What is the optimal resistance‑training regimen for an adult with antipsychotic‑induced weight gain (e.g., olanzapine, clozapine, quetiapine) who is initiating metformin?

Resistance Training for Olanzapine-Induced Weight Gain

For adults with antipsychotic-induced weight gain initiating metformin, perform resistance training 2-3 times per week on non-consecutive days, targeting all major muscle groups with at least one set of 5 or more different exercises, combined with 150-300 minutes per week of moderate-intensity aerobic activity. 1

Evidence-Based Resistance Training Protocol

Frequency and Structure

• Resistance training should be performed 2-3 sessions per week on non-consecutive days to allow adequate recovery while maximizing lean muscle preservation during weight loss 1
• Each session should include at least one set of 5 or more different resistance exercises involving large muscle groups (legs, back, chest, shoulders, arms) 1
• Sessions can utilize free weights, weight machines, or bodyweight exercises—any intensity of resistance training improves strength and metabolic outcomes, though heavier resistance may provide superior glycemic control 1

Specific Exercise Selection

Target these major muscle groups in each session 1:

• Lower body: squats, leg press, lunges, leg curls
• Upper body pushing: chest press, shoulder press, push-ups
• Upper body pulling: rows, lat pulldowns, pull-ups
• Core: planks, dead bugs, bird dogs

Integration with Aerobic Exercise

• Combine resistance training with 150-300 minutes per week of moderate-intensity aerobic exercise (50-70% of maximal heart rate), which produces an additional 2-3 kg weight loss beyond resistance training alone 1
• Aerobic activity can be accumulated in bouts of at least 10 minutes throughout the day 1
• Break up sedentary time every 30 minutes with brief standing or walking to further improve metabolic outcomes 1

Physiological Rationale

Resistance training specifically preserves lean/fat-free mass during weight loss, which is critical because olanzapine-induced weight gain is primarily adipose tissue rather than muscle 1. This preservation of muscle mass:

• Maintains resting metabolic rate during caloric restriction
• Improves insulin sensitivity independent of weight loss 1
• Enhances functional capacity and activities of daily living 1

Metformin Adjunctive Therapy Context

Since you are initiating metformin (target dose 1000 mg total daily), the combination approach is optimal 1:

• Metformin produces mean weight loss of 3.27 kg (95% CI: -4.66 to -1.89 kg) when used to counteract antipsychotic-induced weight gain 1
• Start metformin at 500 mg once daily, increase by 500 mg every 2 weeks up to 1 g twice daily (use modified-release formulation if available to minimize GI side effects) 1
• Assess renal function before starting metformin and avoid in renal failure; monitor annually with liver function, HbA1c, renal function, and vitamin B12 1

Monitoring and Progression

Initial Phase (Weeks 1-6)

• Monitor weight weekly and watch for unintentional weight gain >2 kg in a month or ≥7% increase from baseline 1
• Assess baseline BMI, waist circumference, blood pressure, HbA1c, glucose, and lipids before starting the exercise program 1
• Progress resistance training intensity gradually—increase weight/resistance when current load becomes manageable for 12-15 repetitions 1

Maintenance Phase (After 3 Months)

• Repeat metabolic assessments at 3 months: BMI, waist circumference, blood pressure, fasting glucose (re-check at 4 weeks), and lipids 1
• Continue annual monitoring thereafter 1
• Maintain exercise regimen indefinitely—physical activity is essential for weight maintenance even after initial weight loss 1

Common Pitfalls to Avoid

• Do not rely on exercise alone for weight loss—physical activity has modest weight loss effects (2-3 kg) and must be combined with dietary modification and metformin for optimal results 1
• Do not allow more than 2 days between exercise sessions, as this reduces the insulin-sensitizing effects of physical activity 1
• Do not prescribe very low-calorie diets (<800 kcal/day) without close medical supervision—these require specialized monitoring 1
• Do not neglect dietary counseling—portion control, reduction of ultra-processed foods, and increased fruit/vegetable intake are essential adjuncts 1

Alternative Considerations if Inadequate Response

If weight loss remains inadequate after 8-12 weeks of combined metformin, resistance training, aerobic exercise, and dietary modification 1:

• Consider adding topiramate 100 mg/day (mean weight loss 3.76 kg; 95% CI: -4.92 to -2.69 kg) 1
• Evaluate for GLP-1 receptor agonist therapy if BMI ≥27 with weight-related complications 1
• Reassess antipsychotic choice—switching to an agent with lower metabolic liability (aripiprazole, ziprasidone) may be appropriate if psychiatric stability allows 1, 2