This Phase 2a study evaluates whether 12 weeks of treatment with investigational MOTS-c improves insulin sensitivity compared with placebo in adults with prediabetes and overweight/obesity. Participants are randomized 1:1 to MOTS-c or placebo, receive standardized lifestyle counseling, and are followed for safety through Week 16.
Mitochondrial-derived peptides (MDPs) are small peptides encoded by mitochondrial DNA that can act as signaling molecules. MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) has been reported to regulate insulin sensitivity and metabolic homeostasis in preclinical studies, with skeletal muscle identified as a key target tissue and AMPK activation proposed as a downstream mechanism. Based on these findings, this trial is designed to test the hypothesis that MOTS-c can improve insulin sensitivity and cardiometabolic risk markers in humans with early metabolic dysfunction. The study includes a screening period (up to 4 weeks), a 12-week double-blind treatment period, and a 4-week post-treatment safety follow-up. Efficacy is assessed using a 75 g oral glucose tolerance test (OGTT)-derived insulin sensitivity index and standard metabolic endpoints (HbA1c, fasting glucose, lipids, body weight, and waist circumference). Safety assessments include adverse events, vital signs, ECG, and laboratory testing.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
120
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China
RECRUITINGChange from baseline in OGTT-derived insulin sensitivity (Matsuda Index)
Time frame: 12 Weeks
Incidence of treatment-emergent adverse events (TEAEs)
Time frame: 16 weeks
Change from baseline in HbA1c.
Time frame: 12 Weeks
Change from baseline in fasting glucose
Time frame: 12 weeks
Change from baseline in 2-hour plasma glucose during 75 g OGTT.
Time frame: 12 weeks
Immunogenicity (anti-drug antibodies, if applicable).
Time frame: 16 weeks
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Fixed dose once daily for 12 weeks