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MyDeficiencies

Tesamorelin

GHRH analog (somatropin agonist, endocrine/pituitary axis)

Also sold as Egrifta, Egrifta SV, Egrifta WR.

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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.

Tesamorelin has no classical pharmacokinetic depletion mechanism. It is a 44-amino-acid peptide given by subcutaneous injection, with absolute bioavailability under 4%, an elimination half-life of roughly 8-11 minutes, and no oral or gastrointestinal absorption route at all, so the chelation, gastric-pH, bile-acid-sequestration, and transporter-competition mechanisms that drive depletion for orally dosed drugs do not apply. No formal human metabolism studies have been performed; the drug is not itself a cytochrome P450 substrate, though the growth hormone (GH) it stimulates can secondarily modulate CYP450-mediated clearance of other drugs, which is a drug-drug interaction, not a drug-nutrient one. Renal and hepatic impairment pharmacokinetics have never been established, and no food, mineral, or antacid interaction is documented for the drug itself.

GHRH analog (somatropin agonist, endocrine/pituitary axis) · ATC H01AC06 · also sold as Egrifta and Egrifta SV and Egrifta WR · reviewed 2026-09-28. 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 Tesamorelin in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low
Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
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: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

IGF-1 elevation and glucose intolerance, GH-axis pharmacologic effect

Orange — Moderate

See study details

Tesamorelin's intended mechanism, pulsatile stimulation of endogenous GH, produces dose-related IGF-1 elevation and a real, quantified increase in glucose intolerance/diabetes risk at the approved 2 mg dose; this is the drug doing what it is designed to do, not a vitamin or mineral deficiency, and is included here because it is the single most consequential metabolic signal tied to this drug's mechanism.

Full detail, limits and 2 references

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. orange

Limits on what this shows

  • Key negative/null findings: Baker LD et al., "Effects of Growth Hormone-Releasing Hormone on Cognitive Function," JAMA Neurology 2012, PMID 22869065 (Tier A, drug-specific, n=152, 1 mg/day tesamorelin, 20 weeks, in a healthy-older-adult/MCI population, not HIV lipodystrophy): fasting plasma glucose, HbA1c, and 2-hour OGTT glucose and insulin were "not affected" despite IGF-1 rising into the physiological range. This suggests the glucose-intolerance signal is dose- and population-bound (evident at the approved 2 mg dose in a population with HIV/antiretroviral-related metabolic risk, not clearly present at 1 mg in a metabolically healthier population).
  • At-risk subgroups: Patients with obesity, prediabetes, or a family history of diabetes per the label; the approved 2 mg HIV-lipodystrophy population specifically, where antiretroviral therapy itself often independently affects glucose metabolism (confounding by indication/comorbidity is plausible and not fully excluded by the located sources).

Regulatory status

EGRIFTA WR label, Section 5.2: at 26 weeks, 47% of patients had IGF-1 >2 SD above the age-adjusted mean and 36% had >3 SD; at 52 weeks, 34% and 23% respectively. Section 5.4: 5% of EGRIFTA-treated patients vs. 1% placebo developed HbA1c ≥6.5%; hazard ratio for diabetes development 3.3 (95% CI 1.4-9.6). Monitoring of fasting glucose pre-treatment and periodically thereafter is a labeled requirement.

Population evidence

FDA Division Director Summary Review, NDA 022505 (2010, Tier A, pooled pivotal-trial population): baseline mean HbA1c 5.26% (tesamorelin) and 5.28% (placebo), increasing 0.14% vs. 0.02% respectively over the trial. Clarke RE et al. (Falutz J, senior author), "Safety and metabolic effects of tesamorelin...in patients with type 2 diabetes," PLOS ONE 2017, PMID 28617838: randomized, placebo-controlled, n=53 (16 placebo, 18 tesamorelin 1 mg, 19 tesamorelin 2 mg), 12 weeks. IGF-1 rose dose-dependently (1 mg +33 ng/mL, 2 mg +66 ng/mL, P<0.05 vs. placebo); HbA1c change differed significantly between placebo and the 2 mg group at week 12 (P<0.05), though the 1 mg group's HbA1c improved rather than worsened, and the trial's primary endpoint (relative insulin response) showed no significant between-group difference.

Mechanism

Named: this is tesamorelin's direct, intended pharmacologic action. GH and IGF-1 have well-established insulin-antagonist effects, reducing peripheral insulin sensitivity; this is the same axis effect used therapeutically to reduce visceral fat.

Counter-evidence held on record

The MCI trial (Baker 2012) is itself real, drug-specific counter-evidence at the lower dose and in a different population; the T2D dose-finding trial's 1 mg arm also improved HbA1c rather than worsening it, complicating a simple dose-response story. This is the drug's own labeled pharmacologic effect, not a nutrient or mineral deficiency, and no vitamin, mineral, or antioxidant supplementation addresses it. Glucose and IGF-1 monitoring, and any dose adjustment, are prescriber decisions.

  • Clarke RE, Verma N, Sherman C, Falutz J, et al. Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: a randomized, placebo-controlled trial. — Randomized, placebo-controlled, n=53 (16 placebo, 18 tesamorelin 1 mg, 19 tesamorelin 2 mg), 12 weeks plus 4-week follow-up. Source for the IGF-1/glucose entry's dose-response and HbA1c data.
  • Baker LD, Barsness SM, Borson S, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. — Randomized, double-blind, placebo-controlled, n=152 (66 with MCI, 76 healthy of the 137 completers), tesamorelin 1 mg/day, 20 weeks plus 10-week washout. Source for the lower-dose/different-population null glucose and fluid-retention findings used as counter-evidence.

Fluid retention

Orange — Moderate

See study details

Tesamorelin produces dose-related fluid retention, manifesting as edema, arthralgia, myalgia, and carpal-tunnel-type symptoms, attributed in the label to induction of GH secretion; this is an excess/retention-direction effect, not a sodium or mineral depletion.

Full detail and limits

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. orange

Limits on what this shows

  • Key negative/null findings: Baker et al. 2012 (1 mg dose, MCI/healthy population, 20 weeks): "objective weight measures showed no difference between groups" and no coronary adverse events were observed, consistent with the effect being bounded to the higher approved 2 mg dose and/or the HIV-lipodystrophy population.
  • At-risk subgroups: Patients on the approved 2 mg dose; the label notes the effect is "usually transient" and does not stratify by additional risk factors such as pre-existing edema-prone states.

Regulatory status

EGRIFTA WR label, Section 5.3: fluid retention "may occur during therapy and is thought to be related to induction of GH secretion," manifesting as edema, arthralgia, and carpal tunnel syndrome, "typically transient or resolve upon discontinuation." Table 1 (26-week phase, N=543 tesamorelin vs. N=263 placebo): peripheral edema 6% vs. 2%, arthralgia 13% vs. 11%, myalgia 6% vs. 2%, injection-site reactions 17-25% vs. 6-14%.

Population evidence

CADTH Clinical Review Report, Tesamorelin (Egrifta), NCBI Bookshelf NBK539127 (Tier A, drug-specific, pooled pivotal trials): edema reported in 9.9% of tesamorelin-treated patients vs. 5.8% placebo in the LIPO-010 trial, and 5.2% vs. 0.8% in the CTR-1011 trial.

Mechanism

Named but not independently re-verified for tesamorelin specifically in this review: the label attributes the effect to GH induction; GH itself is documented (in the companion somatropin dossier's independently verified sources) to activate renal epithelial sodium channels via a renin-aldosterone-like pathway, producing sodium and water retention. That specific channel-level mechanism paper was not re-opened for this tesamorelin review (see access notes); it is cited here only as class-level mechanistic context, not as tesamorelin-specific evidence.

Counter-evidence held on record

No source located suggests tesamorelin causes sodium or fluid loss; direction is consistently retention across the label, the CADTH pooled-trial data, and (by absence of a signal at lower dose) the MCI trial. This is a retention/excess-fluid risk, not a depletion. Sodium or fluid supplementation is not indicated and could worsen retention. Symptomatic edema, arthralgia, or carpal-tunnel symptoms should go to the prescriber for dose review, not to independent dietary changes.

No entry is ungraded in this revision

Not graded — disclosed evidence gap

See study details

Iron and Oxygen delivery/utilization were left ungraded in the prior version of this dossier because the one class-level lead for each (Vihervuori et al. 1997 for Iron, Miniero et al. 2012 for Oxygen delivery/utilization) could not be independently opened: the Wiley Online Library page and the PubMed abstract page each returned only an access error or a bot-verification skeleton, and the Europe PMC, Semantic Scholar, and OpenAlex search endpoints were all rate-limited. This revision re-attempted both categories with a fresh, dedicated effort across PubMed, Europe PMC, Semantic Scholar, OpenAlex, Crossref, and Unpaywall; the search-style endpoints on most of those hosts were still blocked or rate-limited, but a direct, single-record OpenAlex API lookup by DOI succeeded for both sources, returning each paper's actual indexed abstract. Both categories now qualify for a yellow, class-extrapolation grade (see Graded entries: yellow above) and neither remains ungraded.

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. empty section

Limits on what this shows

  • Why no grade: Not applicable: this section is empty because both categories previously blocked by tooling access now have real Tier C evidence, not because a search was skipped. Iron and Oxygen delivery/utilization both graded yellow, each with a source actually opened (its abstract retrieved and read) during this revision (see Sources).

What would reopen this section

A future finding that either newly graded entry rested on a source that turns out not to include recombinant GH (or a closer GH-axis agent) in the studied cohort, or a correction to the OpenAlex-reconstructed abstract text against the full paper once it can be independently opened, either of which would require re-evaluating that entry rather than leaving the section as printed here.

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, hepatic reverse-direction gene-expression signal

Yellow — Low

See study details

In the one randomized, placebo-controlled trial that directly measured a mitochondria-related outcome in tesamorelin-treated patients, tesamorelin increased, rather than decreased, expression of hepatic oxidative-phosphorylation genes, a reverse-direction signal at the transcript level, not a measured functional deficit or a burden.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. yellow

Limits on what this shows

  • Key negative/null findings: None identified specifically contradicting this finding. An important caveat, not a null finding: this is gene-expression (transcript-level) evidence, not a measured functional outcome such as respiratory-chain enzyme activity or 31P-MRS-measured ATP resynthesis kinetics (the kind of direct functional measurement used for somatropin in the companion dossier); no such functional study of tesamorelin was located.
  • At-risk subgroups: None identified. The finding is specific to liver tissue in HIV-associated NAFLD; it has not been examined in skeletal muscle or other tissue, or in HIV-lipodystrophy patients without NAFLD.

Regulatory status

Not addressed in the FDA label.

Population evidence

Stanley TL et al., "Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD," JCI Insight 2020, PMID 32701508 (opened and read in full for this review). Substudy of a 12-month randomized, double-blind, placebo-controlled trial of tesamorelin 2 mg/day vs. placebo in HIV-associated non-alcoholic fatty liver disease, with paired pre/post liver biopsies in 18 tesamorelin-treated and 21 placebo-treated participants (n=39). Gene set enrichment analysis found the oxidative-phosphorylation hallmark gene set significantly upregulated by tesamorelin vs. placebo (normalized enrichment score 1.94, FDR q=0.0005), with leading-edge genes spanning electron-transport-chain complexes I-V: NDUFA6 and NDUFB1 (complex I), SDHC and SDHD (complex II), UQCR10 and UQCRH (complex III), COX7A2L and COX17 (complex IV), ATP5PF and ATP5F1C (complex V).

Mechanism

Named: change in oxidative-phosphorylation gene expression correlated with change in hepatic IGF-1 transcription (r=0.35, P=0.03), change in serum IGF-1 (r=0.45, P=0.005), and inversely with change in visceral fat content (r=-0.42, P=0.008), consistent with GH/IGF-1-axis-driven hepatic mitochondrial gene upregulation accompanying visceral-fat and hepatic-steatosis reduction.

Counter-evidence held on record

No tesamorelin study located shows mitochondrial impairment. The same paper's introduction cites general NAFLD pathophysiology literature stating that "mitochondrial impairment may promote hepatic fat accumulation...increasing oxidative stress" as background on disease mechanism generally; that sentence describes NAFLD pathophysiology, not a tesamorelin treatment effect, and is not counted as evidence for or against this entry. This is a reverse-direction (potentially favorable), transcript-level signal in liver tissue only, not a confirmed functional mitochondrial outcome and not a basis for any supplement claim in either direction.

  • Stanley TL, Fourman LT, Zheng I, et al. Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD. — RCT substudy, paired liver biopsies n=39 (18 tesamorelin, 21 placebo), 12 months, tesamorelin 2 mg/day vs. placebo. Source for the Mitochondrial burden and ATP production entries (oxidative-phosphorylation gene-set upregulation, NES 1.94, FDR q=0.0005).

Oxidative Stress

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

Oxidative stress, class-extrapolated reverse-direction signal

Yellow — Low

See study details

No oxidative-stress-marker study of tesamorelin itself was located. The closest available evidence, a small study of recombinant GH (a different drug in the same ATC class, H01AC) in GH-deficient children, found total antioxidant capacity rose, not fell, over 12 months of treatment.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. yellow

Limits on what this shows

  • Key negative/null findings: None located in the opposite direction, for either tesamorelin or the class.
  • At-risk subgroups: Cannot be determined from class-level pediatric data alone.

Regulatory status

Not addressed in the FDA label; not addressed for any drug in this class.

Population evidence

Pankratova MS et al., "Imbalance in the blood antioxidant system in growth hormone-deficient children before and after 1 year of recombinant growth hormone therapy," PeerJ 2015;3:e1055 (opened and read in full for this review). Cohort test: this study administered recombinant GH (0.033 mg/kg/day subcutaneously), NOT tesamorelin; it is Tier C class extrapolation for tesamorelin, not primary evidence. n=11 treatment-naive GH-deficient children (2 girls, 9 boys, ages 3-9) vs. 11 healthy prepubertal controls, 12 months of therapy. Total antioxidant capacity (TAC) rose significantly, from 525±166 to 658±115 µmol/L (P=0.0205); TAC was significantly lower in GHD children than controls before treatment.

Mechanism

Not established for tesamorelin directly. Plausible only insofar as tesamorelin's downstream effect (raised circulating GH and IGF-1) overlaps with the axis manipulated in the cited study, but by a materially different route: pulsatile stimulation of endogenous, physiologic GH release (tesamorelin) versus fixed-dose exogenous GH replacement (recombinant GH), and in a different population (pediatric GH deficiency vs. adult HIV-associated lipodystrophy).

Counter-evidence held on record

The cited study itself is a reassuring, not concerning, direction; no source in either the tesamorelin-specific or class-level literature located during this review suggests worsened oxidative stress from GH-axis stimulation. Tier C, small (n=11), pediatric, different drug in the same ATC class; mechanism plausible only via a shared downstream axis reached by a different route. Not a basis for antioxidant supplementation in either direction.

Copper and Iron Balance

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

Copper, class-extrapolated, no confirmed deficit

Yellow — Low

See study details

No tesamorelin-specific copper study was located. The same class-level recombinant-GH study found ceruloplasmin, the principal copper-status marker, already elevated at baseline and trending down non-significantly after 12 months, not a confirmed deficit.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. yellow

Limits on what this shows

  • Key negative/null findings: The ceruloplasmin change in the cited study was non-significant; this is itself the key null result, and it is drawn from the same small, pediatric, different-drug cohort noted above. A related class-level study on zinc in a similarly designed cohort (Richards & Marshall, GH-deficient children given pituitary-derived GH, opened and read in full for this review: "no significant changes in zinc concentration were observed with GH treatment" in serum, urine, or hair over up to two years) found a similar pattern of no confirmed trace-mineral deficit with GH-axis stimulation, offered here as supporting context rather than as its own graded entry.
  • At-risk subgroups: Cannot be determined from the available class-level evidence.

Regulatory status

Not addressed in the FDA label; not addressed for any drug in this class.

Population evidence

Pankratova MS et al., PeerJ 2015;3:e1055 (same source and cohort as the Oxidative stress entry; see Overlap map; opened and read in full for this review). Cohort test: recombinant GH, NOT tesamorelin; Tier C class extrapolation. Ceruloplasmin was elevated at baseline in the GHD children relative to controls (581±100 vs. 518±70 µg/mL) and decreased non-significantly after 12 months of GH therapy, to 531±111 µg/mL. The authors note that an elevated ceruloplasmin can itself reflect inflammatory processes, complicating interpretation as a pure copper-status marker.

Mechanism

Not established for tesamorelin; class-level plausibility only, via the shared downstream GH/IGF-1 axis (same caveat on route/population as the Oxidative stress entry).

Counter-evidence held on record

The one class-level study with a real copper-status marker found no significant chronic deficit; a related class-level zinc study in a comparable population found the same pattern for a different trace mineral. Tier C, small, pediatric, different drug in the same ATC class; not a basis for copper supplementation.

Iron, class-extrapolated marker shift during GH-axis-stimulated growth

Yellow — Low

See study details

No tesamorelin-specific iron, ferritin, or hemoglobin study was located. The closest available evidence, a study of recombinant GH (a different drug in the same ATC class) in short-stature children undergoing GH-driven accelerated growth, found a transient ferritin fall with only a slight rise in the more function-specific soluble transferrin receptor, and no increase in anemia or microcytosis.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. yellow

Limits on what this shows

  • Key negative/null findings: The soluble transferrin receptor result is itself the key bounding finding: it moved only slightly and anemia/microcytosis did not increase, indicating a store-level marker shift rather than a confirmed functional iron deficiency, even at the class level. No tesamorelin-specific hematologic or iron panel was found in the FDA's 2010 Division Director Summary Review or in any tesamorelin trial read in full for this review (T2D RCT, MCI RCT, NAFLD RCT and its transcriptomic and proteomic substudies).
  • At-risk subgroups: Cannot be determined for tesamorelin from class-level pediatric short-stature data alone.

Regulatory status

Not addressed in the FDA label; not addressed for any drug in this class. Iron status monitoring is not a labeled requirement for tesamorelin.

Population evidence

Vihervuori E, Cook JD, Siimes MA, "Iron status of children with short stature during accelerated growth due to growth hormone treatment," Acta Paediatr 1997, DOI 10.1111/j.1651-2227.1997.tb08939.x, PMID 9202792. Abstract retrieved and read this session via the OpenAlex API's single-record DOI lookup, which reconstructs the indexed abstract from its stored abstract_inverted_index (direct fetch of the Wiley Online Library article page itself returned an HTTP 403 error, so this is the abstract, not the full paper). Cohort test: recombinant GH (rhGH), NOT tesamorelin; Tier C class extrapolation. n=35 children with short stature given 6 months of GH treatment. Serum ferritin fell from 29.6 to 19.7 micrograms/L, with most of the change occurring in the first week; soluble transferrin receptor, the marker more specific to functional (tissue-level) iron deficiency, rose only slightly, from 7.12 to 7.51 mg/L. No increase in the prevalence of anemia or microcytosis was reported.

Mechanism

Not established for tesamorelin; class-level plausibility only. GH/IGF-1-driven erythropoiesis and accelerated linear growth increase iron demand and turnover, transiently lowering ferritin stores, in a study population given direct exogenous GH replacement rather than tesamorelin's indirect, pulsatile stimulation of endogenous GH release, and in short-stature children rather than adults with HIV-associated lipodystrophy.

Counter-evidence held on record

The cited study's own functional marker (soluble transferrin receptor) barely moved and anemia/microcytosis did not increase, so even at the class level this is a bounded finding, not a clear deficit. No source located, for tesamorelin or the class, reports iron overload with GH-axis stimulation. Tier C, class extrapolation from a different drug (rhGH, not a GHRH analog) in a different population (pediatric short stature, not adult HIV-lipodystrophy), reached by a different pharmacologic route. Not a basis for iron supplementation; a real deficit was not confirmed even in the class-level source, and iron repletion without a measured deficit carries its own overload risk.

  • Vihervuori E, Cook JD, Siimes MA. Iron status of children with short stature during accelerated growth due to growth hormone treatment. — Prospective observational study, n=35 children with short stature, 6 months of recombinant GH (NOT tesamorelin). Cohort-tested and confirmed as a class-extrapolation (Tier C) source for the Iron entry. Abstract reconstructed and read via the OpenAlex API's single-record DOI lookup (its abstract_inverted_index) this session; the Wiley Online Library article page itself returned an HTTP 403 error on direct fetch, so only the abstract, not the full paper, was opened.Cohort excluded tesamorelin; recombinant GH (H01AC01), not a GHRH analog. Used only as class-level mechanistic context, clearly labeled as such in the Iron entry. Full paper not opened; abstract only, retrieved via OpenAlex.

Gut Microbiome Risk

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

Gut microbiome risk, mechanism-only, direction uncertain

Yellow — Low

See study details

Genetic deletion of the hepatic growth hormone receptor alters mouse gut microbiota composition and bile-acid metabolism, indicating the GH axis affects the microbiome; tesamorelin adds GH signaling rather than removing it, so the direction of any tesamorelin-specific effect cannot be inferred from this model.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. yellow

Limits on what this shows

  • Key negative/null findings: No human data located. No study administering tesamorelin, or any GHRH analog, and measuring microbiome composition was found despite a genuine search across PubMed and Europe PMC query attempts (see access notes).
  • At-risk subgroups: Cannot be determined from available evidence.

Regulatory status

Not addressed in the FDA label; no microbiome monitoring is recommended.

Population evidence

Yu Z, Wang Y, Zhang F, et al., "Deletion of hepatic growth hormone receptor (GHR) alters the mouse gut microbiota by affecting bile acid metabolism," Gut Microbes 2023, DOI 10.1080/19490976.2023.2221098 (opened and read via its DOAJ-hosted full text for this review). Mouse model with tissue-specific GHR knockout in liver (LKO) and adipose tissue (AKO), i.e., loss of GH signaling in a specific tissue, the opposite manipulation from tesamorelin's GH-stimulating action. Hepatic (not adipose) GHR deletion altered gut microbial composition (Bacteroidota/Firmicutes phylum-level shifts; Lactobacillus, Muribaculaceae, and Parasutterella genus-level shifts) without changing alpha-diversity, mediated by an altered bile-acid pool (increased 12-OH/non-12-OH bile-acid ratio via increased CYP8B1 expression) and increased microbial short-chain fatty acid production.

Mechanism

Named but indirect and opposite-direction: hepatic GH signaling shapes bile-acid composition, which in turn shapes the gut microbial community. Demonstrated by removing GH signaling, not by adding exogenous GH stimulation as tesamorelin does.

Counter-evidence held on record

None found in either direction in humans, or in a GH-agonism (rather than GH-loss) animal model. Direction of effect for actual GH-axis stimulation (tesamorelin's mechanism) cannot be inferred from a receptor-loss model. Treat as biological plausibility only, not as evidence of risk.

  • Yu Z, Wang Y, Zhang F, et al. Deletion of hepatic growth hormone receptor (GHR) alters the mouse gut microbiota by affecting bile acid metabolism. — Mouse hepatic/adipose GHR-knockout model (loss of GH signaling), not exogenous GH or GHRH-analog administration. Source for the Gut microbiome risk entry.

Oxygen and ATP Output

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

ATP production, hepatic reverse-direction gene-expression signal

Yellow — Low

See study details

The same trial's gene-expression data show the complex V (ATP synthase) genes ATP5PF and ATP5F1C among the genes upregulated by tesamorelin, a reverse-direction signal specific to ATP-synthesis machinery gene expression, not a measured ATP-flux outcome.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. yellow

Limits on what this shows

  • Key negative/null findings: No study located found reduced ATP-synthesis gene expression or measured ATP output with tesamorelin. This entry's central caveat is that it is transcript-level evidence; no direct functional ATP-production measurement (such as 31P-MRS phosphocreatine recovery kinetics) has been performed for tesamorelin, which is a real, disclosed gap in the direct-measurement sense even though the transcript-level signal itself is Tier A and drug-specific.
  • At-risk subgroups: None identified; liver-tissue-specific finding in HIV-associated NAFLD.

Regulatory status

Not addressed in the FDA label.

Population evidence

Stanley TL et al., JCI Insight 2020, PMID 32701508 (same source and cohort as the Mitochondrial burden entry; see Overlap map). ATP5PF and ATP5F1C, encoding subunits of mitochondrial complex V (ATP synthase), were among the leading-edge genes in the upregulated oxidative-phosphorylation gene set (NES 1.94, FDR q=0.0005).

Mechanism

Same as the Mitochondrial burden entry: correlated with hepatic and serum IGF-1 change and inversely with visceral-fat change, consistent with GH/IGF-1-axis-driven upregulation.

Counter-evidence held on record

No study found in the opposite direction (i.e., no evidence of tesamorelin-impaired ATP-synthesis gene expression). Presented as a reverse-direction transcript-level signal only, not a confirmed functional ATP-production outcome, and not a basis for any supplement or energy-metabolism claim.

  • Stanley TL, Fourman LT, Zheng I, et al. Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD. — RCT substudy, paired liver biopsies n=39 (18 tesamorelin, 21 placebo), 12 months, tesamorelin 2 mg/day vs. placebo. Source for the Mitochondrial burden and ATP production entries (oxidative-phosphorylation gene-set upregulation, NES 1.94, FDR q=0.0005).

Oxygen delivery / utilization, class-extrapolated reverse-direction signal

Yellow — Low

See study details

No tesamorelin-specific hemoglobin or hematocrit study was located. The closest available evidence, a large retrospective study of recombinant GH in children with GH-deficiency-related anemia, found hemoglobin rose significantly toward normal after rhGH therapy, a reverse-direction (corrective) signal, not a depletion.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. yellow

Limits on what this shows

  • Key negative/null findings: None located in the opposite direction, for either tesamorelin or the class. As with Iron, no tesamorelin-specific hemoglobin or hematocrit data were found in the FDA's 2010 Division Director Summary Review or in any tesamorelin trial read in full for this review.
  • At-risk subgroups: Cannot be determined for tesamorelin from this pediatric, GH-deficient, anemic-at-baseline population; tesamorelin's own HIV-lipodystrophy population is not GH-deficient and is not addressed by this study.

Regulatory status

Not addressed in the FDA label; not a labeled indication for tesamorelin. GH deficiency is independently recognized as a cause of mild normocytic-normochromic anemia via reduced GH/IGF-1 stimulation of bone-marrow red-cell production.

Population evidence

Miniero R, Altomare F, Rubino M, Matarazzo P, Montanari C, Petri A, Raiola G, Bona G, "Effect of Recombinant Human Growth Hormone (rhGH) on Hemoglobin Concentration in Children With Idiopathic Growth Hormone Deficiency-related Anemia," J Pediatr Hematol Oncol 2012;34(6):407-11, DOI 10.1097/MPH.0b013e318253f082, PMID 22584781. Abstract retrieved and read this session via the OpenAlex API's single-record DOI lookup, reconstructed from its stored abstract_inverted_index (the individual PubMed abstract page returned only an automated bot-verification/metadata skeleton, and the journals.lww.com full-text page returned an HTTP 402 paywall error, so this is the abstract, not the full paper). Cohort test: recombinant GH (rhGH), NOT tesamorelin; Tier C class extrapolation. Retrospective multicenter study, n=279 children (196 boys) with isolated idiopathic GH deficiency; 48 of them (41 boys, 7 girls) had anemia before starting rhGH replacement therapy (hemoglobin standard-deviation score of -2.59 SD). Hemoglobin-SDS rose significantly (P<0.05) after 12 months of rhGH therapy and continued improving through 48 months of treatment (-0.39 SD), by which point all originally anemic children had normal hemoglobin values.

Mechanism

Named at the class level: the GH/IGF-1 axis stimulates bone-marrow erythropoiesis, and GH deficiency is an established, generally mild and reversible cause of normocytic anemia. Plausible for tesamorelin only insofar as tesamorelin also raises circulating GH and IGF-1, but by a materially different route: pulsatile stimulation of endogenous GH release in adults with HIV-associated lipodystrophy, who are not by definition GH-deficient, versus fixed-dose exogenous GH replacement in GH-deficient, anemic children.

Counter-evidence held on record

The cited study is itself a reassuring, corrective-direction finding; no source in either the tesamorelin-specific or class-level literature located during this review suggests worsened oxygen-carrying capacity from GH-axis stimulation. Tier C, class extrapolation from a different drug in a different population (GH-deficient, anemic children, not adult HIV-lipodystrophy patients), reached by a different route (exogenous replacement vs. tesamorelin's endogenous stimulation). Not a basis for any hematologic supplementation claim in either direction.

  • Miniero R, Altomare F, Rubino M, Matarazzo P, Montanari C, Petri A, Raiola G, Bona G. Effect of Recombinant Human Growth Hormone (rhGH) on Hemoglobin Concentration in Children With Idiopathic Growth Hormone Deficiency-related Anemia. — Retrospective multicenter study, n=279 children with isolated idiopathic GH deficiency (48 anemic at baseline), rhGH therapy (NOT tesamorelin), followed up to 48 months. Cohort-tested and confirmed as a class-extrapolation (Tier C) source for the Oxygen delivery/utilization entry. Abstract reconstructed and read via the OpenAlex API's single-record DOI lookup (its abstract_inverted_index) this session; the individual PubMed abstract page returned only an automated bot-verification/metadata skeleton, and journals.lww.com returned an HTTP 402 paywall error, so only the abstract, not the full paper, was opened.Cohort excluded tesamorelin; recombinant GH, a different drug in the same broad axis, not a GHRH analog. Used only as class-level mechanistic context, clearly labeled as such in the Oxygen delivery/utilization entry. Full paper not opened; abstract only, retrieved via OpenAlex.

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.

  • General "tesamorelin/GH peptide depletes vitamins and minerals" framing

    Where it comes from: Not attributable to any specific source found. Checked a mainstream clinical consumer reference (Mayo Clinic) and several peptide/fitness-marketing pages that specifically promote tesamorelin for off-label fat-loss and longevity use (Swolverine, Innerbody), where a depletion narrative would be expected to appear if it circulated.

    Why it fails: No consumer source, clinical reference, or peptide-marketing page located during this review made a specific "tesamorelin depletes X" claim, unlike commonly circulated narratives for metformin (B12), statins (CoQ10), or proton-pump inhibitors (B12/magnesium). The real, drug-specific effects found (fluid retention, IGF-1/glucose changes) run toward retention or the drug's own intended pharmacology, not toward a nutrient claim, and are graded above rather than left as an unsupported claim.

All references used above
  1. EGRIFTA WR (tesamorelin) for injection, US Prescribing Information. — FDA-approved labeling, warnings/precautions and clinical pharmacology sections.
  2. EGRIFTA/EGRIFTA SV (tesamorelin) US Prescribing Information, 2019. — Full label text: warnings and precautions, adverse reaction tables, clinical pharmacology, drug interactions.
  3. EGRIFTA WR (tesamorelin) US Prescribing Information, 2025. — Current label, checked for any newly added electrolyte, mineral, hematologic, or oxidative-stress content; none found beyond the 2019 label's scope.
  4. FDA Division Director Summary Review, NDA 022505 (EGRIFTA), 2010. — Most detailed regulatory safety document located; searched directly for hemoglobin, hematocrit, anemia, red blood cells, iron, ferritin, calcium, phosphate, sodium, potassium, magnesium, zinc, copper, and oxidative-stress content across the full pivotal-trial program. None found beyond glucose/HbA1c, IGF-1, and lipid data.
  5. WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index, H01AC06 Tesamorelin. — Confirms ATC classification (Somatropin and somatropin agonists) and the labeled HIV-lipodystrophy indication.
  6. Stanley TL, Fourman LT, Zheng I, et al. Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD. — RCT substudy, paired liver biopsies n=39 (18 tesamorelin, 21 placebo), 12 months, tesamorelin 2 mg/day vs. placebo. Source for the Mitochondrial burden and ATP production entries (oxidative-phosphorylation gene-set upregulation, NES 1.94, FDR q=0.0005).
  7. Stanley TL, related author group. Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach. — Plasma-protein substudy (n=44 paired, 20 tesamorelin/24 placebo) of the same parent RCT as the JCI Insight transcriptomic substudy above (see Overlap map). Confirms the same oxidative-phosphorylation upregulation finding and reports plasma VEGFA/TGFB1/CSF1 reductions correlating with NAFLD activity score improvement; the VEGFA/TGFB1/CSF1 findings were read but not used to support any graded entry in this dossier.
  8. Stanley TL, Fourman LT, Feldpausch MN, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. — Parent RCT, n=61 (26 tesamorelin, 28 placebo... cohort numbers as reported by the fetched summary; slight cohort-size variation across substudies reflects paired-sample subsets used in each analysis), 12 months, two academic centers. Read via its PMC record; contains no mitochondrial, oxidative-stress, iron, copper, or hematologic data itself.
  9. Clarke RE, Verma N, Sherman C, Falutz J, et al. Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: a randomized, placebo-controlled trial. — Randomized, placebo-controlled, n=53 (16 placebo, 18 tesamorelin 1 mg, 19 tesamorelin 2 mg), 12 weeks plus 4-week follow-up. Source for the IGF-1/glucose entry's dose-response and HbA1c data.
  10. CADTH. Clinical Review Report: Tesamorelin (Egrifta). — Health-technology-assessment review of the pivotal trial program (LIPO-010, CTR-1011 and others); source for pooled edema/fluid-retention adverse-event rates.
  11. Baker LD, Barsness SM, Borson S, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. — Randomized, double-blind, placebo-controlled, n=152 (66 with MCI, 76 healthy of the 137 completers), tesamorelin 1 mg/day, 20 weeks plus 10-week washout. Source for the lower-dose/different-population null glucose and fluid-retention findings used as counter-evidence.
  12. Pankratova MS, Ryzhkova EA, Nikankina LV, et al. Imbalance in the blood antioxidant system in growth hormone-deficient children before and after 1 year of recombinant growth hormone therapy. — Prospective observational study, n=11 treatment-naive GHD children vs. 11 healthy controls, 12 months of recombinant GH (NOT tesamorelin). Cohort-tested and confirmed as a class-extrapolation (Tier C) source for the Oxidative stress and Copper entries.Cohort excluded tesamorelin; recombinant GH (H01AC01), not a GHRH analog. Used only as class-level mechanistic context, clearly labeled as such in both entries.
  13. Richards GE, Marshall RN. Relationship between zinc and growth hormone (GH) in GH deficient children. — Prospective observational study, n=8 children with GH deficiency, pituitary-derived GH (NOT tesamorelin), up to two years. No significant change in serum, urine, or hair zinc with GH treatment. Used as brief supporting context in the Copper entry's counter-evidence, not as its own graded entry.Cohort excluded tesamorelin; pituitary-derived GH, a different drug in the same broad axis, not the same ATC-class agent used for the Copper/Oxidative stress entries' primary citation.
  14. Yu Z, Wang Y, Zhang F, et al. Deletion of hepatic growth hormone receptor (GHR) alters the mouse gut microbiota by affecting bile acid metabolism. — Mouse hepatic/adipose GHR-knockout model (loss of GH signaling), not exogenous GH or GHRH-analog administration. Source for the Gut microbiome risk entry.
  15. Crosstalk between the growth hormone/insulin-like growth factor-1 axis and the gut microbiome: a new frontier for microbial endocrinology. — Reviewed for tesamorelin/GHRH-analog-specific content; confirmed the review relies entirely on genetic knockout/transgenic mouse models (GH-/-, bGH-transgenic, IntGHRKO), not pharmacological GH or GHRH-analog administration, and does not mention tesamorelin. Used only to confirm the absence of a stronger mechanistic lead, not cited as direct support for any grade.
  16. ScienceDirect Topics. Tesamorelin, pharmacology overview. — Tertiary reference used to cross-check general pharmacology and clinical-use framing; contains no electrolyte, mineral, oxidative-stress, or mitochondrial content of its own.
  17. Mayo Clinic. Tesamorelin (subcutaneous route), side effects and dosage. — Consumer reference used for the circulating-claim audit; no vitamin, mineral, or microbiome claims found.
  18. Swolverine. Tesamorelin Peptide Guide: Fat Loss, Benefits, Dosage, Side Effects. — Peptide/fitness-marketing reference used for the circulating-claim audit; no nutrient, mineral, mitochondrial, or microbiome claims found.
  19. Innerbody. Tesamorelin Peptide: Benefits, Safety, and Buying Advice. — Consumer/peptide-marketing reference used for the circulating-claim audit; no nutrient, mineral, mitochondrial, or microbiome claims found.
  20. Vihervuori E, Cook JD, Siimes MA. Iron status of children with short stature during accelerated growth due to growth hormone treatment. — Prospective observational study, n=35 children with short stature, 6 months of recombinant GH (NOT tesamorelin). Cohort-tested and confirmed as a class-extrapolation (Tier C) source for the Iron entry. Abstract reconstructed and read via the OpenAlex API's single-record DOI lookup (its abstract_inverted_index) this session; the Wiley Online Library article page itself returned an HTTP 403 error on direct fetch, so only the abstract, not the full paper, was opened.Cohort excluded tesamorelin; recombinant GH (H01AC01), not a GHRH analog. Used only as class-level mechanistic context, clearly labeled as such in the Iron entry. Full paper not opened; abstract only, retrieved via OpenAlex.
  21. Miniero R, Altomare F, Rubino M, Matarazzo P, Montanari C, Petri A, Raiola G, Bona G. Effect of Recombinant Human Growth Hormone (rhGH) on Hemoglobin Concentration in Children With Idiopathic Growth Hormone Deficiency-related Anemia. — Retrospective multicenter study, n=279 children with isolated idiopathic GH deficiency (48 anemic at baseline), rhGH therapy (NOT tesamorelin), followed up to 48 months. Cohort-tested and confirmed as a class-extrapolation (Tier C) source for the Oxygen delivery/utilization entry. Abstract reconstructed and read via the OpenAlex API's single-record DOI lookup (its abstract_inverted_index) this session; the individual PubMed abstract page returned only an automated bot-verification/metadata skeleton, and journals.lww.com returned an HTTP 402 paywall error, so only the abstract, not the full paper, was opened.Cohort excluded tesamorelin; recombinant GH, a different drug in the same broad axis, not a GHRH analog. Used only as class-level mechanistic context, clearly labeled as such in the Oxygen delivery/utilization entry. Full paper not opened; abstract only, retrieved via OpenAlex.