What are the benefits and considerations of resistance training in patients with type 2 diabetes on GLP-1 (Glucagon-Like Peptide-1) receptor agonist medication, such as liraglutide (Victoza) or semaglutide (Ozempic)?

Resistance Training in Patients on GLP-1 Medications

Patients with type 2 diabetes on GLP-1 receptor agonists should perform resistance training 2-3 sessions per week on non-consecutive days, as this combination is particularly critical to preserve muscle mass during the substantial weight loss these medications produce while simultaneously optimizing glycemic control. 1

Why Resistance Training is Essential with GLP-1 Therapy

The combination of GLP-1 receptor agonists with resistance training addresses a critical concern: GLP-1 medications like semaglutide and tirzepatide cause significant weight loss (mean 8.47 kg with tirzepatide) that includes loss of both fat mass and lean body mass, raising concerns about development or worsening of frailty and sarcopenic obesity. 1, 2 Supervised exercise combined with GLP-1 therapy is more favorable in maintaining body weight and body composition compared with GLP-1 therapy alone. 1

Resistance training of any intensity improves strength, balance, and ability to engage in activities of daily living throughout the lifespan, directly counteracting the muscle loss associated with GLP-1-induced weight reduction. 1

Specific Resistance Training Protocol

Frequency and Timing

• Perform resistance training at least 2-3 days per week on non-consecutive days. 1, 3
• Never allow more than 2 consecutive days without exercise, as insulin resistance returns within 48-72 hours of the last exercise session. 1

Exercise Selection

• Include 5-10 exercises involving major muscle groups in the upper body, lower body, and core. 1, 3
• Use multi-joint compound movements (chest press, rows, squats, leg press, shoulder press, lat pulldown, leg curls, leg extensions, core exercises) to maximize whole-body insulin sensitivity improvements. 3

Intensity and Volume

• Start at moderate intensity (50% of 1-repetition maximum) and progress to vigorous intensity (75-80% of 1-RM) for optimal gains in strength and insulin action. 1, 3
• Perform 10-15 repetitions to near fatigue per set initially, progressing over time to heavier weights that can be lifted only 8-10 times. 1, 3
• Complete a minimum of 1 set per exercise, progressing to 3-4 sets for optimal strength gains. 1, 3
• Studies show programs with multiple sets (≥21 sets per week) are associated with larger effect sizes for glycemic control. 4

Progression Strategy

• Increase weight/resistance first, only after consistently exceeding the target number of repetitions per set. 1, 3
• Then increase the number of sets, and finally increase training frequency if needed. 1, 3
• Progress slowly over 6 months to thrice-weekly sessions of three sets of 8-10 repetitions at 75-80% of 1-RM on 8-10 exercises as the optimal goal. 1

Combining with Aerobic Exercise

The combination of resistance training with at least 150 minutes per week of moderate-intensity aerobic exercise spread over at least 3 days produces superior glycemic control compared to either modality alone. 1, 5 Clinical trials provide strong evidence that combined aerobic and resistance exercise in adults with type 2 diabetes has an additive benefit, with structured exercise durations exceeding 150 minutes per week associated with A1C reductions of 0.89%. 1, 5

Break up all sitting periods exceeding 30 minutes with brief standing, walking, or light activity for additional glycemic benefits. 1, 5

Mechanisms of Benefit

Resistance training increases GLUT4 translocation in skeletal muscle, increases insulin sensitivity, and restores metabolic flexibility. 6 Both aerobic and resistance training improve insulin action, blood glucose control, and fat oxidation and storage in muscle, with resistance exercise specifically enhancing skeletal muscle mass. 1, 6

Heavier weights or resistance may be needed for optimization of insulin action and blood glucose control. 1 Resistance training promotes health benefits through increased skeletal muscle mass and qualitative adaptations, such as enhanced glucose transport and mitochondrial oxidative capacity. 7

Safety Considerations with GLP-1 Medications

Hypoglycemia risk is low with GLP-1 receptor agonists when used without insulin or insulin secretagogues, so patients generally do not need to postpone exercise due to elevated blood glucose (even up to 300 mg/dL without ketosis), provided they are feeling well and adequately hydrated. 1, 3

Initial instruction and periodic supervision by a qualified exercise trainer is recommended, particularly for resistance training, to ensure optimal benefits to glucose control, blood pressure, lipids, cardiovascular risk, and to minimize injury risk. 1, 3 Supervised training produces greater compliance and blood glucose control than unsupervised exercise. 3

Patient Selection Considerations

Resistance training produces larger effect sizes in patients with diabetes of relatively short duration (<6 years) or high baseline HbA1c (≥7.5%), while smaller effects are seen in patients with particularly high baseline BMI (≥32 kg/m²). 4 Each increment of 1% in baseline HbA1c enlarges the effect size by 0.036%, while each increment of 1 kg/m² in baseline BMI decreases it by 0.070%. 4

Critical Implementation Points

• Free weights, resistance machines, elastic bands, or body weight as resistance all produce fairly equivalent gains in strength and mass of targeted muscles. 1
• Resistance training of any intensity is recommended—even lighter resistance training improves outcomes, though heavier weights optimize insulin action. 1
• The positive effects of exercise on GLP-1 levels themselves have been reported, suggesting a synergistic relationship between physical activity and GLP-1 pharmacotherapy. 8