Estimating the subgroup and testing for treatment effect in a post-hoc analysis of a clinical trial with a biomarker

Background Beyond antihyperglycemic effects, metformin may improve cardiovascular outcomes. Patients with type 2 diabetes often have an elevated plasma level of N-terminal pro B-type as a marker of (sub) clinical cardiovascular disease. We studied whether metformin was associated with a reduction in the serum level of N-terminal pro B-type natriuretic peptide (NT-proBNP) in these patients. Methods In the HOME trial 390 insulin-treated patients with type 2 diabetes were randomized to 850 mg metformin or placebo three times daily. Plasma samples were drawn at baseline, 4, 17, 30, 43 and 52 months. In a post-hoc analysis we analyzed the change in NT-proBNP in both groups. We used a longitudinal mixed model analysis adjusting for age, sex and prior cardiovascular disease. In a secondary analysis we assessed a possible immediate treatment effect post baseline. Results Metformin did not affect NT-proBNP levels over time in the primary analysis (-1% [95%CI -4;3, p = 0.62]). In the secondary analysis there was also no sustained time independent immediate treatment effect (initial increase of 17% [95%CI 4;30, p = 0.006] followed by yearly decrease of -4% [95%CI -7;0, p = 0.07]). Conclusions Metformin as compared to placebo did not affect NT-proBNP plasma levels in this 4.3-year placebo-controlled trial. Potential cardioprotective effects of metformin cannot be explained by changes in cardiac pressures or volumes to the extent reflected by NT-proBNP.

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Effects of Low-Volume, High-Intensity Interval Training Compared with Continuous Training on Regional and Global Body Composition in Adults with Metabolic Syndrome: A post hoc Analysis of a Randomized Clinical Trial

Annals of Nutrition and Metabolism ◽

10.1159/000518909 ◽

2021 ◽

pp. 1-10

Author(s):

Juan Carlos Aristizabal ◽

Esperanza Montoya ◽

Yeliana L. Sánchez ◽

Manuela Yepes-Calderón ◽

Raul Narvaez-Sanchez ◽

...

Keyword(s):

Metabolic Syndrome ◽

Clinical Trial ◽

Body Composition ◽

Interval Training ◽

High Intensity Interval Training ◽

Continuous Training ◽

Post Hoc Analysis ◽

Low Volume ◽

High Intensity Interval ◽

Post Hoc

Objective: The aim of this study was to compare the effects of low-volume, high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) on body composition in adults with metabolic syndrome (MS). Methods: This is a post hoc analysis of the randomized clinical trial Intraining-MET. Sixty adults (40–60 years old) were randomized to an MICT (n = 31) or HIIT (n = 29) supervised programme 3 days/week for 12 weeks. MICT sessions were conducted for 36 min at 60% of peak oxygen consumption (VO2peak). HIIT sessions included 6 intervals at 90% VO2peak for 1 min, followed by 2 min at 50% VO2peak. Body composition was assessed with dual energy X-ray absorptiometry. Results: Body weight did not change from pre- to post-training in either MICT (78.9 ± 15.6 kg; 77.7 ± 16.5 kg, p = 0.280) or HIIT groups (76.3 ± 13.4 kg; 76.3 ± 13.7 kg, p = 0.964). Body fat percentage and fat mass (FM) decreased post-training in the MICT (−0.9%; 95% confidence interval [CI]: −0.27 to −1.47 and −0.7 kg; 95% CI: −0.12 to −1.30) and HIIT groups (−1.0%; 95% CI: −0.32 to −1.68 and −0.8 kg; 95% CI: −0.17 to −1.47). Compared to the HIIT programme, MICT significantly reduced android FM (−0.14 kg; 95% CI: −0.02 to −0.26). Lean mass (LM) increased post-training in MICT (+0.7 kg; 95% CI: 0.01–1.41) and HIIT groups (+0.9 kg; 95% CI: 0.12–1.64), but only HIIT increased the trunk LM (+0.6 kg; 95% CI: 0.06–1.20). Conclusions: Both MICT and HIIT reduced FM without changing body weight in adults with MS. MICT had additional benefits by reducing the android FM, whereas HIIT seemed to increase LM. Given the characteristics of the post hoc analysis, further research is required to confirm these results.

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