Greater hepatic lipid saturation is associated with impaired glycaemic regulation in men with metabolic dysfunction-associated steatotic liver disease but is not altered by 6 weeks of exercise training.

AIMS: To examine the impact of impaired glycaemic regulation (IGR) and exercise training on hepatic lipid composition in men with metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: In Part A (cross-sectional design), 40 men with MASLD (liver proton density fat fraction [PDFF] ≥5.56%) were recruited to one of two groups: (1) normal glycaemic regulation (NGR) group (glycated haemoglobin [HbA1c] < 42 mmol∙mol-1 [<6.0%]; n = 14) or (2) IGR group (HbA1c ≥ 42 mmol∙mol-1 [≥6.0%]; n = 26). In Part B (randomized controlled trial design), participants in the IGR group were randomized to one of two 6-week interventions: (1) exercise training (EX; 70%-75% maximum heart rate; four sessions/week; n = 13) or (2) non-exercise control (CON; n = 13). Saturated (SI; primary outcome), unsaturated (UI) and polyunsaturated (PUI) hepatic lipid indices were determined using proton magnetic resonance spectroscopy. Additional secondary outcomes included liver PDFF, HbA1c, fasting plasma glucose (FPG), homeostatic model assessment of insulin resistance (HOMA-IR), peak oxygen uptake (VO2 peak), and plasma cytokeratin-18 (CK18) M65, among others. RESULTS: In Part A, hepatic SI was higher and hepatic UI was lower in the IGR versus the NGR group (p = 0.038), and this hepatic lipid profile was associated with higher HbA1c levels, FPG levels, HOMA-IR and plasma CK18 M65 levels (rs ≥0.320). In Part B, hepatic lipid composition and liver PDFF were unchanged after EX versus CON (p ≥ 0.257), while FPG was reduced and VO2 peak was increased (p ≤ 0.030). ΔVO2 peak was inversely associated with Δhepatic SI (r = -0.433) and positively associated with Δhepatic UI and Δhepatic PUI (r ≥ 0.433). CONCLUSIONS: Impaired glycaemic regulation in MASLD is characterized by greater hepatic lipid saturation; however, this composition is not altered by 6 weeks of moderate-intensity exercise training.

Effectiveness of integrating a pragmatic pathway for prescribing liraglutide 3.0 mg in weight management services (STRIVE study): a multicentre, open-label, parallel-group, randomized controlled trial.

Background: An effective prescribing pathway for liraglutide 3 mg, an approved obesity pharmacotherapy, may improve treatment access. This trial compared a targeted prescribing pathway for liraglutide 3 mg with multiple stopping rules in specialist weight management services (SWMS) to standard SWMS care. Methods: This phase four, two-year, multicentre, open-label, parallel-group, real-world randomized clinical trial (ClinicalTrials.gov: NCT03036800) enrolled adults with BMI ≥35 kg/m2 plus prediabetes, type 2 diabetes, hypertension or sleep apnoea from five SWMS in Ireland and UK. Participants were randomly allocated (2:1, stratified by centre and BMI) to SWMS care plus a targeted prescribing pathway for once daily subcutaneous liraglutide 3 mg (intervention) with stopping rules at 16 (≥5% weight loss, WL), 32 (≥10% WL) and 52 weeks (≥15% WL) or to SWMS care alone (control) through an online randomization service. The primary outcome was WL ≥15% at 52 weeks, assessed by complete cases analysis. All randomized participants were included in safety analysis. Findings: From November 28, 2017 to February 28, 2020, 434 participants were screened, and 392 randomized (260 intervention; 132 control), while 294 (201 intervention; 93 control) included in the 52 weeks complete case analysis. More intervention than control participants achieved WL ≥15% at 52 weeks [51/201 (25.4%) vs 6/93 (6.5%); odds ratio 5.18; 95% CI 2.09, 12.88; p < 0.0001]. More adverse events occurred in the intervention (238/260, 91.5%; two deaths) than control (89/132, 67.4%; no deaths) group. Interpretation: A targeted prescribing pathway for liraglutide 3 mg helps more people achieve ≥15% WL at 52 weeks than standard care alone. Funding: Novo Nordisk A/S.