Aggregated evidence base

Zhu D. et al.

McGuire FP, Martinez R, Lenz A, Skinner L, Cushman DM

Findings:Confirms the large gap between how widely it is used and the robust human evidence available.

Limitations:Narrative (not systematic) review; summarises predominantly preclinical work.

Wang Y. et al.

Findings:Dose-dependent weight reduction versus placebo; high completion (93%). GI effects most common.

Limitations:China-only, non-diabetic population; limited generalisability; long-term cardiovascular outcomes pending.

Ji L. et al.

Wu J, et al.

Findings:No difference: 23.4% vs. 24.1% mortality (HR 0.99; P=0.93). No secondary or safety endpoint was significant. Subgroup signals (age, diabetes) are hypothesis-generating only.

Limitations:Primary endpoint missed; subgroup analyses exploratory; single-country (China).

European Medicines Agency

Zhu D. et al.

Findings:Mean weight loss about 9.0–9.6% versus minimal change on placebo; HbA1c improved.

Limitations:Phase 2, China, type 2 diabetes; shorter duration.

Thompson WR, Hornby B, Reid Thompson W, et al.

European Medicines Agency

European Commission DG GROW

Zhang B. et al.

U.S. FDA

European Medicines Agency / U.S. FDA

Sanyal AJ. et al.

Eli Lilly and Company / ClinicalTrials.gov

European Commission DG GROW

Le Roux CW. et al.

Sanyal AJ. et al.

Findings:MASH improvement occurred in 47–62% depending on dose vs. 14% on placebo; fibrosis improvement by at least one stage in 34–36% vs. 22%.

Limitations:Phase 2, 48 weeks, histological surrogate endpoints; long-term clinical outcomes and phase 3 confirmation pending (SYNCHRONIZE program).

Findings:Dose-dependent weight reduction of up to about 12% versus placebo; in the highest-dose group 55% of participants achieved at least 15% weight loss. Gastrointestinal effects were most common.

Limitations:Phase 2, dose-finding, 46 weeks; non-diabetic; cardiovascular/long-term outcomes pending in phase 3 (SYNCHRONIZE).

European Medicines Agency

U.S. Food and Drug Administration

Findings:Rationale includes lack of characterised safety, purity and identity in available sources.

Frias JP. et al.

Ziganshina LE, Abakumova T, Nurkhametova D, Ivanchenko K

Romero-Gómez M. et al.

Karaa A, Bertini E, Carelli V, et al.

Jastreboff AM, Kaplan LM, Frías JP. et al.

Mills EG. et al.

Ji L. et al.

Jastreboff AM. et al.

Rosenstock J. et al.

Lincoff AM et al.

Findings:Statistically significant reduction of the primary cardiovascular endpoint.

Garvey WT, et al.

Findings:Mean weight loss 13.4% (10 mg) and 15.7% (15 mg) vs. 3.3% on placebo; 79–83% reached ≥5% weight loss vs. 32%.

Limitations:Even with diabetes, weight loss is usually somewhat lower than in people without diabetes; GI effects were the most common adverse events.

Atiq F. et al.

Alser M, et al.

Ji L. et al.

Alser M, et al.

Coskun T. et al.

Haqq AM. et al.

Jastreboff AM. et al.

Findings:Substantial weight reduction versus placebo was reported in the treatment arm.

Enebo LB. et al.

Lau DCW. et al.

Kruse T, Hansen MK, Petersen A, Andersen B. (Novo Nordisk research)

Frias JP. et al.

Alba M. et al.

Di Prospero NA. et al.

Reid Thompson W, Hornby B, Manuel R, et al.

Reynolds JC, Lai RW, Woodhead JST, et al.

Findings:MOTS-c is induced by exercise; in animal models it improved physical capacity and countered age-related muscle decline. In humans it rises in muscle/blood after exertion.

Limitations:Efficacy evidence predominantly animal; human data so far observational (expression), not interventional.

Wilding JPH et al.

Findings:Clinically meaningful weight loss vs. placebo with concurrent lifestyle intervention.

Limitations:Limited observation period; weight regain after discontinuation documented in follow-up publications.

Markham A.

Hauser B et al.

Wong F, et al.

Findings:Higher rate of HRS reversal with terlipressin+albumin than placebo+albumin; respiratory complications as a safety signal.

Limitations:High disease severity; respiratory-failure risk requires careful patient selection.

Rosenstock J. et al.

Findings:Significant HbA1c reduction was reported in the treatment arm versus placebo.

Frías JP. et al.

Cosman F, Peterson LR, Towler DA, et al.

Wensink D., Wagenmakers MAEM., Barman-Aksözen J. et al.

Poon W, Matula C, Vos PE, Muresanu DF, et al.

Butler J, Khan MS, Anker SD, et al.

U.S. FDA

Kirkland JL., Tchkonia T.

Peters B, Hadimeri H, Wahlberg R, Afghahi H

Findings:Extends the documented spectrum of serious vascular events beyond the cardiovascular effects.

Limitations:Single case; causality not proven; grey-market product not analysed.

Yamasue H. et al.

Clément K. et al.

Kuznik BI. et al.

Leder BZ, Zapalowski C, Hu MY, et al.

Kingsberg SA. et al.

U.S. FDA

Cui S, Chen N, Yang M, Guo J, Zhou M, Zhu C, He L

Gerstein HC. et al.

Zhang L, Cai K, Wang Y, Ji W, Cheng Z, Chen G, Liao Z

Stanley TL. et al.

Stanley TL, et al.

Findings:Tesamorelin reduced hepatic fat fraction by about 37% relative to placebo and prevented fibrosis progression over one year.

Limitations:Small sample (n=61), HIV population; not transferable to the general fatty-liver population.

Bornstein NM, Guekht A, Vester J, Heiss WD, et al.

Tuttle KR. et al.

Pickart L, Margolina A.

Findings:Review of GHK-Cu: gene modulation, wound healing, antioxidant/anti-inflammatory effects — predominantly preclinical and cell data.

Limitations:Narrative review; the robust human evidence is limited to topical cosmetics.

Yen K, Wan J, Mehta HH, et al.

Comninos AN. et al.

Kendler DL et al.

Shirley M

Hsieh MJ et al.

Findings:BPC-157 modulated VEGF signalling and endothelial migration patterns in cell culture.

Limitations:In-vitro finding; says nothing about in-vivo efficacy or clinical relevance.

Holman RR. et al.

Baar MP. et al.

Le Bras A.

Yale JF, Dulude H, Egeth M. et al.

Comninos AN. et al.

Xiao B et al.

Findings:The carrier system was associated with accelerated mucosal healing and reduced inflammation in the model.

Limitations:Animal model with a specific formulation approach; no human data and no statement on clinical use.

Danne T. et al.

Habbema L., Halk AB., Neumann M., Bergman W.

U.S. Food and Drug Administration

Findings:Thyroid C-cell tumours in rats under GLP-1 analogues; human relevance not established.

Lebret T. et al.

Miller PD, Hattersley G, Riis BJ, et al.

Clayton AH. et al.

Wells G et al.

Rickels MR, Ruedy KJ, Foster NC. et al.

Viennois E et al.

Findings:PepT1 is discussed as a possible therapeutic target; KPV showed anti-inflammatory effects in the model.

Limitations:Animal model; mechanistic conclusions are not readily transferable to humans.

Marso SP. et al.

Marso SP et al.

Findings:Reduction of composite cardiovascular endpoints vs. placebo in high-risk patients.

Kühnen P. et al.

Langendonk JG. et al.

Minder EI., Barman-Aksözen J.

Biolcati G. et al.

Lim SH., Sun Y., Madanagopal TT., Rosa V., Kang L.

Mendell J.R., Sahenk Z., Malik V., et al.

Pickart L et al.

Findings:Compilation of preclinical findings on gene expression, wound healing, antioxidation.

Limitations:Review format; selection bias possible.

Moore HCF et al.

Jayasena CN. et al.

Pi-Sunyer X. et al.

Pfeffer MA. et al.

Lee C, Zeng J, Drew BG, et al.

Sosne G et al.

Australian Therapeutic Goods Administration

Albertsen PC et al.

Wysham C. et al.

Khavinson VKh., Linkova NS., Tarnovskaya SI.

Beck DE. et al.

Caplin ME, Pavel M, Ćwikła JB, et al.

Findings:Lanreotide significantly prolonged progression-free survival versus placebo.

Limitations:Narrowly defined tumour population; an overall-survival benefit was not primarily shown in this trial.

Philippou A., Barton ER.

Caplin ME. et al.

Khavinson VKh., Linkova NS., Tarnovskaya SI.

Wang Y. et al.

Rosenstock J. et al.

Riddle MC. et al.

Devlin J, Pomerleau A, Foote J

Findings:Documented urological complication after overdose — consistent with the erectogenic melanocortin effect.

Limitations:Single case, very short publication; no frequency conclusion.

Medvedev VE. et al.

Wu J. et al.

Damber JE et al.

Lee PA et al.

Fonseca VA. et al.

Dombrowski Y. et al.

Nelson ME, Bryant SM, Aks SE

Findings:Severe systemic toxicity after grey-market sourcing; the report describes full recovery.

Limitations:Single case (n=1), no proof of causality; purity/content of the internet product unknown.

Sivyer GW

Findings:Melanocytic lesions visibly changed during use — particularly relevant in genetic melanoma risk.

Limitations:Single case; concurrent UV use as confounder; no general frequency conclusion derivable.

Anagnostou E. et al.

Colao A, et al. (Pasireotide B2305 Study Group)

Findings:Pasireotide lowered urinary free cortisol in a relevant proportion of patients; hyperglycemia was a frequent issue.

Limitations:Hyperglycemia/diabetes as a class-limiting effect (SSTR5-mediated).

Jeppesen PB, et al.

Findings:Clinically meaningful response in 63% on teduglutide vs. 30% on placebo.

Limitations:Rare disease, limited sample; the trophic effect requires long-term monitoring.

Chang CH et al.

Findings:Treated animals showed improved healing parameters versus control.

Limitations:Animal model, small sample, no long-term follow-up. Not transferable to humans without clinical studies.

Yuen KCJ.

Lumry WR, et al.

Findings:Icatibant markedly shortened median time to symptom relief versus placebo (2.0 vs. 19.8 h).

Limitations:Acute endpoints; rare disease.

Jeppesen PB, et al.

Findings:Early randomized trial showing the benefit of teduglutide in reducing parenteral requirements.

Ng FM. et al.

Sikiric P et al.

Findings:Aggregates several animal studies on gastric mucosal protection, ulcer healing and gastrointestinal adaptations.

Limitations:Review by the same research group — possible selection bias. No human data.

Tombal B et al.

Lee S.J., Lee Y.S., Zimmers T.A., et al.

Shadrina MI. et al.

Sosne G et al.

Satterwhite J et al.

Findings:Carbetocin effectively and practically prevents postpartum hemorrhage as a single dose.

Buse JB. et al.

Muzumdar RH, Huffman DM, Atzmon G, et al.

Garber A. et al.

Trookman NS. et al.

Lintner K.

Langan EA. et al.

Rinke A. et al.

Alfirevic Z., Kelly AJ., Dowswell T.

Carel JC. et al.

Klotz L et al.

Nakatani M., Takehara Y., Sugino H., et al.

Dalmasso G et al.

Findings:Uptake via PepT1; reduced pro-inflammatory cytokine expression in vitro and histologically lower inflammation in DSS- and TNBS-colitis.

Limitations:Cell lines and animal model; no human data. Model colitis is only partially transferable to humans.

Kannengiesser K et al.

Findings:KPV treatment showed anti-inflammatory effects versus untreated controls in the models examined.

Limitations:Animal model only, small samples; not transferable to humans without clinical studies.

Zozulia AA. et al.

Uchakina ON. et al.

U.S. Food and Drug Administration

Findings:Withdrawal was commercially motivated, not driven by safety findings by the regulator.

Lipotec S.A.

Kaufmann M et al.

Mills P. et al.

Falutz J. et al.

Falutz J, et al.

Findings:Visceral fat fell by about 15% (vs. a ~5% rise on placebo); IGF-1 increased and lipids improved, without relevant glucose worsening.

Limitations:Narrowly defined indication (HIV lipodystrophy); 26 weeks; not transferable to general 'fat-loss' use.

Diamond LE. et al.

Teichman SL et al.

Findings:Sustained elevation of GH and IGF-1 over several days.

Limitations:Small sample, short observation, surrogate-oriented endpoints.

Ionescu M, Frohman LA

Findings:GH pulses were preserved over the observation period, with elevated baseline.

Limitations:Very small sample, no clinical endpoints recorded.

Alba M. et al.

Findings:Growth normalisation in the animal model; evidence for functional activity of the DAC modification.

Limitations:Animal model — translation to adults with intact GH axis is not direct.

Findings:Despite continuous CJC-1295 stimulation, pulsatile GH secretion persisted; GH pulse amplitude rose while pulse frequency was unchanged.

Limitations:Mechanistic early-phase study, no clinical outcomes.

Korkushko OV. et al.

Dürr UHN. et al.

Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA

Knopp JA et al.

Kendall DM. et al.

Laferrère B. et al.

Tokumaru S. et al.

Robinson LR. et al.

Kosfeld M., Heinrichs M., Zak PJ., Fischbacher U., Fehr E.

Gusev EI. et al.

Findings:Complete response 42.3% vs. 3.3% in controls; among responders, HBV DNA remained undetectable in 83.3% even 6 months after treatment.

Limitations:Limited sample size; hepatitis-B-specific; older study.

Rosen RC. et al.

Bock-Marquette I et al.

Lalezari JP, et al.

Findings:Adding enfuvirtide to optimised background therapy lowered viral load markedly more than background therapy alone.

Limitations:Treatment-experienced population; twice-daily injection.

Khavinson VKh. et al.

Torsello A. et al.

Heilborn JD. et al.

Hill M., Goldspink G.

Philp D et al.

Khavinson VKh.

Philp D et al.

Heyns CF. et al.

Blanes-Mira C. et al.

Blanes-Mira C, et al.

Findings:Forehead wrinkle depth fell by up to 30% versus vehicle in the pilot; cell models showed dose-dependent inhibition of catecholamine exocytosis (SNARE mechanism).

Limitations:Very small, uncontrolled topical pilot (n=10); foundational work, not a large RCT.

Dunn AL. et al.

Findings:Ovarian stimulation with ganirelix was unremarkable/safe regarding pregnancy and neonatal outcomes.

Leyden JJ et al.

Findings:Statistical improvement in several skin parameters versus control.

Limitations:Cosmetic study with manufacturer involvement; partly subjective endpoints; no long-term data.

Leyden J, et al.

Findings:Increased skin density and thickness, improved firmness and clarity, reduced fine lines and wrinkle depth (ultrasound/profilometry).

Limitations:Cosmetic study of TOPICAL use — not transferable to injected/systemic use.

Broglio F. et al.

Yang S. et al.

Kaplan AYa., Kochetova AG., Nezavibathko VN. et al.

Blanes-Mira C. et al.

Khavinson VKh. et al.

Anisimov VN. et al.

Lee S.J., McPherron A.C.

Hashimoto Y, Niikura T, Tajima H, et al.

Prelle K, et al.

Kost NV., Sokolov OYu., Zolotarev YuA., Andreeva LA. et al.

Neer RM et al.

Chien RN. et al.

Ng FM. et al.

Chesnut CH 3rd et al.

Cockshott ID

Svensson J. et al.

Knudsen LB. et al.

Kojima M. et al.

Gobburu JV. et al.

Ling FW (Pelvic Pain Study Group)

Prakash A, Goa KL

Mericq V. et al.

Büchter D, Behre HM, Kliesch S, Nieschlag E

Raun K. et al.

Wessells H. et al.

Skoog SJ. et al.

Pihoker C. et al.

Ashmarin IP. et al.

Thorner MO et al.

Findings:GHRH analogues induce a physiological, pulsatile GH response at the pituitary.

Malinda KM et al.

Malinda KM et al.

Howard AD. et al.

Tomas FM, et al.

Dorr RT. et al.

Lamberts SW. et al.

Ghigo E. et al.

Laron Z. et al.

Conlon MA, et al.

Bajetta E et al.

Ghigo E. et al.

Imbimbo BP. et al.

Kirk JM, Trainer PJ, Majrowski WH, Murphy J, Savage MO, Besser GM

Katayama K. et al.

Wilton P, Chardet Y, Danielson K, Widlund L, Gunnarsson R

Eng J. et al.

Bowers CY. et al.

Singer FR et al.

Bowers CY. et al.

The Medical Letter on Drugs and Therapeutics

Dlugi AM et al.

Crawford ED et al.

Maquart FX et al.

Findings:Dose-dependent increase in collagen markers in cell culture.

Limitations:In-vitro finding without predictive value for intact human skin.

Guler HP, et al.

Stick SM, Betts PR.

Schneider-Helmert D, Schoenenberger GA

Graf MV, Kastin AJ

Thorner MO. et al.

Graf MV, Kastin AJ

Hurley DM, Brian R, Outch K, Stockdale J, Fry A, Hackman C, Clarke I, Burger HG

Bauer W. et al.

Guillemin R., Brazeau P., Böhlen P., Esch F., Ling N., Wehrenberg WB.

Schoenenberger GA, Monnier M