Effects of exercise and exercise timing on energy intake and appetite control: a randomised crossover trial in people with overweight or obesity with and without type 2 diabetes

Background: This randomised crossover trial (ClinicalTrials.gov: NCT05768958) examined how high-intensity interval exercise (HIIE) vs. rest and time of day affect ad libitum energy intake, subjective appetite, and metabolic markers, and whether responses differ by type 2 diabetes (T2D) status. Methods: Fifty-eight adults with overweight/obesity (with and without T2D) completed four laboratory visits (HIIE or rest in the morning or late afternoon). Participants were randomised using a balanced incomplete block design; blinding was not feasible. The primary outcome was ad libitum energy intake; secondary outcomes included 24-h post-visit energy intake, subjective appetite, satiety quotient and metabolic markers (including glucose, insulin, ghrelin, Glucagon-Like Peptide-1, Fibroblast Growth Factor 21 (FGF21), and Growth Differentiation Factor 15 (GDF15)). Findings: Energy intake was lower after HIIE than rest (−361 kJ (95% CI: −520: −202), p < 0.001) with no compensation over the next 24 h. Appetite ratings were lower after HIIE, accompanied by reduced ghrelin and increased FGF21 and GDF15. Time of day did not affect outcomes; however, only participants without T2D consumed less after morning than late afternoon HIIE. FGF21 and GDF15 increased after exercise compared to rest independent of time of day. GDF15 showed a significantly greater response and higher concentrations in participants with T2D. In participants with T2D, morning HIIE elicited higher FGF21 concentrations than late afternoon HIIE. Other time-of-day effects were minimal. No serious adverse events occurred. Interpretation: In conclusion, acute HIIE suppresses energy intake and elevates GDF15 and FGF21 in people with overweight/obesity, with modest timing effects that differ by diabetes status. Funding: Novo Nordisk A/S.