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MyDeficiencies

Mecasermin

Somatropin agonist / rhIGF-1 replacement

Also sold as Increlex.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Mecasermin has no classical drug-nutrient depletion mechanism. It is a subcutaneously injected peptide hormone, not an orally absorbed small molecule, so it bypasses gastric-pH, chelation, and gut-transit mechanisms entirely. Its own label states it is metabolized by ordinary peptide catabolism in liver and kidney, not by cytochrome P450 enzymes, and it induces no hepatic enzymes. The drug's dominant, well-documented safety signal is not a nutrient deficiency at all: it is the drug's own intended insulin-mimetic pharmacology. Hypoglycemia was reported in 42% of subjects across the pivotal clinical trial program, was most frequent in the first month of treatment and in younger children, and included seizures and loss of consciousness in some cases. Per this protocol's Hard Rule 2, that effect is filed here as the drug's own designed pharmacologic action, not graded as a nutrient-style entry, and it is covered in the pharmacokinetic basis, the monitoring panel, and the safety review below rather than in the graded-entries table.

Somatropin agonist / rhIGF-1 replacement · ATC H01AC03 · also sold as Increlex · reviewed 2026-09-26. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Mecasermin in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
severe: two or more independent Tier A sources, this drug in the studied cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
moderate: at least one Tier A source with this drug in the cohort showing a real effect, but bounded by exposure window, population, or a functional (not circulating) deficit; the boundary is stated in the entry title.
Yellow — Low
low/theoretical: mechanistic plausibility only (Tier B), or class/species extrapolation (Tier C) where at least one related study exists but this drug or this species was not directly studied; also used for context flags and reverse-direction (protective or retention) findings.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: no Tier B/C evidence exists to support even a yellow grade, and no circulating consumer claim exists to rebut as white. A genuine gap in the literature or in what could be accessed during this review, not a finding of safety.

What the research found

Sodium / fluid retention, bounded to short-term healthy-adult dosing

Orange — Moderate

See study details

Recombinant human IGF-1, the same active molecule as mecasermin, measurably retains sodium and expands extracellular fluid volume in healthy adults over six days; this is a retention risk, not a deficiency, and has not been directly re-measured in the labeled pediatric severe-primary-IGFD population on chronic therapy.

Full detail and limits

What the grade means here: moderate: at least one Tier A source with this drug in the cohort showing a real effect, but bounded by exposure window, population, or a functional (not circulating) deficit; the boundary is stated in the entry title. orange

Limits on what this shows

  • Key negative/null findings: Plasma aldosterone did not change and plasma volume itself was unchanged, arguing against a simple volume-expansion-via-aldosterone explanation; the renin increase did not reach statistical significance [3].
  • At-risk subgroups: Patients with pre-existing cardiac, hepatic, or renal disease where additional fluid retention carries clinical weight; young children in the first months of therapy, where dose titration is most active.
  • Counter-evidence on record: This is a healthy-adult, 6-day, non-mecasermin-branded exposure; it has not been replicated as a direct serum-sodium or edema-incidence outcome in children with severe primary IGFD on long-term Increlex therapy, so the magnitude and persistence of the effect under labeled dosing and population is not established at Tier A strength for that population.

Regulatory status

Not a named warning in the Increlex label as an electrolyte abnormality; the label separately documents edema-adjacent injection-site and lipohypertrophy effects but does not quantify serum sodium changes [1].

Population evidence

Randomized, placebo-controlled crossover study, 8 healthy male subjects aged 23 to 30, recombinant human IGF-1 50 µg/kg three times daily for 6 days versus placebo for 6 days. Extracellular fluid volume expanded while plasma volume stayed unchanged; daily sodium excretion fell; N-terminal proANF (atrial natriuretic factor) was suppressed during IGF-1 administration; plasma renin rose non-significantly; aldosterone was unaffected [3].

Mechanism

Named: suppression of atrial natriuretic factor together with a mild renin-activity increase, producing renal sodium and fluid retention, the same axis proposed to mediate growth hormone's fluid-retaining effect [3].

Counter-evidence held on record

This is a retention/excess-direction finding, not a deficiency. Supplemental dietary sodium is not indicated and would compound the risk rather than correct it; the practical action is monitoring for edema and weight gain, particularly during dose titration, not sodium repletion.

Phosphate, mechanistic retention signal

Yellow — Low

See study details

In vitro and rodent data on insulin and IGF-1 point toward increased renal phosphate reabsorption and stimulated cellular phosphate uptake, mirroring the well-characterized GH/IGF-1/PTH bone axis; this has not been measured as a serum-phosphate outcome in mecasermin-treated patients.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class/species extrapolation (Tier C) where at least one related study exists but this drug or this species was not directly studied; also used for context flags and reverse-direction (protective or retention) findings. yellow

Limits on what this shows

  • Key negative/null findings: None identified specific to mecasermin; no drug-specific serum phosphate trial was located during this review.
  • At-risk subgroups: Patients with pre-existing hyperphosphatemia or impaired renal phosphate excretion; theoretical only, since no mecasermin-specific case data were found.
  • Counter-evidence on record: No mecasermin-specific human phosphate data, positive or negative, were located; this entry rests entirely on class-level, non-drug-specific mechanistic literature and must not be read as an established clinical finding for this drug.

Regulatory status

Not addressed in the Increlex label [1].

Population evidence

In vitro human osteosarcoma (MG-63) cell studies found insulin and IGF-1 stimulated cellular phosphate uptake [7]; cultured kidney cell studies found IGF-1, together with phosphate deprivation, directly stimulated renal 1,25(OH)2 vitamin D3 synthesis [8]; a narrative review frames GH/IGF-1 signaling as a driver of renal tubular phosphate reabsorption via the PTH axis [9]. None of these studied mecasermin or a severe-primary-IGFD cohort directly; all are Tier C for this drug, disclosed here as bibliographic/title-level citations rather than fully opened full texts for [7], [8], and [9].

Mechanism

Named at the class level: IGF-1 receptor signaling increases cellular and renal tubular phosphate handling and stimulates active vitamin D synthesis, the same axis that supports anabolic bone mineralization during GH/IGF-1 therapy.

Counter-evidence held on record

If real, this is a retention-direction signal, not a deficiency. Phosphate supplementation is not supported by any evidence reviewed here and would run counter to the theoretical direction of this finding.

Calcium, theoretical increased utilization during anabolic growth

Yellow — Low

See study details

Bone-formation marker studies of rhIGF-1 and GH therapy show rising bone-specific alkaline phosphatase, consistent with increased bone turnover and mineral demand during therapy, not with a measured calcium deficit.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class/species extrapolation (Tier C) where at least one related study exists but this drug or this species was not directly studied; also used for context flags and reverse-direction (protective or retention) findings. yellow

Limits on what this shows

  • Key negative/null findings: None identified; no study reviewed measured serum or ionized calcium directly in mecasermin-treated patients.
  • At-risk subgroups: Children in rapid catch-up growth phases, where anabolic demand is highest; those with low dietary calcium or vitamin D intake independent of therapy.
  • Counter-evidence on record: A rising bone-formation marker indicates increased bone-building activity, not a measured calcium deficiency; per Hard Rule 3, an unfalsifiable "tissue calcium is depleted while blood levels stay normal" framing is explicitly rejected here in favor of the bone marker data actually reported.

Regulatory status

Not addressed in the Increlex label [1].

Population evidence

In GH-deficient adults, short-term IGF-1 and GH treatment both raised bone alkaline phosphatase, a bone-formation marker [10]; a separate study found different bone alkaline phosphatase isoform responses to recombinant IGF-1 versus GH therapy [11]. Both are Tier C for mecasermin (GH-deficient adults, not primary IGFD; title-level citation only, full text not opened during this review).

Mechanism

Named at the class level: IGF-1-driven osteoblast activity and skeletal growth increase the calcium and phosphate demand of active bone mineralization, an increased-utilization mechanism (Step 2, category I) rather than an absorption or renal-wasting mechanism.

Counter-evidence held on record

This supports ensuring adequate dietary calcium and vitamin D intake to match growth demand, not a specific supplemental dose; no dose is recommended here, and any calcium/vitamin D adequacy discussion belongs with the prescribing clinician monitoring growth velocity.

Potassium, theoretical insulin-like intracellular shift

Yellow — Low

See study details

IGF-1 receptor signaling activates the same Na+,K+-ATPase-stimulating pathway insulin uses in a non-mammalian model; no human or mammalian data measuring serum potassium during mecasermin therapy were located.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class/species extrapolation (Tier C) where at least one related study exists but this drug or this species was not directly studied; also used for context flags and reverse-direction (protective or retention) findings. yellow

Limits on what this shows

  • Key negative/null findings: None identified; this is a genuine evidence gap at the human level, not a null result.
  • At-risk subgroups: Patients experiencing a severe hypoglycemic episode, where concurrent hypokalemia (by analogy with insulin overdose) would be clinically relevant to check, though this has not been documented for mecasermin specifically.
  • Counter-evidence on record: No mammalian or mecasermin-specific data support or refute this; it is presented strictly as a mechanistic plausibility flag, not a demonstrated clinical effect.

Regulatory status

Not addressed in the Increlex label [1]; no potassium monitoring is specified.

Population evidence

In brown trout, IGF-I increased Na+,K+-ATPase-immunoreactive gill cell density and stimulated Na+,K+-ATPase subunit mRNA [12]. This is a cross-species, non-mammalian, Tier C source, disclosed explicitly because it is the only direct Na+,K+-ATPase evidence located for IGF-1 during this review; it does not establish an effect in humans.

Mechanism

Named but extrapolated: the IGF-1 receptor shares downstream PI3K/Akt signaling with the insulin receptor, and insulin's own well-established pharmacology drives intracellular potassium shift via Na+,K+-ATPase stimulation. The label's own description of mecasermin's "insulin-like hypoglycemic effects" [1] makes this mechanism plausible in principle, but it has not been measured for this drug.

Counter-evidence held on record

No potassium supplementation is recommended on this basis. If used clinically at all, this flag should only inform a prudent lab check during a severe hypoglycemic episode, not a standing supplementation practice.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden, theoretical reversal of a protective deficiency state

Yellow — Low

See study details

Congenital IGF-1 deficiency (Laron syndrome, the exact condition mecasermin treats) is associated in the literature with altered cell-cycle and metabolic-control gene expression that is framed as cancer-protective; restoring IGF-1 signaling is mechanistically plausible to reverse part of that profile, but no study has measured mitochondrial structure or function directly in mecasermin-treated patients.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class/species extrapolation (Tier C) where at least one related study exists but this drug or this species was not directly studied; also used for context flags and reverse-direction (protective or retention) findings. yellow

Limits on what this shows

  • Key negative/null findings: See Fails verification: a specific claim of IGF-1 protecting cardiac mitochondrial/contractile function was traced to a study that has since been formally retracted [16], and is not usable as supporting evidence in either direction.
  • At-risk subgroups: None established; this is a theoretical, population-level consideration for the condition being treated, not a subgroup within treated patients.
  • Counter-evidence on record: No direct mitochondrial-function measurement in mecasermin-treated patients was located; this entry rests on inference from deficiency-state literature about the untreated condition, not on a study of the drug itself.

Regulatory status

Not addressed in the Increlex label [1].

Population evidence

A 2023 review of congenital IGF-1 deficiency (Laron syndrome) describes genome-wide differential expression in cell-cycle, metabolic-control, and apoptosis pathways associated with the deficiency state [14]. This citation is disclosed as title-level and an indexed summary only; the full text was not opened during this review, so the specific mitochondrial claims within it are not independently verified here.

Mechanism

Theoretical only: IGF-1 replacement is mechanistically expected to at least partially reverse the metabolic and apoptotic gene-expression profile associated with the untreated deficiency state, which plausibly touches mitochondrial-adjacent pathways, but no named, drug-specific mitochondrial mechanism was verified.

Counter-evidence held on record

This is a theoretical, mechanistic consideration only, not a demonstrated mitochondrial burden. It does not support any supplement or monitoring recommendation on its own.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress, theoretical reversal of a protective deficiency state

Yellow — Low

See study details

The same Laron syndrome literature that describes IGF-1 deficiency as cancer-protective frames part of that protection through altered metabolic and proliferative signaling; restoring IGF-1 with mecasermin is mechanistically plausible to shift that balance, but no oxidative-stress marker has been directly measured in mecasermin-treated patients.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class/species extrapolation (Tier C) where at least one related study exists but this drug or this species was not directly studied; also used for context flags and reverse-direction (protective or retention) findings. yellow

Limits on what this shows

  • Key negative/null findings: None identified specific to mecasermin.
  • At-risk subgroups: None established.
  • Counter-evidence on record: This is inference from the biology of the untreated deficiency state, not a measured redox marker in treated patients; it should not be overweighted as a "known" oxidative-stress effect of the drug.

Regulatory status

Not addressed in the Increlex label [1].

Population evidence

Same source as the Mitochondrial burden entry above [14]; see Overlap map. Title-level and indexed-summary citation only, full text not opened during this review.

Mechanism

Theoretical: IGF-1/PI3K/Akt signaling is broadly implicated in cellular growth and proliferative signaling, and its chronic absence in Laron syndrome is associated with reduced cancer incidence in the human cohorts described in this literature; whether restoring IGF-1 measurably shifts a systemic oxidative-stress marker in mecasermin-treated patients has not been studied directly.

Counter-evidence held on record

Theoretical only. Does not support an antioxidant supplement recommendation of any kind.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Iron, theoretical increased utilization for erythropoiesis

Yellow — Low

See study details

The same rodent study that showed IGF-1-stimulated erythropoiesis directly measured increased radiolabeled iron incorporation into new erythrocytes, consistent with increased iron utilization for red-cell production rather than iron loss or deficiency.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class/species extrapolation (Tier C) where at least one related study exists but this drug or this species was not directly studied; also used for context flags and reverse-direction (protective or retention) findings. yellow

Limits on what this shows

  • Key negative/null findings: None identified for mecasermin specifically; a dedicated search for mecasermin and copper/iron/ceruloplasmin/hepcidin/ferritin literature returned no drug-specific or class-level source beyond this erythropoiesis study.
  • At-risk subgroups: None established for mecasermin specifically; theoretically, patients with borderline iron stores undergoing a strong catch-up-growth erythropoietic response.
  • Counter-evidence on record: This is an animal, hypophysectomy-model finding; no human ferritin, transferrin saturation, or hemoglobin data in mecasermin-treated patients were located during this review.

Regulatory status

Not addressed in the Increlex label [1]; iron studies or ferritin monitoring are not specified.

Population evidence

Hypophysectomized rats given recombinant human IGF-1 showed increased 59Fe incorporation into erythrocytes alongside a reticulocyte rise, a directly measured functional marker of increased iron utilization for hemoglobin synthesis, not a marker of iron loss [4]. See Overlap map: this shares its source with the Oxygen delivery/utilization entry above.

Mechanism

Named: increased erythropoiesis (Step 2, category I, increased utilization) raises iron demand for hemoglobin synthesis; this is the standard physiology of any erythropoiesis-stimulating exposure, not a mecasermin-specific iron-handling defect.

Counter-evidence held on record

This is an increased-utilization signal tied to enhanced red-cell production, not an iron-deficiency claim, and does not support a standing iron supplementation recommendation.

Copper

Not graded — disclosed evidence gap

See study details

Copper

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. ungraded

Limits on what this shows

  • Why no grade: Both conditions for ungraded were met: no Tier B or Tier C mechanistic evidence linking IGF-1 or mecasermin to copper metabolism or ceruloplasmin was located despite dedicated queries, and no circulating consumer claim about mecasermin and copper was found either. This was searched directly (mecasermin/IGF-1 plus copper and ceruloplasmin) and via the Step 2 mechanism classes (absorption interference, cofactor antagonism), none of which surfaced a copper-specific finding for this drug or its class. Access note: PubMed, Europe PMC, OpenAlex, and Semantic Scholar were rate-limited or blocked for large portions of this review; only Crossref's metadata search remained reliably reachable, so this should be treated as a disclosed tooling limitation as well as a literature gap, and re-checked in a future revision with full search-channel access.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk, class-level signal only

Yellow — Low

See study details

A 2020 review specifically addresses crosstalk between the growth hormone/IGF-1 axis and the gut microbiome, indicating the topic is an active area of study for this hormone axis, but the review is not mecasermin-specific and its content was not verified beyond the bibliographic title during this review.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class/species extrapolation (Tier C) where at least one related study exists but this drug or this species was not directly studied; also used for context flags and reverse-direction (protective or retention) findings. yellow

Limits on what this shows

  • Key negative/null findings: Not accessible during this review.
  • At-risk subgroups: Not established.
  • Counter-evidence on record: None accessible; this entry is graded yellow rather than ungraded solely because a Tier C class-level source was located by title, per Step 7's instruction that any located Tier B/C source bars an ungraded assignment. A revision of this dossier should re-attempt full-text retrieval of this source specifically.

Regulatory status

Not addressed in the Increlex label [1].

Population evidence

"Crosstalk between the growth hormone/insulin-like growth factor-1 axis and the gut microbiome: A new frontier for microbial endocrinology" [13]. This is disclosed explicitly as a title-only citation: repeated attempts to retrieve its abstract or full text were blocked by rate limiting on PubMed, Europe PMC, and Crossref's abstract field during this review, so its specific findings are not summarized here and are not used beyond establishing that class-level literature on this axis exists.

Mechanism

Not verified in this review; disclosed as an evidence gap pending full-text access.

Counter-evidence held on record

This is a disclosed evidence gap dressed as a yellow grade only because of the located title, not a characterized microbiome effect. No probiotic or microbiome-support recommendation is made on this basis.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

Oxygen delivery/utilization, theoretical stimulation of erythropoiesis

Yellow — Low

See study details

Recombinant human IGF-1 restored red-cell production in hypophysectomized rats, raising reticulocyte counts to a degree similar to growth hormone; this is an animal finding, not a measured human hemoglobin or hematocrit outcome for mecasermin.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class/species extrapolation (Tier C) where at least one related study exists but this drug or this species was not directly studied; also used for context flags and reverse-direction (protective or retention) findings. yellow

Limits on what this shows

  • Key negative/null findings: None identified for mecasermin specifically; no human severe-primary-IGFD cohort study measuring hemoglobin or hematocrit during Increlex therapy was located during this review.
  • At-risk subgroups: None established; this is a mechanistic, animal-model finding only.
  • Counter-evidence on record: This is a rodent, hypophysectomy-model finding, not a mecasermin-treated human outcome, and severe primary IGFD is not equivalent to surgical hypophysectomy; extrapolation to the labeled population is uncertain.

Regulatory status

Not addressed in the Increlex label [1]; hemoglobin/hematocrit monitoring is not specified.

Population evidence

Hypophysectomized rats given subcutaneous recombinant human IGF-1 (120 µg/day) showed increases in body weight, reticulocyte count, and radiolabeled iron (59Fe) incorporation into erythrocytes similar in magnitude to growth hormone infusion; IGF-1 stimulated erythropoiesis before serum erythropoietin itself rose, implying both direct and erythropoietin-mediated mechanisms [4]. A further study reported enteral IGF-1 also stimulated erythropoiesis [5] (title-level citation only, not opened beyond the bibliographic record).

Mechanism

Named: IGF-1 acts on erythroid progenitor cells both directly and by enhancing erythropoietin production, restoring red-cell formation lost after hypophysectomy [4].

Counter-evidence held on record

This is a potential-benefit direction (enhanced red-cell formation), not a deficiency, and does not support any oxygen-delivery-related supplement recommendation.

ATP production

Not graded — disclosed evidence gap

See study details

ATP production

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. ungraded

Limits on what this shows

  • Why no grade: Both conditions for ungraded were met: dedicated searches for IGF-1 and mitochondrial ATP synthesis or cellular energy output returned only unrelated hepatocyte-receptor-expression papers and one now-retracted cardiac-mitochondrial study (see Fails verification), none of which support even a yellow grade for ATP production specifically as distinct from the separately graded Mitochondrial burden entry. No circulating consumer "low energy" or ATP-depletion claim specific to mecasermin was identified either, consistent with this being a narrow orphan-drug population with limited consumer-facing depletion content. Access note: this category was searched across the same constrained channel set described under Copper above; a future revision should re-attempt PubMed and Europe PMC directly once access is unblocked.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

  • Calcium / bone health

    Where it comes from: General consumer framing that growth-hormone-axis therapies "deplete calcium" or "weaken bone," extrapolated from generic hormone-depletion lists.

    Why it fails: Directly contradicted by Tier C bone-marker data: rhIGF-1 and GH therapy in GH-deficient adults raised bone-formation alkaline phosphatase [10, 11], consistent with increased bone-building activity, the opposite of depletion. No study reviewed showed a calcium deficit; the drug's own anabolic mechanism runs the other direction.

  • Mitochondrial / cardiac protection

    Where it comes from: A study reporting IGF-1 alleviates high-fat-diet-induced myocardial contractile dysfunction, which would otherwise be cited as evidence of a mitochondrial-protective effect.

    Why it fails: The article has been formally retracted [16]. A retracted study cannot support a claim in either direction and is listed here specifically so a reader who encounters the original title elsewhere knows it has been withdrawn.

  • Hypoglycemia as "nutrient deficiency"

    Where it comes from: Generic consumer-health framing that treats a medication's hypoglycemia warning as evidence of a depleted nutrient (a "blood sugar crash").

    Why it fails: The label attributes mecasermin's hypoglycemia specifically to insulin-receptor-mediated suppression of hepatic glucose production and stimulation of peripheral glucose utilization [1], the drug's own intended pharmacodynamic action (per Hard Rule 2, a clinical/pharmacologic outcome), not a measured deficiency of any nutrient.

All references used above
  1. Increlex (mecasermin) injection, solution, prescribing information. — Ipsen Biopharmaceuticals, Inc. FDA-approved labeling, DailyMed.
  2. WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index, code H01AC03 (mecasermin).
  3. Møller J, Jørgensen JOL, Marqversen J, Frandsen E, Christiansen JS. Insulin-like growth factor I administration induces fluid and sodium retention in healthy adults: possible involvement of renin and atrial natriuretic factor. — Clinical Endocrinology, 2000. DOI 10.1046/j.1365-2265.2000.00931.x. Tier B (rhIGF-1, healthy adults, not the labeled IGFD population). Abstract opened via Crossref metadata.
  4. Kurtz A, Zapf J, Eckardt KU, Clemons G, Froesch ER, Bauer C. Insulin-like growth factor I stimulates erythropoiesis in hypophysectomized rats. — Proceedings of the National Academy of Sciences, 1988. DOI 10.1073/pnas.85.20.7825. Tier B (recombinant human IGF-1, rat model). Abstract opened via Crossref metadata.
  5. Kling PJ, Taing KM, Dvorak B, Woodward SS, Philipps AF. Insulin-like growth factor-I stimulates erythropoiesis when administered enterally. — Growth Factors, 2006. DOI 10.1080/08977190600783162. Tier C.Title/bibliographic metadata only; full text or abstract not retrieved during this review.
  6. Bechensteen AG, Halvorsen S. Insulin-like Growth Factor 1 and Erythropoiesis During Growth. — In: Pathophysiology and Pharmacology of Erythropoietin, 1992. DOI 10.1007/978-3-642-77074-6_9. Tier C.Title only; not opened.
  7. Guilland-Cumming DF, Bevington A, Russell RGG. Effect of insulin and insulin-like growth factor-1 on phosphate uptake in MG-63 cells. — Bone and Mineral, 1992. DOI 10.1016/0169-6009(92)92134-c. Tier C, in vitro.Title only; not opened.
  8. Condamine L, Friedlander G, Garabédian M. Phosphate deprivation and insulin-like growth factor 1 directly stimulate 1,25(OH)2 vitamin D3 synthesis in cultured kidney cells. — Bone and Mineral, 1992. DOI 10.1016/0169-6009(92)91743-3. Tier C, in vitro.Title only; not opened.
  9. Bikle DD. Growth Hormone/Insulin-Like Growth Factor-1/PTH Axis in Bone. — Journal of Bone and Mineral Research, 2008. DOI 10.1359/jbmr.080111. Tier C review.Title only; not opened.
  10. Bianda T, Schmid C. Bone Alkaline Phosphatase During Short-Term Treatment with Insulin-like Growth Factor I and Growth Hormone in Growth Hormone-Deficient Adults. — Journal of Bone and Mineral Research, 1998. DOI 10.1359/jbmr.1998.13.4.759. Tier C (GH-deficient adults, not primary IGFD).Title only; not opened.
  11. Magnusson P, Degerblad M, Säaf M, Larsson L, Thorén M. Different Responses of Bone Alkaline Phosphatase Isoforms During Recombinant Insulin-like Growth Factor-I (IGF-I) and During Growth Hormone Therapy. — Journal of Bone and Mineral Research, 1997. DOI 10.1359/jbmr.1997.12.2.210. Tier C.Title only; not opened.
  12. Seidelin M, Madsen SS. Endocrine control of Na+,K+-ATPase and chloride cell development in brown trout. — Journal of Endocrinology, 1999. DOI 10.1677/joe.0.1620127. Tier C, cross-species (teleost fish).
  13. Jensen EA, Young JA, Mathes SC, List EO, Carroll RK, Kuhn J, Onusko M, Kopchick JJ, Murphy ER, Berryman DE. Crosstalk between the growth hormone/insulin-like growth factor-1 axis and the gut microbiome: A new frontier for microbial endocrinology. — Growth Hormone & IGF Research, 2020. DOI 10.1016/j.ghir.2020.101333. Tier C review, not mecasermin-specific.Title only; abstract/full text fetch blocked by rate limiting during this review.
  14. Laron Z, Werner H. Congenital IGF-1 deficiency protects from cancer: lessons from Laron syndrome. — Endocrine-Related Cancer, 2023. DOI 10.1530/erc-22-0394. Tier C (deficiency-state literature in the population mecasermin treats).Title and an indexed summary only; full text not opened during this review.
  15. Cappa M, et al. Profile of mecasermin for the long-term treatment of growth failure in children and adolescents with severe primary IGF-1 deficiency. — Therapeutics and Clinical Risk Management, 2009. DOI 10.2147/TCRM.S6178. Tier A/B, drug-specific review.Only a single abstract sentence was retrievable via the publisher page; full text was not obtained (404 on direct PDF link).
  16. Editorial retraction of: Insulin-Like Growth Factor 1 Alleviates High-Fat Diet-Induced Myocardial Contractile Dysfunction. — Hypertension, 2022. DOI 10.1161/hyp.0000000000000219. Cited only as a retraction flag for Fails verification.
  17. Chernausek SD, et al. Long-Term Treatment with Recombinant Insulin-Like Growth Factor (IGF)-I in Children with Severe IGF-I Deficiency due to Growth Hormone Insensitivity. — Journal of Clinical Endocrinology & Metabolism, 2007. DOI 10.1210/jc.2006-1610. This is the pivotal mecasermin trial literature and is the single highest-value source not obtained in this review.Located via Crossref bibliographic search only; every attempt to fetch its abstract or full text returned HTTP 429 across multiple retries. Not cited as evidence anywhere above. Flagged for priority re-fetch in any revision of this dossier.
  18. Rosenbloom AL. Mecasermin (recombinant human insulin-like growth factor I). — Advances in Therapy, 2009. DOI 10.1007/s12325-008-0136-5.Located via Crossref bibliographic search only; fetch attempts returned HTTP 429. Not cited as evidence anywhere above.