed and extensively metabolized, with effects lasting 4-6 hours 3
• Dosing is typically 25 mg three times daily, though specific titration should be based on response and tolerability 3
• The same cardiovascular contraindications apply as with phentermine, and it should not be used in patients with severe hypertension 3

Important limitations of sympathomimetic agents:

• Tolerance to the anorectic effect typically develops within a few weeks, at which point the medication should be discontinued rather than increasing the dose 2
• These agents carry risk of abuse and dependence, so the least amount feasible should be prescribed at one time 2
• Both medications may impair ability to operate machinery or drive 2, 3

Bariatric Surgery Consideration

When to Refer for Surgical Evaluation

Bariatric surgery should be strongly considered as it provides superior and more durable weight loss compared to any pharmacological option, particularly given your failed trials of multiple medications 1

• Surgery is recommended for patients with BMI ≥30 kg/m² (or ≥27 kg/m² with weight-related complications) who do not achieve adequate response with lifestyle interventions and pharmacotherapy 1
• Metabolic surgery causes remission of type 2 diabetes in most cases and reduces cardiovascular and overall mortality risk compared to conventional therapies 1
• The safety profile of bariatric surgery compares favorably with other elective operations like hysterectomy or cholecystectomy, with cost-effectiveness ranging between $3,200-$13,000 per quality-adjusted life-year 1

Key point about timing:

• Delaying metabolic surgery reduces chances of diabetes remission, with remission rates dropping notably after 10 years of diabetes duration 1
• For patients with severe respiratory, cardiac, or renal complications of obesity, delayed surgery causes greater harm 1

Practical Implementation Strategy

Step 1: Cardiovascular Risk Assessment

• Obtain detailed cardiovascular history including any history of coronary disease, arrhythmias, stroke, or heart failure 2
• Measure blood pressure - even mild hypertension requires caution with sympathomimetic agents 2
• Screen for hyperthyroidism, glaucoma, and psychiatric conditions 2

Step 2: Medication Trial (If No Contraindications)

• Start phentermine 15 mg daily in the morning, taken with or without food 2
• Can increase to 30 mg daily if 15 mg is well-tolerated but insufficient 2
• Assess response at 12 weeks - if less than 5% weight loss achieved, discontinue the medication 4
• Plan for short-term use only (a few weeks) as tolerance develops and long-term efficacy is not established 2

Step 3: Concurrent Bariatric Surgery Referral

• Initiate referral for bariatric surgery evaluation simultaneously with medication trial, as waiting times can be substantial and surgery provides superior long-term outcomes 1
• This is particularly important if you have type 2 diabetes, as earlier surgery improves remission rates 1

Critical Caveats

The fundamental limitation you face is that the most effective weight-loss medications (GLP-1 agonists like semaglutide 2.4 mg and liraglutide 3.0 mg) are unavailable to you, and these produce 15-21% weight loss compared to the modest effects of remaining options 1, 5

• Phentermine and diethylpropion are approved only for short-term use, not the long-term management that obesity requires as a chronic disease 2, 6
• Orlistat, which you've already tried, is actually suggested against by the American Gastroenterological Association due to modest efficacy and significant gastrointestinal side effects 1
• Naltrexone/bupropion (Mysimba), which you've also tried, represents one of the better non-GLP-1 options, so its failure suggests limited benefit from remaining pharmacological approaches 1

Given these limitations, bariatric surgery becomes increasingly important as your most effective remaining option for achieving meaningful, sustained weight loss and improvement in obesity-related comorbidities. 1