How effective is rejoining a long-term weight loss program? The 5- and 10-year MRI-assessed Follow Interventions Trial (FIT) project

It remains unclear whether reengaging in lifestyle weight loss interventions is effective for the long-term. We conducted the CENTRAL (trial 1, T1) lifestyle weight-loss trial in 2012–2014, and the DIRECT-PLUS (trial 2, T2) weight-loss trial in 2017–2018. All participants were invited for follow-up in 2022–2024 to assess weight, metabolic biomarkers, and fat depots via magnetic-resonance-imaging (MRI) five years after the second trial. The analysis included 572 trial observations contributed by 480 participants; of these, 388 participated in one of the two trials and 92 participated in both (T1 + T2 rejoiners). At follow-up, 384/480 (80%) were re-evaluated, including 76/92 (83%) rejoiners. In T1, participants who participated once and those who later rejoined T2 exhibited similar responses to their first intervention, including comparable weight-loss (-3.3% vs. -3.4%; FDR = 0.93). However, T1 + T2 rejoiners began their second intervention with a similar baseline BMI to their first (31.8 kg/m 2 vs. 31.3 kg/m 2 ; FDR = 0.12). Nevertheless, they presented a more favourable abdominal fat and metabolic profiles at T2 baseline than at their initial T1 baseline (visceral adipose tissue (VAT): 135.5 cm 2 vs. 160.0 cm 2 ; homeostatic model assessment of insulin resistance (HOMA-IR): 3.8 vs. 4.5; high density lipoprotein cholesterol (HDL-C)/Triglycerides: 3.6 vs. 4.2; all FDR < 0.05). In response to T2, rejoiners exhibited attenuated improvements compared to those achieved during their previous T1 intervention (weight: -1.5% vs. -3.5%; VAT: -7.2% vs. -33.3%; deep subcutaneous adipose tissue (SAT): -4.0% vs. -31.9%; superficial SAT: -3.3% vs. -25.4%; all FDR < 0.05), and compared to first-time T2 participants (weight: -3.5%; FDR < 0.05, VAT: -11.6%; FDR = 0.20, deep SAT: -9.9%; FDR < 0.05, superficial SAT: -9.3%; FDR = 0.05). Yet, 5 years after completing T2, T1 + T2 rejoiners exhibited significantly less weight regain compared with first-time T2 participants (+ 0.2% vs. + 2.9%; FDR < 0.05), deep-SAT regain (+ 2.4% vs. + 13.3%; FDR < 0.05), and superficial-SAT regain (+ 12.8% vs. + 24.3%; FDR < 0.05), though similar VAT regain. Overall, although T1 + T2 rejoiners had higher baseline obesity parameters than first-time participants, they presented comparable values by the 5- and 10-year follow-up. Despite an attenuated weight-loss response, repeated engagement in a structured lifestyle intervention yields meaningful long-term impacts with sustainable metabolic benefits. CENTRAL (Clinical-trials-identifier:NCT01530724); DIRECT-PLUS (Clinical-trials-identifier:NCT03020186).