Focusing more on Mitoglitazone, from this thread: New ITP result: Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female mice
The human clinical data on this drug:
Here’s everything publicly available (to my knowledge) on mitoglitazone (MSDC-0160) in humans—organized by indication and trial phase, with design, dose, outcomes, and safety.
Trials in people
Type 2 diabetes (T2D)
Phase IIb, randomized, double-blind, multicenter, 12 weeks (n=258)
Arms: mitoglitazone 50, 100, or 150 mg QD; pioglitazone 45 mg QD (active comparator); placebo.
Primary/Key outcomes: fasting glucose, HbA1c, safety markers (hematocrit/hemoglobin as fluid-retention proxy), adiponectin, body weight/waist, lipoprotein particle size.
Findings:
- The two active drugs (MSDC-0160 and pioglitazone) lowered fasting glucose to a similar extent.
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HbA1c reductions with MSDC-0160 (100 & 150 mg) were not different from pioglitazone at 12 weeks.
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Less fluid retention with MSDC-0160 (≈50% less reduction in hematocrit/hemoglobin vs pioglitazone).
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Smaller rise in HMW adiponectin than pioglitazone (interpreted by authors as less adipose expansion).
- Weight/waist changes trended smaller with MSDC-0160 vs pioglitazone over 12 weeks.
Safety/tolerability: acceptable over 12 weeks; edema/volume-expansion signals were lower than with pioglitazone. (考研)
Notes: The publication includes PK run-in in healthy volunteers (once-daily for 7 days) used for dose selection; exposures at 50–150 mg are shown and supported the Phase IIb dosing. (考研)
Alzheimer’s disease (AD), non-diabetic participants
Phase IIa-style exploratory RCT, 12 weeks (MSDC-0160 150 mg QD)
Design: randomized, double-blind, placebo-controlled; n=29 (MSDC-0160 = 16; placebo = 13).
Primary readouts: FDG-PET brain glucose metabolism in predefined AD-vulnerable regions; cognitive/safety secondary.
Findings:
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No significant between-arm difference in predefined regions when referenced to pons or whole brain.
- With cerebellum as reference, MSDC-0160 maintained glucose metabolism over 12 weeks, while placebo declined in anterior/posterior cingulate, parietal, lateral temporal, and medial temporal cortices (exploratory).
- Voxel-based analyses suggested additional FDG-PET differences consistent with central effects.
Safety: generally well tolerated over 12 weeks. (PMC)
Registered trial record (same study): 3-month MSDC-0160 150 mg vs placebo with FDG-PET and cognition. (ClinicalTrials)
Other human-facing records
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T2D Phase IIb registration (matching the 12-week RCT above) appears on trial registries/aggregators under NCT01103414, describing “Safety, Tolerability and Efficacy of Three Dose Levels of Mitoglitazone (MSDC-0160).” (ClinicalTrials)
- Company and foundation pages summarize the above AD study and state that MSDC-0160 completed PoC in T2D and was advanced for neurodegenerative indications. (Good for context; not primary data.) (Metabolic Solutions Development Company)
What these human data say (bottom line)
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Glucose-lowering efficacy: In T2D, mitoglitazone produced HbA1c and fasting glucose improvements comparable to pioglitazone over 12 weeks, with less fluid-retention signal—consistent with its design as a “PPAR-sparing” insulin sensitizer that modulates the mitochondrial pyruvate carrier (MPC/mTOT) rather than PPAR-γ. (考研)
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Neurodegeneration signal: In mild AD (non-diabetic), an exploratory 12-week RCT showed FDG-PET preservation in some analyses (cerebellar reference; voxelwise) but no confirmatory primary-region difference using pons/whole-brain references. Safety was acceptable over 3 months. Larger, longer trials would be needed to judge clinical benefit. (PMC)
Mechanism notes relevant to translation
Structural/biophysical work since 2024–2025 confirmed that mitoglitazone directly binds and inhibits the human MPC complex, aligning with the clinical “PPAR-sparing insulin sensitizer” profile observed in the T2D RCT. (This is mechanistic context rather than clinical data.) (Science)
