Endocrinology · Medical Literature
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.
Abstract
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. 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)). 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. 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. Novo Nordisk A/S.
Clinical relevance
Does a single bout of high-intensity interval exercise (HIIE) versus rest, and the time of day at which it is performed (morning vs. late afternoon), differentially affect ad libitum energy intake, subjective appetite, and circulating metabolic markers in adults with overweight or obesity, with and without type 2 diabetes? __SNAPSHOT__ {"studyDesign":"Randomised crossover trial (balanced incomplete block design); ClinicalTrials.gov NCT05768958","setting":"Copenhagen University Hospital – Steno Diabetes Center Copenhagen, Denmark; conducted March 2023 to August 2024","sampleSize":"n = 58 adults with overweight/obesity (with and without T2D); each participant completed four laboratory visits","population":"Adults with overweight or obesity (BMI criteria not explicitly reported in abstract), with and without established type 2 diabetes (T2D); exact age range, sex distribution, HbA1c, and medication details not reported in abstract","intervention":"Acute high-intensity interval exercise (HIIE) performed either in the morning or late afternoon","comparator":"Rest (matched for time of day: morning or late afternoon); 2×2 factorial crossover across four conditions (morning HIIE, afternoon HIIE, morning rest, afternoon rest)","primaryOutcome":"Ad libitum energy intake at a meal offered 15 minutes after the exercise or rest condition","followUp":"24 hours post-visit for secondary energy intake and appetite assessment","fundingSource":"Partial industry affiliation noted (co-authors affiliated with Novo Nordisk A/S); additional funding sources not reported in abstract"}
Key findings
Primary outcome: Ad libitum energy intake was significantly lower after HIIE compared with rest by −361 kJ (95% CI: −520 to −202; p < 0.001). Whether this reduction is clinically meaningful beyond a single meal context is not established. No compensatory increase in energy intake was observed over the subsequent 24 hours. Subjective appetite ratings were lower after HIIE, accompanied by suppressed circulating ghrelin and elevated FGF21 and GDF15 concentrations. NNT is not calculable from the reported data. Regarding time of day: overall, time of day did not significantly affect energy intake or appetite outcomes; however, a subgroup interaction was identified in which only participants without T2D consumed less energy after morning HIIE compared with late afternoon HIIE. In participants with T2D, morning HIIE elicited higher FGF21 concentrations than late afternoon HIIE; GDF15 showed a significantly greater absolute response in participants with T2D than in those without. Diurnal variation in the GDF15 response was also observed, with higher concentrations after late afternoon exercise than morning exercise overall. Absolute effect sizes for all secondary outcomes (including satiety quotient, GLP-1, insulin, and glucose) are not reported in the abstract. No serious adverse events are described in the abstract.
Practice implications
This trial establishes that a single bout of HIIE acutely reduces ad libitum energy intake (by approximately 361 kJ) and suppresses appetite-related hormones — including ghrelin — while elevating anorexigenic signals FGF21 and GDF15, without apparent 24-hour compensatory hyperphagia in adults with overweight or obesity. These findings apply to adults with and without T2D, as energy intake and metabolic marker responses were broadly similar across both subgroups. The time-of-day effect on energy intake was modest and present only in the non-T2D subgroup (morning > afternoon suppression), which may reflect blunted or absent circadian variation in appetite physiology among individuals with T2D — a biologically plausible but hypothesis-generating observation that requires prospective confirmation. Patients who were excluded or not adequately represented include those on GLP-1 receptor agonists or other medications known to affect appetite, those with severe obesity, older adults with functional limitations precluding HIIE, and individuals with type 1 diabetes. The clinical importance of a single-session ~361 kJ intake reduction is uncertain without data on whether repeated HIIE produces sustained reductions in total daily energy balance. Findings from a single-meal, controlled laboratory setting may not translate to free-living conditions where food availability, palatability, and social context vary. The role of FGF21 and GDF15 as mechanistic mediators versus epiphenomena cannot be determined from this design. IMPORTANT LIMITATION: This summary is based solely on the published abstract; full methods, subgroup definitions, statistical models for secondary outcomes, and potential confounders are not visible and should be reviewed in the complete manuscript before clinical application. __LIMITATIONS__ Blinding was not feasible given the nature of the intervention, introducing potential performance and detection bias in subjective appetite ratings.,Balanced incomplete block crossover design — not all participants completed all four conditions — may introduce selection and carryover bias if not adequately accounted for.,Single-session, acute design in a controlled laboratory setting; generalisability to free-living, habitual exercise contexts is limited.,Subgroup analyses by T2D status appear post-hoc or were secondary; the trial may not have been adequately powered for these comparisons.,The meal offered 15 minutes post-exercise was standardised and laboratory-controlled; palatability and food choice may have differed from free-living conditions, potentially exaggerating appetite suppression.,Partial industry co-authorship (Novo Nordisk A/S employees listed as co-authors) introduces potential for conflict of interest, particularly relevant given commercial interest in FGF21 and GDF15 as therapeutic targets.,Absolute effect sizes, confidence intervals, and p-values for all secondary outcomes (appetite scales, satiety quotient, GLP-1, glucose, insulin) are not reported in the abstract, precluding full evaluation.,Long-term effects on weight, body composition, and sustained energy balance cannot be inferred from a single acute crossover.,Demographic details including age range, sex distribution, HbA1c, and concurrent diabetes medications are not reported in the abstract, limiting assessment of generalisability.,Statistical significance of the primary outcome is clear (p < 0.001), but clinical significance of a ~361 kJ reduction in a single controlled meal on overall energy balance over weeks to months is not established. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ A single bout of HIIE significantly reduced ad libitum energy intake by ~361 kJ compared with rest in adults with overweight or obesity, with or without T2D, with no 24-hour compensatory eating — a finding supported by concurrent suppression of ghrelin and elevation of FGF21 and GDF15. The time of day of exercise had minimal overall impact on energy intake or appetite, with a modest morning-favoring effect observed only in the non-T2D subgroup. These results are hypothesis-generating regarding exercise timing and metabolic phenotype but are based on a single acute laboratory session; they should inform counseling about exercise-appetite interactions rather than prompt changes to structured diabetes or obesity management protocols without further confirmatory evidence.