THE METMYD STUDY: baseline data and early results on efficacy and safety of metformin in myotonic dystrophy type 1

Erica Frezza

THE METMYD STUDY: baseline data and early results on efficacy and safety of metformin in myotonic dystrophy type 1

Autori

ERICA FREZZA (DEPARTMENT OF SYSTEMS MEDICINE, UNIVERSITY OF ROME “”TOR VERGATA””, VIA MONTPELLIER 1, 00133 ROME, ITALY. – NEUROLOGIA)
SALVATORE ROSSI (INSTITUTE OF NEUROLOGY, DEPARTMENT OF NEUROSCIENCE, CATHOLIC UNIVERSITY OF SACRED HEART, ROME, ITALY – NEUROLOGIA)
ALESSIA PERNA (CENTER FOR NEUROMUSCULAR AND NEUROLOGICAL RARE DISEASES, SAN CAMILLO FORLANINI HOSPITAL, ROME, ITALY – NEUROLOGIA)
ELISABETTA BUCCI (DEPARTMENT OF NEUROSCIENCE, MENTAL HEALTH AND SENSORY ORGANS, S. ANDREA HOSPITAL, UNIVERSITY OF ROME “”LA SAPIENZA””, ROME, ITALY – NEUROLOGIA)
GIULIA GRECO (DEPARTMENT OF SYSTEMS MEDICINE, UNIVERSITY OF ROME “”TOR VERGATA””, VIA MONTPELLIER 1, 00133 ROME, ITALY – NEUROLOGIA)
MARIANGELA GOGLIA (DEPARTMENT OF SYSTEMS MEDICINE, UNIVERSITY OF ROME “”TOR VERGATA””, VIA MONTPELLIER 1, 00133 ROME, ITALY. – NEUROLOGIA)
VITTORIO RISO (INSTITUTE OF NEUROLOGY, DEPARTMENT OF NEUROSCIENCE, CATHOLIC UNIVERSITY OF SACRED HEART, ROME, ITALY – NEUROLOGIA)
VIRGINIA VERONICA VISCONTI (DEPARTMENT OF BIOMEDICINE AND PREVENTION, GENETICS UNIT, UNIVERSITY OF ROME “”TOR VERGATA””, VIA MONTPELLIER 1, 00133 ROME, ITALY – GENETICA)
ANNALISA BOTTA (DEPARTMENT OF BIOMEDICINE AND PREVENTION, GENETICS UNIT, UNIVERSITY OF ROME “”TOR VERGATA””, VIA MONTPELLIER 1, 00133 ROME, ITALY – GENETICA)
MARZIA NUCCETELLI (DEPARTMENT OF LABORATORY MEDICINE, TOR VERGATA UNIVERSITY HOSPITAL, VIALE OXFORD 81, 00133 ROME, ITALY – MEDICINA DI LABORATORIO)
GIOVANNI ANTONINI (UNIT OF NEUROMUSCULAR DISEASES, DEPARTMENT OF NEUROLOGY MENTAL HEALTH AND SENSORY ORGANS (NESMOS), FACULTY OF MEDICINE AND PSYCHOLOGY, ‘SAPIENZA’ UNIVERSITY OF ROME, SANT’ANDREA HOSPITAL, ROME, ITALY – NEUROLOGIA)
ANTONIO PETRUCCI (CENTER FOR NEUROMUSCULAR AND NEUROLOGICAL RARE DISEASES, SAN CAMILLO FORLANINI HOSPITAL, ROME, ITALY – NEUROLOGIA)
GABRIELLA SILVESTRI (INSTITUTE OF NEUROLOGY, DEPARTMENT OF NEUROSCIENCE, CATHOLIC UNIVERSITY OF SACRED HEART, ROME, ITALY – NEUROLOGIA)
ROBERTO MASSA (DEPARTMENT OF SYSTEMS MEDICINE, UNIVERSITY OF ROME “”TOR VERGATA””, VIA MONTPELLIER 1, 00133 ROME, ITALY – NEUROLOGIA)

Presentatore

ERICA FREZZA (DEPARTMENT OF SYSTEMS MEDICINE, UNIVERSITY OF ROME “TOR VERGATA”, VIA MONTPELLIER 1, 00133 ROME, ITALY)

Modalità

Oral Communication

Abstract

“DM1 is still orphan of a cure or disease-modifying treatment. While gene therapy and antisense-oligonucleotide treatments are under investigation, recent studies showed that metformin can modify the aberrant alternative splicing causative of DM1.
The aim of this study is to evaluate the superiority of a 24 month-treatment with the biguanide drug metformin over placebo on motility and strength parameters in adult DM1 patients.
METMYD is a multi-center, randomized, triple-blind, two-arm, phase III, clinical trial. The primary endpoint is a better performance at the 6MWT at the end of study as compared to baseline. Secondary clinical endpoints explore muscle quantitative testing of upper and lower limbs, dexterity, fatigue. In addition, quantitation of circulating alternative splicing products deficient in DM1 and of markers of oxidative stress is performed before and after treatment.
Enrollment started in January 2020 and the study ended in December 2023. One-hundred and forty-nine patients were enrolled and 146 were randomized either to metformin or placebo. The two arms at baseline did not differ for sex, age, BMI, HOMA index and 6MWT. Fifty-four (37%) patients (29 on metformin, 25 on placebo) dropped out for various reasons, mainly non-compliance, consent withdrawal and diarrhea and 92 patients completed the protocol.
The METMYD study shows that a long-term pharmacological intervention is feasible in DM1 patients, even during the COVID-19 pandemics. Metformin showed to be safe when administered in non-diabetic DM1 patients, the only common AE being diarrhea, as in general population. The analysis of clinical and laboratory measures is underway.”