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Unanswered questions

Questions with no answer at all. Not questions with no accepted answer — those are elsewhere.

741 questions · page 26 of 31

37 votes0 answers19k views
Can I reconstitute cagrilintide at 4 mg/mL and still measure a small dose accurately?

Numbers first: cagrilintide · 4 mg/mL. This is a planning question. I know what my options are; I do not know how to weigh them. What I want is the minimum viable…

diluent-volume
diluent-volume

Choosing how much diluent to add, which is really a question about what you want your measurement resolution to be. Larger volumes buy you…

308 questions
insulin-syringe
insulin-syringe

U-100 and U-40 insulin syringes as measuring instruments. A U-100 syringe is graduated in insulin units where 100 units equals 1 mL, so one unit…

268 questions
dosing-math
dosing-math

The arithmetic itself: milligrams to millilitres to insulin units, concentration after reconstitution, dose per draw, and vial-days per vial. Show…

811 questions
asked by bridget_nyathi 16k · 23 months ago
21 votes0 answers27k views
What does REDEFINE-1 actually establish about survodutide?

The specifics, since they change the answer: REDEFINE-1 · survodutide. I want to understand what this actually establishes, as opposed to what it is being used to…

clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
semaglutide
semaglutide

A GLP-1 receptor agonist with a fatty-acid-acylated backbone and a roughly one-week half-life, marketed for type 2 diabetes and for weight…

360 questions
cardiovascular
cardiovascular

Cardiovascular outcomes: the SELECT major-adverse-event result, SOUL, SUSTAIN 6 and REWIND, how to convert a hazard ratio into an absolute risk…

111 questions
asked by deamidation_watch 43k · 23 months ago
9 votes0 answers14k views
Does splitting a 50 mg weekly dose of survodutide across two administrations change anything?

For reference: 50 mg · survodutide. I would like the mechanism, because I want to be able to reason about the cases nobody has written about. I have tried to reason…

split-dosing
split-dosing

Dividing a weekly dose across more than one administration. Questions here concern the pharmacokinetic rationale, whether the peak-to-trough ratio…

39 questions
dosing-math
dosing-math

The arithmetic itself: milligrams to millilitres to insulin units, concentration after reconstitution, dose per draw, and vial-days per vial. Show…

811 questions
glp1-mechanism
glp1-mechanism

Receptor-level pharmacology: GLP-1R as a class B GPCR, cAMP and PKA signalling, biased agonism, internalisation and resensitisation, and the…

175 questions
mazdutide
mazdutide

A GLP-1 and glucagon receptor dual agonist developed primarily in China, with a distinct dose range and a fast-moving publication record.…

14 questions
asked by Dr_Fatima_Belkacem 52k · 23 months ago
37 votes0 answers18k views
Does fibrillation of semaglutide at 30 °C show up as a loss of content or of purity?

The particulars: fibrillation · semaglutide · 30 °C. I would like the mechanism, because I want to be able to reason about the cases nobody has written about. I have…

peptide-stability
peptide-stability

The chemistry of peptide degradation: deamidation, oxidation, hydrolysis, aggregation and fibrillation, and how temperature, pH, ionic strength,…

832 questions
content-assay
content-assay

Quantified content: how many milligrams of peptide are actually in the vial, measured against a calibrated reference standard. A separate test…

438 questions
purity
purity

Purity as chromatographic area per cent - the fraction of detected material that is your target peak. It says nothing about how much material is…

788 questions
asked by g_paskevicius 44k · 23 months ago
8 votes0 answers5.5k views
What is the arithmetic to convert 5 mg in 3 mL into units on a U-100 scale?

What I am working with: 5 mg · 3 mL. I have worked this out and I would like someone to find the error, because I suspect there is one. My working so far, for the…

dosing-math
dosing-math

The arithmetic itself: milligrams to millilitres to insulin units, concentration after reconstitution, dose per draw, and vial-days per vial. Show…

811 questions
insulin-syringe
insulin-syringe

U-100 and U-40 insulin syringes as measuring instruments. A U-100 syringe is graduated in insulin units where 100 units equals 1 mL, so one unit…

268 questions
reconstitution
reconstitution

Taking a lyophilised vial to a solution of known concentration: choice of diluent, volume selection, how to add liquid without shearing the cake,…

330 questions
asked by rune_thoresen 14k · 23 months ago
34 votes0 answers37k views
Is ALT a better monitoring choice than AST on semaglutide?

Stated plainly: ALT · AST · semaglutide. Both of these get recommended confidently by different people, which suggests neither is obviously right. My constraints are…

bloodwork
bloodwork

Laboratory monitoring: which panels are worth ordering, sensible intervals, reference-range versus optimal-range arguments, and how to read a…

284 questions
kidney-function
kidney-function

eGFR, creatinine, cystatin C and albuminuria: the acute haemodynamic dip that is not injury, the renal outcome data from the FLOW programme, and…

100 questions
lipids
lipids

Lipid response on treatment: triglycerides, LDL-C, non-HDL-C, ApoB and Lp(a), which of them move with weight loss, and why a fasting panel drawn…

112 questions
asked by Dr_Marek_Zielinski 39k · 23 months ago
9 votes0 answers5.9k views
Is fatigue on dulaglutide dose-dependent or dose-rate dependent?

Numbers first: fatigue · dulaglutide. I suspect the usual explanation for this is wrong, or at least incomplete. I am aware this may have a boring answer. I would…

nausea
nausea

The dominant tolerability signal in every trial of the class: incidence, timing relative to a dose step, duration, and the distinction between…

346 questions
titration
titration

Stepwise dose increases over weeks, why the label schedules exist at all, and what tolerability-driven deviation from a schedule looks like in…

444 questions
gi-side-effects
gi-side-effects

The gastrointestinal cluster as a whole - nausea, vomiting, diarrhoea, constipation, reflux, early satiety - with trial incidence rates, dropout…

416 questions
asked by b_delacroix 48k · 23 months ago
27 votes0 answers27k views
How should I budget for a Karl Fischer water content test across a twelve-month oral semaglutide course?

The case in front of me: a Karl Fischer water content test · oral semaglutide. I want to decide this in advance so that I am not deciding it under pressure later.…

batch-testing
batch-testing

Testing at the batch or lot level: sampling plans, how many vials from a lot need testing to say anything about the lot, and the difference…

865 questions
cost-analysis
cost-analysis

Cost arithmetic done honestly: cost per milligram after dead-space loss, list versus net price, comparing a multi-dose vial to a fixed-dose pen,…

261 questions
janoshik
janoshik

Janoshik Analytical, an independent third-party testing laboratory widely used by this community for HPLC purity, identity and quantified content…

34 questions
asked by triple_agonist_q 37k · 23 months ago
17 votes0 answers18k views
Is liraglutide at 1 mg/mL stable enough for twelve weeks of multi-withdrawal use?

The particulars: liraglutide · 1 mg/mL · twelve weeks. I would like to know whether this claim survives contact with evidence. If the answer is "nobody has tested…

peptide-stability
peptide-stability

The chemistry of peptide degradation: deamidation, oxidation, hydrolysis, aggregation and fibrillation, and how temperature, pH, ionic strength,…

832 questions
bacteriostatic-water
bacteriostatic-water

Water for injection containing roughly 0.9 per cent benzyl alcohol as a bacteriostatic agent. It suppresses growth in a multiple-withdrawal vial;…

112 questions
shelf-life
shelf-life

How long a preparation remains within specification: labelled expiry for a sealed lyophilised vial, beyond-use dating after reconstitution, and…

301 questions
asked by sample_id 17k · 23 months ago
26 votes0 answers18k views
How many units on a U-100 insulin syringe is a 5 mg dose at 2 mg/mL?

The particulars: a U-100 insulin syringe · 5 mg · 2 mg/mL. I would like the arithmetic checked rather than the conclusion asserted. I have deliberately not used an…

dosing-math
dosing-math

The arithmetic itself: milligrams to millilitres to insulin units, concentration after reconstitution, dose per draw, and vial-days per vial. Show…

811 questions
insulin-syringe
insulin-syringe

U-100 and U-40 insulin syringes as measuring instruments. A U-100 syringe is graduated in insulin units where 100 units equals 1 mL, so one unit…

268 questions
reconstitution
reconstitution

Taking a lyophilised vial to a solution of known concentration: choice of diluent, volume selection, how to add liquid without shearing the cake,…

330 questions
asked by mira_sundqvist 19k · 23 months ago
38 votes0 answers29k views
How comparable are dulaglutide and semaglutide on the evidence available?

Stated plainly: dulaglutide · semaglutide. I suspect the honest answer is that it depends, in which case I would like to know on what. Assume I can obtain either…

clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
semaglutide
semaglutide

A GLP-1 receptor agonist with a fatty-acid-acylated backbone and a roughly one-week half-life, marketed for type 2 diabetes and for weight…

360 questions
tirzepatide
tirzepatide

A dual GIP and GLP-1 receptor agonist. Questions here cover the SURPASS and SURMOUNT programmes, the practical differences from a pure GLP-1…

162 questions
asked by bufferline42 49k · 23 months ago
18 votes0 answers24k views
What should be in place before a first dulaglutide vial arrives from Wuxi?

Setup, so nobody has to ask: dulaglutide · Wuxi. I am trying to build something sustainable rather than something thorough that I will abandon. I have already decided…

harm-reduction
harm-reduction

Reducing avoidable risk where a decision has already been made: independent verification before use, sterility practice, dose arithmetic checked…

445 questions
research-use-only
research-use-only

What "for research use only" means as a legal and practical designation: not approved for human use, no pharmacopoeial release testing, no…

91 questions
sterility
sterility

Sterility as a test result rather than an adjective. Covers what a sterility test actually measures, why "sterile filtered" on a document is close…

122 questions
asked by pip_okonjo 11k · 23 months ago
31 votes0 answers42k views
Why does aspartimide formation accelerate at 30 °C rather than proceeding linearly?

Concretely: aspartimide formation · 30 °C. I want to know whether this is a real physical effect or an artefact of how it is measured. What prompted the question is…

peptide-stability
peptide-stability

The chemistry of peptide degradation: deamidation, oxidation, hydrolysis, aggregation and fibrillation, and how temperature, pH, ionic strength,…

832 questions
storage
storage

Storage conditions and their evidence base: minus twenty degrees for powder, refrigerated for solution, protection from light, and what the…

646 questions
hplc
hplc

Reverse-phase high-performance liquid chromatography, the workhorse purity method. Column chemistry, mobile-phase choice, gradient slope,…

466 questions
asked by thabo_maseko 20k · 2.0 years ago
27 votes0 answers18k views
Is 10 mg weekly a defensible maintenance dose for tirzepatide?

Conditions: 10 mg · tirzepatide. The failure mode I am trying to avoid is making this decision emotionally. I have twelve months in view and I would like the plan to…

maintenance-dose
maintenance-dose

Staying put: the lowest dose that holds a result, the difference between the maximum studied dose and the maximum useful dose, and what the…

44 questions
clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
dosing-math
dosing-math

The arithmetic itself: milligrams to millilitres to insulin units, concentration after reconstitution, dose per draw, and vial-days per vial. Show…

811 questions
asked by ines_delacruz 16k · 2.0 years ago
15 votes0 answers13k views
How does retatrutide at 4 mg weekly compare on cost per milligram across routes?

What I am working with: retatrutide · 4 mg. I have worked this out and I would like someone to find the error, because I suspect there is one. My working so far, for…

cost-analysis
cost-analysis

Cost arithmetic done honestly: cost per milligram after dead-space loss, list versus net price, comparing a multi-dose vial to a fixed-dose pen,…

261 questions
vendor-comparison
vendor-comparison

Side-by-side comparison of suppliers on measurable axes - independently confirmed purity and content, lead time, cold-chain handling,…

351 questions
dosing-math
dosing-math

The arithmetic itself: milligrams to millilitres to insulin units, concentration after reconstitution, dose per draw, and vial-days per vial. Show…

811 questions
asked by noor_alhassan 15k · 2.0 years ago
29 votes0 answers12k views
Is hair thinning on mazdutide dose-dependent or dose-rate dependent?

Setup, so nobody has to ask: hair thinning · mazdutide. I keep seeing this stated as a fact with no explanation attached, and unexplained facts make me suspicious. My…

nausea
nausea

The dominant tolerability signal in every trial of the class: incidence, timing relative to a dose step, duration, and the distinction between…

346 questions
titration
titration

Stepwise dose increases over weeks, why the label schedules exist at all, and what tolerability-driven deviation from a schedule looks like in…

444 questions
gi-side-effects
gi-side-effects

The gastrointestinal cluster as a whole - nausea, vomiting, diarrhoea, constipation, reflux, early satiety - with trial incidence rates, dropout…

416 questions
asked by Dr_Bram_Verhoeven 85k · 2.0 years ago
27 votes0 answers36k views
What does the mechanism of retatrutide predict that SURMOUNT-4 did not test?

Stated plainly: retatrutide · SURMOUNT-4. I keep seeing this stated as a fact with no explanation attached, and unexplained facts make me suspicious. My background is…

glp1-mechanism
glp1-mechanism

Receptor-level pharmacology: GLP-1R as a class B GPCR, cAMP and PKA signalling, biased agonism, internalisation and resensitisation, and the…

175 questions
clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
gip-receptor
gip-receptor

GIP receptor pharmacology, and the still-unsettled question of whether agonism or antagonism at GIPR is the metabolically useful direction.…

83 questions
asked by cake_collapsed 13k · 2.0 years ago
30 votes0 answers31k views
Is a 98.2% result from Janoshik comparable to 96.8% from Medutest?

What I have: 98.2% · Janoshik · 96.8% · Medutest. I have used one of these for a while and I am considering switching, which requires a reason. What I care about is…

purity
purity

Purity as chromatographic area per cent - the fraction of detected material that is your target peak. It says nothing about how much material is…

788 questions
batch-testing
batch-testing

Testing at the batch or lot level: sampling plans, how many vials from a lot need testing to say anything about the lot, and the difference…

865 questions
reference-standard
reference-standard

Certified reference materials and in-house standards: traceability, the certificate of the standard itself, system suitability, and why every…

179 questions
asked by Dr_Ravi_Selvarajah 42k · 2.0 years ago
34 votes0 answers13k views
How does QST compare to Zhuhai Kerui Biotechnology on documentation quality?

Conditions: QST · Zhuhai Kerui Biotechnology. These are treated as interchangeable and I do not think they are. If both are acceptable I would like to know that, so I…

vendor-comparison
vendor-comparison

Side-by-side comparison of suppliers on measurable axes - independently confirmed purity and content, lead time, cold-chain handling,…

351 questions
coa
coa

Certificates of analysis: what fields a useful one carries, how to tell a real analytical report from a marketing document, batch and lot…

749 questions
vendor-vetting
vendor-vetting

Evaluating a supplier on evidence rather than reputation: testing history across batches, whether certificates are batch-specific, how failures…

436 questions
asked by anja_hellstrom 13k · 2.0 years ago
27 votes0 answers29k views
What did REDEFINE-1 do with participants who could not tolerate a step?

The label documentation for the agent in question is ambiguous on exactly this point. The figures are clear enough; the question is what they mean and what they do…

titration
titration

Stepwise dose increases over weeks, why the label schedules exist at all, and what tolerability-driven deviation from a schedule looks like in…

444 questions
clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
gi-side-effects
gi-side-effects

The gastrointestinal cluster as a whole - nausea, vomiting, diarrhoea, constipation, reflux, early satiety - with trial incidence rates, dropout…

416 questions
asked by fresh_bac 13k · 2.0 years ago
17 votes0 answers13k views
Does the SURMOUNT-OSA result mean CPAP can be stopped?

I have the full paper rather than the abstract, and the supplementary appendix. I am at the decision point and I would rather think it through than improvise. I would…

sleep-apnea
sleep-apnea

Obstructive sleep apnoea and the apnoea-hypopnoea index response to weight loss, including the SURMOUNT-OSA dataset and the question of whether…

14 questions
clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
cardiovascular
cardiovascular

Cardiovascular outcomes: the SELECT major-adverse-event result, SOUL, SUSTAIN 6 and REWIND, how to convert a hazard ratio into an absolute risk…

111 questions
asked by Dr_Idris_Coulibaly 40k · 2.0 years ago
2 votes0 answers1.9k views
What is the reported incidence of constipation on oral semaglutide in SUSTAIN-6?

Concretely: constipation · oral semaglutide · SUSTAIN-6. I would like to know the limits of what can be inferred from this. What I am trying to avoid is over-reading…

gi-side-effects
gi-side-effects

The gastrointestinal cluster as a whole - nausea, vomiting, diarrhoea, constipation, reflux, early satiety - with trial incidence rates, dropout…

416 questions
clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
nausea
nausea

The dominant tolerability signal in every trial of the class: incidence, timing relative to a dose step, duration, and the distinction between…

346 questions
asked by kelvin_lam 11k · 2.0 years ago
37 votes0 answers26k views
Why did two MKM lots of survodutide differ on content assay?

The specifics, since they change the answer: MKM · survodutide. An unexpected observation, and I would like a differential rather than reassurance. The conditions…

batch-testing
batch-testing

Testing at the batch or lot level: sampling plans, how many vials from a lot need testing to say anything about the lot, and the difference…

865 questions
content-assay
content-assay

Quantified content: how many milligrams of peptide are actually in the vial, measured against a calibrated reference standard. A separate test…

438 questions
vendor-vetting
vendor-vetting

Evaluating a supplier on evidence rather than reputation: testing history across batches, whether certificates are batch-specific, how failures…

436 questions
asked by rukhsana_iqbal 14k · 2.0 years ago
9 votes0 answers13k views
Has anyone independently verified a JEEP retatrutide batch COA?

Details up front: JEEP · retatrutide. I would rather be corrected now than propagate something wrong. I am specifically not interested in a testimonial; I am…

vendor-vetting
vendor-vetting

Evaluating a supplier on evidence rather than reputation: testing history across batches, whether certificates are batch-specific, how failures…

436 questions
coa
coa

Certificates of analysis: what fields a useful one carries, how to tell a real analytical report from a marketing document, batch and lot…

749 questions
batch-testing
batch-testing

Testing at the batch or lot level: sampling plans, how many vials from a lot need testing to say anything about the lot, and the difference…

865 questions
asked by Dr_Tomas_Kral 37k · 2.0 years ago