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Alternate-day alternating monotherapy (q48h) versus daily concomitant atorvastatin–fenofibrate in adults with type 2 diabetes and mixed dyslipidemia: a 12-week randomized non-inferiority trial

Year: 2026

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: To test the non-inferiority of alternate-day alternating monotherapy (q48h) versus daily concomitant atorvastatin–fenofibrate for change in LDL-C in adults with T2DM and mixed dyslipidemia (margin δ = 13 mg/dL). Single-center, randomized, parallel-group non-inferiority trial (12 weeks). Patients (N = 94) were allocated 1:1 to Daily concomitant therapy (atorvastatin 10 mg plus fenofibrate 100 mg once daily) or Alternating monotherapy (q48h), with fixed doses maintained throughout the 12-week study and no dose titration. Primary outcome: ΔLDL-C with 90% CIs versus δ. Analyses were intention-to-treat; Analyses followed intention-to-treat with LOCF; multiplicity for secondary endpoints was controlled (Holm/FDR). Eighty-six completed follow-ups. Both regimens improved TG, total cholesterol, LDL-C, and HDL-C; between-group differences in change were not significant across lipid or metabolic/safety markers. For LDL-C, the 90% CI for (Alternating − Daily) lay entirely within δ, demonstrating non-inferiority. Renal function remained stable; no severe adverse events; ΔAST/ΔALT did not differ between groups. Over 12 weeks, Alternating monotherapy (q48h) was non-inferior to Daily concomitant atorvastatin–fenofibrate for LDL-C lowering, with similar secondary outcomes and acceptable tolerability. Findings support clinical feasibility of a simplified alternate-day schedule; no formal economic analysis was performed. Longer studies with objective adherence assessment are warranted. Iranian Registry of Clinical Trials (IRCT): IRCT20250718066536N1. Registered retrospectively on 18 July 2025. Patient enrolment occurred from August 2024 to June 2025. The protocol and the primary/secondary endpoints were finalized prior to data analysis. Mixed dyslipidemia is a common lipid disorder in type 2 diabetic patients that increases cardiovascular risk. Combination therapy with atorvastatin and fenofibrate is more effective in improving lipid profiles compared to monotherapy. This study evaluated whether administering the combination therapy on alternate days could offer similar efficacy to daily dosing. Both daily and alternate-day regimens significantly improved lipid parameters with no significant difference in efficacy. Alternating monotherapy (q48h) may reduce pill burden with comparable short-term lipid efficacy; adherence was not objectively measured.

Source: BMC Endocrine Disorders

DOI: 10.1186/s12902-025-02156-z

Authors: Soheil Shahramirad, Milad Rezvani, Roya Jahanbazi, Mohammadreza Vataniman, Nasrin Razavianzadeh

Institutions: Islamic Azad University, Shahrood, Shahroud University of Medical Sciences, Islamic Azad University, Yazd, Hormozgan University of Medical Sciences

Language: English

Topic: Lipoproteins and Cardiovascular Health

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,190