Alogliptin

Limits on what this shows

• Key negative/null findings: No study located showed alogliptin impairing mitochondrial structure or function in any model.
• At-risk subgroups: Not applicable; this is a protective, not a depletion, signal, and applies only to diabetic-stress animal models studied.
• Counter-evidence on record: No human data locate this effect in people; animal models used pre-existing diabetic cardiac stress, so the finding may not generalize outside that context. No independent replication by a group other than Zhang X's own lab was found.

Regulatory status

Not addressed in the FDA label; no mitochondrial toxicity signal or warning.

Population evidence

Zhang X et al., 2017 (PMID 28507060): diabetic rabbit model, alogliptin alleviated atrial remodeling and improved mitochondrial function and biogenesis markers. Zhang X et al., 2018 (PMID 30591063): diabetic rabbits, alogliptin prevented diastolic dysfunction and preserved left ventricular mitochondrial function. Zhu B et al., 2019 (PMID 30644630): high-fat-diet mice, alogliptin improved survival and metabolic health. All animal studies; no human replication found.

Mechanism

Proposed AMPK/PGC-1α-linked mitochondrial biogenesis downstream of DPP-4 inhibition and incretin potentiation, named in the Zhang 2017/2018 sources.

Counter-evidence held on record

This is not a depletion signal and must never be marketed as one. It is mechanistic, animal-only evidence of a possible protective effect under diabetic metabolic stress, unconfirmed in humans, and shares its underlying source material with the ATP production entry below (see overlap map).

Limits on what this shows

• Key negative/null findings: None located specific to alogliptin.
• At-risk subgroups: Not applicable; protective direction only.
• Counter-evidence on record: None of these models isolates a direct antioxidant drug action from the effect of improved glycemic control itself; better glucose control independently lowers oxidative-stress markers in diabetic models, so this may be an indirect metabolic effect rather than a specific pharmacologic one. The Kabel 2018 study used alogliptin combined with zinc, confounding attribution to alogliptin alone.

Regulatory status

Not addressed in the FDA label.

Population evidence

Jiao LJ et al., 2026 (PMID 41428503): diabetic cardiomyopathy mice and cardiomyocytes, alogliptin reduced oxidative stress via AURKB/NLGN2 signaling. Fahmy MM et al., 2025 (PMID 41096869): rat model, alogliptin mitigated methotrexate-induced nephrotoxicity. Kabel AM et al., 2018 (PMID 29091894): Wistar rats, zinc/alogliptin combination attenuated doxorubicin-induced testicular toxicity (combination therapy, not alogliptin alone). Yisireyili M et al., 2016 (PMID 27509090): murine model, alogliptin improved stress-induced insulin resistance. All animal or in vitro; none human; none used alogliptin alone in a euglycemic/uninjured control context.

Mechanism

Proposed antioxidant/anti-inflammatory downstream effect of DPP-4 inhibition and incretin signaling; not fully characterized at the biochemical level in these sources.

Counter-evidence held on record

Mechanism-only, animal/in vitro evidence, confounded by glycemic improvement and (in one source) co-administered zinc. Never a basis for antioxidant-supplementation marketing claims.

Limits on what this shows

• Why no grade: A direct PubMed search ("alogliptin copper") returned an explicit zero-result count ("No results were found," result count 0). No class-level DPP-4-inhibitor/copper literature was located in the searches conducted. No circulating consumer claim of an alogliptin-copper interaction was identified. Both dual conditions for ungraded (Step 7) are met on the channels actually reachable this session; see the access note below for a disclosed tooling limitation affecting cross-checks against Europe PMC, Crossref, and Semantic Scholar.

Limits on what this shows

• Why no grade: PubMed was searched with three phrasings ("alogliptin iron," "alogliptin iron deficiency," "alogliptin iron status"). The first two attempts returned a bot-verification page rather than results; the third returned an explicit zero-result count. No class-level DPP-4-inhibitor/iron literature was located. No circulating consumer claim was identified. Europe PMC and the Crossref and Semantic Scholar APIs could not be reached this session (repeated 429/blocked responses) to cross-check further. This is a genuine evidence gap on the channels reachable this session, disclosed rather than forced into another tier.

Limits on what this shows

• Key negative/null findings: None located for this class relationship; note the Ryan 2020 study is an active-comparator design (DPP-4 inhibitor vs. metformin), which does not test either drug against no treatment.
• At-risk subgroups: Not applicable; mechanistic/class-level only.
• Counter-evidence on record: No alogliptin-specific human or animal microbiome data exist. The direction reported for the generic DPP-4-inhibitor arm (increased butyrate producers) may be beneficial rather than harmful, which undermines a straightforward "risk" framing even at the class level.

Regulatory status

Not addressed in the FDA label.

Population evidence

Olivares M et al., 2018 (PMID 29797022): mice, the DPP-4 inhibitor vildagliptin (not alogliptin) altered gut microbiota composition. Ryan PM et al., 2020 (PMID 31445961), Canadian Journal of Diabetes: obese mice, an unnamed/generic DPP-4 inhibitor (drug identity not confirmed as alogliptin in the sections retrieved) differentially modulated intestinal microbiota versus metformin, increasing butyrate-producing organisms. Neither study used alogliptin; both are class-level (Tier C) for this drug.

Mechanism

Proposed via incretin (GLP-1/GIP) potentiation affecting gut motility and short-chain-fatty-acid-producing bacteria; plausible for alogliptin given the shared class mechanism, but unconfirmed for this specific molecule.

Counter-evidence held on record

Class extrapolation from vildagliptin and an unnamed DPP-4 inhibitor; do not present as an established or even a specifically direction-confirmed alogliptin effect.

Limits on what this shows

• Key negative/null findings: None located.
• At-risk subgroups: Not applicable.
• Counter-evidence on record: No study measured ATP output, ATP/ADP ratio, or cellular oxygen consumption rate directly; biogenesis markers are a proxy, not a direct measurement of ATP production, so this entry is weaker than the mitochondrial-structure finding it is drawn from.

Regulatory status

Not addressed in the FDA label.

Population evidence

Zhang X et al., 2017 (PMID 28507060) and Zhang X et al., 2018 (PMID 30591063): diabetic rabbits, mitochondrial biogenesis and function markers. Same sources as the mitochondrial-burden entry above (see overlap map).

Mechanism

AMPK/PGC-1α-mediated mitochondrial biogenesis proposed as the route to improved ATP-generating capacity; not directly assayed.

Counter-evidence held on record

This entry rests on the same underlying sources as mitochondrial burden above; do not count the two as independent confirmations of the same finding (see overlap map).

Limits on what this shows

• Why no grade: A direct PubMed search ("alogliptin hemoglobin anemia") returned an explicit zero-result count. No hematologic safety signal was reported in the EXAMINE cardiovascular-outcomes trial materials located (White WB et al., 2011 protocol, PMID 21982652; n=5,380 patients with type 2 diabetes and recent acute coronary syndrome) or its secondary analyses reviewed. No circulating consumer claim was identified. Both dual conditions for ungraded are met on the channels reachable this session.