What is the treatment for a 68-year-old man with declined muscle mass due to taking Zepbound (tirzepatide) who experiences tremendous muscle pain and soreness with light exercise?

Treatment for Tirzepatide-Associated Muscle Pain and Sarcopenia

Immediately discontinue tirzepatide and initiate a structured resistance training program combined with adequate protein intake to address the muscle loss and exercise-induced pain. 1, 2

Immediate Management

Discontinue Tirzepatide

• Stop tirzepatide immediately as it is directly associated with significant muscle mass loss (approximately 34% of total weight loss is muscle) and has been linked to rhabdomyolysis and necrotizing myopathy 1, 2
• The muscle pain with light exercise suggests possible drug-induced myopathy or rhabdomyolysis, which requires urgent evaluation 1

Diagnostic Workup

• Measure creatine kinase (CK), aldolase, AST, ALT, and LDH to evaluate for rhabdomyolysis or myositis 3
• Check inflammatory markers (ESR, CRP) to assess muscle inflammation 3
• Obtain urinalysis to screen for myoglobinuria if rhabdomyolysis is suspected 3, 1
• If CK is elevated ≥3 times upper limit of normal with muscle weakness or severe pain, consider urgent hospitalization 3

Symptomatic Pain Management

For Mild to Moderate Pain (Grade 1-2)

• Initiate scheduled acetaminophen as first-line analgesia for musculoskeletal pain in elderly patients 3
• NSAIDs may be used cautiously if no contraindications (avoid in patients with heart failure, hypertension, or kidney disease) 3
• If CK is elevated with muscle weakness, initiate prednisone 0.5-1 mg/kg daily 3

For Severe Pain (Grade 3-4)

• Consider hospitalization if severe weakness limits mobility 3
• Initiate prednisone 1 mg/kg daily or methylprednisolone IV 1-2 mg/kg for severe cases 3
• Urgent rheumatology or neurology consultation 3

Long-Term Muscle Recovery Strategy

Resistance Training Protocol

• Prescribe progressive resistance training (PRT) as the primary treatment for sarcopenia - this is the reference standard for age-related and disease-related muscle loss 3
• Begin with low resistance (40-60% of one-repetition maximum) using major muscle groups 3
• Start with 2-3 repetitions if pain limits activity, gradually progressing to 10-12 repetitions, 2-3 days per week 3
• Focus on functional exercises including sit-to-stand, stair climbing, and weight-bearing activities 3
• Use pain threshold as intensity guide initially 3

Aerobic Exercise Component

• Add moderate-intensity aerobic exercise (walking, cycling) for 30-45 minutes, 5-7 days per week to improve overall function and quality of life 3
• Start with brief 10-minute sessions, adding 5 minutes per session until 30 minutes is reached 3

Nutritional Support

• Ensure adequate protein intake to support muscle recovery and prevent further sarcopenia 3
• Maintain healthy weight through Mediterranean-style diet rather than restrictive low-calorie diets, which can worsen muscle loss 3

Critical Pitfalls to Avoid

• Do not restart tirzepatide - the proportional muscle loss (15% reduction in both weight and muscle mass) and association with rhabdomyolysis make continuation unsafe 1, 2
• Do not attribute all symptoms to normal aging - tirzepatide-induced necrotizing myopathy has been documented and requires specific evaluation 1
• Avoid restrictive diets in this catabolic state, as they will worsen muscle loss and micronutrient deficiencies 3
• Do not use opioids for musculoskeletal pain in elderly patients due to cognitive impairment, falls, and addiction risks 3

Monitoring and Follow-Up

• Repeat CK, muscle enzymes, and inflammatory markers weekly until normalized 3
• Physical therapy assessment every 4 months to monitor muscle strength, function, and exercise progression 3
• Consider EMG or MRI if symptoms persist despite conservative management to rule out ongoing myopathy 3
• Monitor for improvement in functional measures: timed 10-meter walk, Gowers' maneuver, stair climbing ability 3