This page shows what was measured, who it was measured in, and what that does not settle.
What Insulin degludec does in the body
Insulin normally has to be released slowly and steadily to keep the liver from dumping sugar into the blood overnight.
Degludec achieves that with a chemical trick rather than a pump: a fatty acid chain attached to the molecule makes injected units link up into long strings the moment the preservative in the vial diffuses away. The string is a storage depot the body cannot absorb. Zinc leaks out of it slowly, and single insulin molecules peel off one end at a time, which is why one injection keeps working for the best part of two days.
Why people take it. Diabetes — the once-daily background insulin that lasts over 42 hours
What happened in people
A duration of glucose-lowering action beyond 42 hours and a steady-state half-life near 25 hours in a 21-patient euglycaemic clamp study on the FDA label
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
The limit that matters most
That degludec lowers HbA1c better than insulin glargine — the 52-week head-to-head difference was 0.08 percentage points in favour of glargine, and mean HbA1c in DEVOTE was identical at 7.5% in both arms
Where it acts
Subcutaneous depot, then circulating albumin, then insulin receptors on skeletal muscle, fat and liver cells
Kind of result
A number that stands in for health
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as protein.
FDA substance registry · 54Q18076QB · read 2026-08-29
Its recorded molecular formula is C274H411N65O81S6, weighing 6.104 kDa.
US prescribing information · e8ccd2f4-6ba9-4839-87f8-4742dc9b1c17 · read 2026-08-30
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 132 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 38 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Blood sugar
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
△Only a number moved15 registered test measure.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Blood sugar
extension trial cross reacting antibodies to human insulin; area under the glucose infusion rate curve; hba1c; hba1c at week 26; hba1c at 26 weeks; area under the insulin aspart concentration curve; area under the serum insulin aspart concentration time curve; hba1c 26 weeks after randomisation
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
△ Only a number moved
15 registered test measure.
— Not recorded
Harms were not a registered measure for this goal.
… Waiting for a reviewer
Who was studied is listed further down the page.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Time to first adjudicated major adverse cardiovascular event: cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, against a non-inferiority margin of 1.3
✓ The study showed what it set out to show
Who was studied
DEVOTE (NCT01959529)
How many people
7637
Study design
Phase 3 double-blind, treat-to-target, event-driven cardiovascular outcome trial, median 1.99 years
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
P < 0.001 for non-inferiority; hazard ratio 0.91 (95% CI 0.78 to 1.06). Adjudicated severe hypoglycaemia rate ratio 0.60, P < 0.001 for superiority
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The trial was designed to exclude harm, not to demonstrate benefit; the upper confidence bound of 1.06 is compatible with no cardiovascular effect in either direction. Mean HbA1c was identical in the two arms at 24 months.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Once-daily subcutaneous injection by prefilled pen or cartridge, in 100 units/mL and 200 units/mL presentations
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
Rate of overall severe or blood-glucose-confirmed symptomatic hypoglycaemic episodes during the maintenance period, in type 1 diabetes
✓ The study showed what it set out to show
Who was studied
SWITCH 1 (NCT02034513)
How many people
501
Study design
Double-blind randomised crossover non-inferiority trial, two 32-week periods
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
P < 0.001 for superiority; rate ratio 0.89 (95% CI 0.85 to 0.94). Severe hypoglycaemia 10.3% against 17.1%, McNemar P = 0.002
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Only 395 of 501 randomised patients (78.8%) completed the trial. Every participant had at least one hypoglycaemia risk factor by design, so the absolute rates do not describe an unselected population.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Once-daily subcutaneous injection by prefilled pen or cartridge, in 100 units/mL and 200 units/mL presentations
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
Rate of overall symptomatic hypoglycaemic episodes during the maintenance period, in type 2 diabetes
✓ The study showed what it set out to show
Who was studied
SWITCH 2 (NCT02030600)
How many people
721
Study design
Double-blind randomised crossover treat-to-target trial, two 32-week periods
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
P < 0.001; rate ratio 0.70 (95% CI 0.61 to 0.80). Nocturnal rate ratio 0.58 (95% CI 0.46 to 0.74), P < 0.001
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Severe hypoglycaemia — the endpoint that matters most — was 1.6% against 2.4% and was not statistically significant (McNemar P = 0.35). 580 of 721 patients (80.4%) completed.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Once-daily subcutaneous injection by prefilled pen or cartridge, in 100 units/mL and 200 units/mL presentations
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
Number of overall symptomatic hypoglycaemic events during the 36-week maintenance period, degludec U200 against glargine U300
✗ The study did not show it
Who was studied
CONCLUDE (NCT03078478)
How many people
1609
Study design
Open-label randomised treat-to-target head-to-head trial, up to 88 weeks
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Rate ratio 0.88 (95% CI 0.73 to 1.06) — not significant; the confirmatory testing procedure was stopped at this point
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. The prespecified confirmatory secondary endpoints were reclassified as exploratory once the primary failed. The severe-hypoglycaemia rate ratio of 0.20 (95% CI 0.07 to 0.57) that is often quoted comes from those exploratory analyses.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Once-daily subcutaneous injection by prefilled pen or cartridge, in 100 units/mL and 200 units/mL presentations
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
Estimated treatment difference 0.08 percentage points (95% CI -0.05 to 0.21), confirming non-inferiority. Overall confirmed hypoglycaemia rate ratio 0.82 (95% CI 0.69 to 0.99, P = 0.0359)
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The trial randomised 3:1 in favour of degludec, so the glargine comparator arm was 251 patients. Severe hypoglycaemia was 0.06 against 0.05 episodes per patient-year and the authors state these were too infrequent to assess a difference.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Once-daily subcutaneous injection by prefilled pen or cartridge, in 100 units/mL and 200 units/mL presentations
Interval reported. 95% CI -0
Written into the record, not signed off as a reviewed claim.
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
RNAWiki holds 5 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
□Living longer, or avoiding a major eventNo evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
□Symptoms and quality of lifeNo evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.23 registered measures of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
□AnimalsNo evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.No animal record is stored.
□Cells in a dishNo evidence recorded. Cells or chemistry on a bench, far from a whole body.No cell or bench record is stored.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Insulin degludec
What a person takes: Once-daily subcutaneous injection by prefilled pen or cartridge, in 100 units/mL and 200 units/mL presentations.
The measurement behind this step
A clear, colourless aqueous solution at pH approximately 7.6 containing glycerin, metacresol, phenol and zinc. The 200 units/mL presentation delivers the same total glucose-lowering effect as the 100 units/mL presentation at the same units/kg dose in clamp studies, in half the injected volume. Steady state is reached after three to four days, which is a property of the depot rather than of the dose.
Getting in
Injected as pairs of six-molecule clusters
In the pen the insulin is held as dihexamers — twelve molecules locked together around zinc, kept stable by a phenol preservative. That is a storage form, not a working form.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The formulation contains zinc at 32.7 micrograms per millilitre in the U-100 presentation, with phenol and metacresol as phenolic ligands holding the molecule in a soluble dihexamer at pH 7.6. Nothing in this state is absorbable or pharmacologically active.
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
Reaching the cell
The preservative leaks away and the clusters link into long chains
Under the skin the phenol diffuses out within minutes. That uncaps the ends of each cluster, and the clusters snap together end to end into strings thousands of units long. The strings are the depot.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Loss of the phenolic ligands opens the hexamer end faces. The hexadecanedioic acid side chain on lysine B29 of one hexamer inserts into the neighbouring hexamer, and the process repeats, producing soluble multi-hexamer chains. The FDA label states plainly that TRESIBA forms multi-hexamers on subcutaneous injection, and that the protracted profile is predominantly due to delayed absorption from this depot.
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
What it acts on
Zinc leaves slowly and single molecules peel off the ends
Zinc atoms diffuse out of the chain gradually. As they go, the chain unzips from its ends and releases single insulin molecules — a few at a time, for the best part of two days.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Zinc diffusion is the rate-limiting step of the entire pharmacokinetic profile. Terminal-end dissociation releases monomers at a near-constant rate, giving steady-state half-life of approximately 25 hours, a time to maximum effect near 12 hours and a duration beyond 42 hours, with a day-to-day within-subject coefficient of variation of 20%.
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
The change it makes
Albumin carries the released molecules and buffers the peak
The fatty acid chain that made the strings also sticks to the main protein in blood. More than 99% of the drug in circulation is bound to it at any moment, which smooths out whatever variation escapes the depot.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The diacid side chain binds serum albumin at an affinity corresponding to greater than 99% plasma protein binding, creating a circulating reservoir in equilibrium with free hormone. The label ranks this a secondary contributor to protraction; the subcutaneous depot does most of the work.
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
The change it makes
The free hormone acts at the same receptor as any other insulin
Once free, the molecule does exactly what ordinary insulin does: tells muscle and fat to take sugar in and tells the liver to stop making more. Nothing about the target has been changed.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Binding to the alpha subunits of the insulin receptor triggers beta-subunit autophosphorylation, IRS phosphorylation and PI3K-AKT signalling, driving GLUT4 translocation in muscle and adipose tissue and suppressing hepatic gluconeogenesis and lipolysis. Degradation is described on the label as similar to that of human insulin, with all metabolites inactive.
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
What that does for a person
Fasting glucose falls, night-time lows fall, average blood sugar does not move
The measured result is a flatter overnight profile: fewer low blood sugar episodes, particularly at night, and slightly lower fasting glucose. Average blood sugar over three months ends up the same as on the drug it replaced.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
In DEVOTE, mean fasting plasma glucose at 24 months was 128 against 136 mg/dL (p<0.001) while mean HbA1c was 7.5% in both arms. Adjudicated severe hypoglycaemia was 4.9% against 6.6%, rate ratio 0.60. In SWITCH 2, nocturnal symptomatic hypoglycaemia fell by 42% (rate ratio 0.58, 95% CI 0.46 to 0.74).
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
No registered study measured anything of this kind.
Measured
Things only a test, a scale or a device shows.
glycosylated haemoglobin
extension trial cross reacting antibodies to human insulin
area under the glucose infusion rate curve
hba1c
area under liraglutide concentration time curve
hba1c at week 26
hba1c at 26 weeks
area under the insulin aspart concentration curve
area under the serum insulin aspart concentration time curve
hba1c 26 weeks after randomisation
and 13 more.
Meaningful
Things that change how a life goes, not only a number.
No registered study measured anything of this kind.
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (15)
rate of major and minor hypoglycaemic episodes
rate of nocturnal major and minor hypoglycaemic episodes
extension trial rate of confirmed hypoglycaemic episodes
rate of treatment emergent adverse events
extension trial rate of treatment emergent adverse events
average time within glycaemic target range
frequency of adverse events
adverse events
incidence of adverse events by preferred term
treatment emergent adverse events
symptomatic nocturnal hypoglycaemia
time in range
glycemic variability
incidence of adverse events
part 1 sad number of adverse events
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What it would be like to take◇Read from sources, not yet reviewed
How long anything takes
Nine different lengths of time that get confused with each other. None of them is worked out from another.
Before anything is noticed.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before a test result moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before performance moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
How long the result was watched.No finished study window is recorded for a study that tested this substance.
How long people took it.How long people actually took it is not stored. The study window is not the same thing.
How long people were followed.Follow-up length is not stored separately. It is never read off the study window, which would be a different thing.
How fast the body clears it. 25 hours hours
Read from the label, which states: “On average, the half-life at steady state is approximately 25 hours independent of dose.”
How long effects linger.RNAWiki does not store this separately, and never works it out from another figure on this page.
Beyond the studies. Nothing is recorded about the long term.
The longest finished study sets the edge of what anyone measured.
A study window is not how long people took it, and neither is how long they were followed. Where RNAWiki holds only one of the three, it shows one.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
People with type 1 diabetes, as the background half of a basal-bolus regimen, and people with type 2 diabetes whose tablets no longer hold the fasting glucose down. Licensed in the United States down to one year of age.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety and effectiveness of TRESIBA have not been established in pediatric patients less than 1-year-old.”
US prescribing information · e8ccd2f4-6ba9-4839-87f8-4742dc9b1c17 · read 2026-08-30
On older people, the label states: “In controlled clinical trials [see Clinical Studies ( 14 )] a total of 77 (7%) of the 1102 TRESIBA-treated patients with type 1 diabetes were 65 years or older and 9 (1%) were 75 years or older.”
US prescribing information · e8ccd2f4-6ba9-4839-87f8-4742dc9b1c17 · read 2026-08-30
On people who are pregnant, the label states: “Human insulin (NPH insulin) was included as comparator.”
US prescribing information · e8ccd2f4-6ba9-4839-87f8-4742dc9b1c17 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There are no data on the presence of insulin degludec in human milk, the effects on the breastfed infant, or the effects on milk production.”
US prescribing information · e8ccd2f4-6ba9-4839-87f8-4742dc9b1c17 · read 2026-08-30
On people with reduced liver function, the label states: “No difference in the pharmacokinetics of TRESIBA was identified in a study comparing healthy subjects and subjects with hepatic impairment (mild, moderate, and severe hepatic impairment) [see Clinical Pharmacology ( 12.3 )] .”
US prescribing information · e8ccd2f4-6ba9-4839-87f8-4742dc9b1c17 · read 2026-08-30
On people with reduced kidney function, the label states: “In clinical trials [see Clinical Studies ( 14 )] a total of 75 (7%) of the 1102 TRESIBA-treated patients with type 1 diabetes had an eGFR less than 60 mL/min/1.73 m 2 and 1 (0.1%) had an eGFR less than 30 mL/min/1.73 m 2 .”
US prescribing information · e8ccd2f4-6ba9-4839-87f8-4742dc9b1c17 · read 2026-08-30
Where the result stopped carrying
The FDA refused the application on 8 February 2013 after identifying a signal of serious cardiovascular risk in its own meta-analysis of the degludec trial programme, delaying approval by two and a half years and imposing a required outcome trial
CONCLUDE failed its primary endpoint against glargine U300 (rate ratio 0.88, 95% CI 0.73 to 1.06), which stopped the confirmatory testing procedure and demoted every secondary result to exploratory
Severe hypoglycaemia in SWITCH 2 — 1.6% against 2.4% — did not reach significance, so the type 2 hypoglycaemia case rests on overall and nocturnal episode counts rather than on the severe ones
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Once-daily subcutaneous injection by prefilled pen or cartridge, in 100 units/mL and 200 units/mL presentations
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S9.
No source is stored against this line.
What is in the pack
6 containing glycerin, metacresol, phenol and zinc.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: The 200 units/mL presentation delivers the same total glucose-lowering effect as the 100 units/mL presentation at the same units/kg dose in clamp studies, in half the injected volume. Steady state is reached after three to four days, which is a property of the depot rather than of the dose.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Hypoglycaemia is the commonest and most serious adverse effect of every insulin and is dose-related rather than analogue-specific. Hypokalaemia can follow any insulin dose. Injection-site reactions, lipodystrophy, peripheral oedema and weight gain occur. Hypersensitivity reactions including anaphylaxis are rare. Not recommended for diabetic ketoacidosis. The 100 and 200 units/mL pens deliver different volumes for the same number of units, and the two must not be confused; product-name and concentration confusion between insulins is a recognised dispensing hazard.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
DEVOTE: A Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Event… · a recorded source, not a stored snapshot
Lane W, Bailey TS, Gerety G et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomi… · a recorded source, not a stored snapshot
Reports sent to a regulator
These are reports people sent to a regulator. They do not show the medicine caused the reaction.
Nobody counted how many people took the medicine and reported nothing.
The same event can be reported more than once, and many reports are incomplete.
News coverage, lawsuits and new warnings change how often people report.
A count is not a rate and not a risk.
Insulin degludec appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 2361 reaction mentions were counted. One report can name several reactions.
The recorded terms (10)
hypoglycaemia — 884 reaction mentions
blood glucose increased — 269 reaction mentions
premature baby — 241 reaction mentions
blood glucose decreased — 189 reaction mentions
diabetic ketoacidosis — 162 reaction mentions
premature delivery — 159 reaction mentions
hyperglycaemia — 153 reaction mentions
diabetes mellitus inadequate control — 121 reaction mentions
open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Once-daily subcutaneous injection by prefilled pen or cartridge, in 100 units/mL and 200 units/mL presentations
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
6 containing glycerin, metacresol, phenol and zinc.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold. The rest of the recorded wording: The 200 units/mL presentation delivers the same total glucose-lowering effect as the 100 units/mL presentation at the same units/kg dose in clamp studies, in half the injected volume. Steady state is reached after three to four days, which is a property of the depot rather than of the dose.
No source is stored against this line.
What is recorded as being sold
14 products list this as an active ingredient in the United States drug directory. 13 of them contain it and nothing else.
FDA National Drug Code directory · 0169-2660 · read 2026-08-29
They are sold as injection, solution and powder, taken subcutaneous.
FDA National Drug Code directory · 0169-2660 · read 2026-08-29
The regulator's established pharmacologic class for it is insulin analog [epc] and insulin [cs].
FDA National Drug Code directory · 0169-2660 · read 2026-08-29
7 published labels name it as an active ingredient. 6 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · e8ccd2f4-6ba9-4839-87f8-4742dc9b1c17 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · e8ccd2f4-6ba9-4839-87f8-4742dc9b1c17 · read 2026-08-29
901 marketed supplement labels list this ingredient, classed as botanical, non-nutrient/non-botanical and other combinations.
Those labels carry all other and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
TRESIBA is subcutaneous at 3 DOSAGE FORMS AND STRENGTHS Injection: Available as a clear and colorless solution: • 100 units/mL (U-100): 3 mL single-patient-use FlexTouch prefilled pen • 100 units/mL (U-100): 10 mL multiple-dose vial • 200 units/m…, recorded as fda label in effect 2024-02-22 in the United States.
US prescribing information · e8ccd2f4-6ba9-4839-87f8-4742dc9b1c17 · read 2026-08-30
Recorded price in US: 11.3401 USD per one millilitre, for the one priced product, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Insulin degludec studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That degludec lowers HbA1c better than insulin glargine — the 52-week head-to-head difference was 0.08 percentage points in favour of glargine, and mean HbA1c in DEVOTE was identical at 7.5% in both arms
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That degludec reduces cardiovascular events — DEVOTE was a non-inferiority trial designed to exclude a hazard ratio above 1.3, and its confidence interval reaches 1.06
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the severe-hypoglycaemia advantage carries over against insulin glargine U300 — CONCLUDE tested exactly that and missed its primary endpoint
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a 42-hour duration makes injection timing flexible in ordinary use; the clamp measurement was made after eight consecutive daily doses under supervision
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
How much did people take in the studies?
The sources RNAWiki checked hold nothing for this field.
Why it matters. A result belongs to an amount. Without the amount the result floats free.
What would answer it
A stored source that records it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Insulin degludec are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
The FDA refused it in 2013 over a cardiovascular signal it had found itself
In plain words
The application went in in 2011. Instead of approving it, the FDA wrote back in February 2013 saying its own pooled analysis of the trials had turned up a possible excess of heart attacks and strokes, and that only a new trial could settle it. Approval came two and a half years later, conditional on running that trial.
What was measured
Dates of the regulatory actions, and the text of the required postmarketing cardiovascular outcome trial
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The NDA for Tresiba was received on 29 September 2011. The FDA issued a complete response action letter on 8 February 2013; Novo Nordisk submitted its complete response on 26 March 2015 and the drug was approved on 25 September 2015. The approval letter states in terms that "a signal of a serious risk of cardiovascular events was identified from a meta-analysis of data from clinical trials evaluating insulin degludec and insulin degludec and insulin aspart, and available data have not definitively excluded the potential for this serious risk." It records that spontaneous adverse-event reporting and the Sentinel pharmacovigilance system were both judged insufficient, and imposes postmarketing requirement 2954-2 under section 505(o): a randomised, double-blind, active-controlled trial whose objective is to show the upper bound of the two-sided 95% confidence interval for adjudicated MACE is below 1.3. That trial is DEVOTE.
Source
FDA approval letter, NDA 203314, 25 September 2015 (Reference ID 3825141), postmarketing requirement 2954-2
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
DEVOTE cleared the cardiovascular signal and cut severe hypoglycaemia by 40%
In plain words
The trial the FDA demanded enrolled 7,637 people with type 2 diabetes, most of whom already had heart or kidney disease, and compared degludec against glargine for about two years. Heart attacks, strokes and cardiovascular deaths came out the same. Severe low blood sugar episodes were 40% less frequent on degludec.
What was measured
Hazard ratio for adjudicated three-point MACE, and rate and odds ratios for adjudicated severe hypoglycaemia over a median 1.99 years
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
DEVOTE (NCT01959529) randomised 7,637 patients with type 2 diabetes to insulin degludec (3,818) or insulin glargine U100 (3,819) once daily in a double-blind, treat-to-target, event-driven cardiovascular outcome trial. 6,509 participants (85.2%) had established cardiovascular disease, chronic kidney disease or both; mean age 65.0 years, mean diabetes duration 16.4 years, mean HbA1c 8.4%. The primary composite outcome occurred in 325 (8.5%) on degludec and 356 (9.3%) on glargine — hazard ratio 0.91 (95% CI 0.78 to 1.06, p<0.001 for non-inferiority). At 24 months mean HbA1c was 7.5% in both groups; mean fasting plasma glucose was lower on degludec, 128 against 136 mg/dL (p<0.001). Prespecified adjudicated severe hypoglycaemia occurred in 187 (4.9%) against 252 (6.6%), an absolute difference of 1.7 percentage points, rate ratio 0.60 (p<0.001 for superiority), odds ratio 0.73 (p<0.001 for superiority). Rates of adverse events did not differ.
Written into the record, not signed off as a reviewed claim
It never lowered HbA1c more than glargine, and was not designed to
In plain words
Every head-to-head trial was built to show degludec was no worse than glargine at controlling average blood sugar, not better. It was no worse. The difference in the 52-week trial was eight hundredths of a percentage point, with a confidence interval running through zero.
What was measured
That degludec controls blood sugar better than insulin glargine — no trial has shown this, all of them were designed as non-inferiority trials, and the point estimate in the 52-week trial favours glargine by 0.08 percentage points
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
BEGIN Basal-Bolus Type 2 (NCT00972283) randomised 1,006 adults with type 2 diabetes 3:1 to degludec or glargine, each with mealtime insulin aspart, in a 52-week open-label treat-to-target non-inferiority trial at 123 sites in 12 countries. HbA1c fell by 1.1% on degludec and 1.2% on glargine; the estimated treatment difference was 0.08 percentage points (95% CI -0.05 to 0.21), confirming non-inferiority against a limit of 0.4%. Overall confirmed hypoglycaemia was 11.1 against 13.6 episodes per patient-year (rate ratio 0.82, 95% CI 0.69 to 0.99, p=0.0359) and nocturnal confirmed hypoglycaemia 1.4 against 1.8 (rate ratio 0.75, 95% CI 0.58 to 0.99, p=0.0399). The authors noted severe hypoglycaemia rates "seemed similar" — 0.06 against 0.05 episodes per patient-year — "but were too low for assessment of differences." In DEVOTE, with 7,637 patients and a treat-to-target design, mean HbA1c at 24 months was 7.5% in both arms.
Written into the record, not signed off as a reviewed claim
The two SWITCH trials counted hypoglycaemia under blinding, and it fell
In plain words
Two crossover trials gave every participant both insulins in turn, with neither patient nor doctor knowing which was which, and counted low blood sugar episodes. Overall episodes fell 11% in type 1 diabetes and 30% in type 2. Night-time episodes fell by a third and by 42%.
What was measured
Rate ratios for overall and nocturnal symptomatic hypoglycaemia during blinded crossover maintenance periods, and the proportion of patients with severe hypoglycaemia
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
SWITCH 1 (NCT02034513) enrolled 501 adults with type 1 diabetes and at least one hypoglycaemia risk factor in a double-blind crossover trial of two 32-week periods. During the maintenance periods, overall severe or blood-glucose-confirmed symptomatic hypoglycaemia was 2,200.9 against 2,462.7 episodes per 100 person-years, rate ratio 0.89 (95% CI 0.85 to 0.94, p<0.001 for superiority); nocturnal episodes 277.1 against 428.6 per 100 person-years, rate ratio 0.64 (95% CI 0.56 to 0.73, p<0.001); severe hypoglycaemia in 10.3% against 17.1% of patients (McNemar p=0.002, risk difference -6.8%, 95% CI -10.8% to -2.7%). SWITCH 2 (NCT02030600) ran the same design in 721 adults with type 2 diabetes at 152 United States centres: overall symptomatic hypoglycaemia 185.6 against 265.4 episodes per 100 patient-years, rate ratio 0.70 (95% CI 0.61 to 0.80, p<0.001); nocturnal 55.2 against 93.6, rate ratio 0.58 (95% CI 0.46 to 0.74, p<0.001). Severe hypoglycaemia in SWITCH 2 was 1.6% against 2.4% and was not statistically significant (McNemar p=0.35, risk difference -0.8%, 95% CI -2.2% to 0.5%).
Written into the record, not signed off as a reviewed claim
Against the newer concentrated glargine, CONCLUDE missed its primary endpoint
In plain words
When degludec was tested against a more concentrated version of glargine rather than the original, the hypoglycaemia advantage vanished. The trial did not meet its main endpoint, and the statistical testing was stopped there. Everything reported afterwards is exploratory.
What was measured
Rate ratio for overall symptomatic hypoglycaemia in the 36-week maintenance period against insulin glargine U300
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
CONCLUDE (NCT03078478) randomised 1,609 insulin-treated adults with type 2 diabetes, HbA1c 9.5% or below, BMI 45 or below and at least one predefined hypoglycaemia risk factor, open-label 1:1 to degludec 200 U/mL or glargine 300 U/mL, both titrated to the same fasting target. The primary endpoint — number of overall symptomatic hypoglycaemic events during the 36-week maintenance period — gave a rate ratio of 0.88 (95% CI 0.73 to 1.06), not significant. The authors state that because there was no significant difference on the primary endpoint, the confirmatory testing procedure for superiority was stopped, and the prespecified confirmatory secondary endpoints "were now considered exploratory." Those exploratory analyses showed nocturnal symptomatic hypoglycaemia at rate ratio 0.63 (95% CI 0.48 to 0.84) and severe hypoglycaemia at rate ratio 0.20 (95% CI 0.07 to 0.57). A severe-hypoglycaemia rate ratio of 0.20 is a large number, and it carries no confirmatory weight, because the gate it had to pass through did not open.
Written into the record, not signed off as a reviewed claim
The 42-hour duration is a clamp-study measurement, not a marketing claim
In plain words
A glucose clamp study in 21 people with type 1 diabetes measured how long one injection kept working after eight daily doses. The answer was at least 42 hours, with the strongest effect at around 12 hours and day-to-day variability of 20%.
What was measured
Duration of glucose-lowering effect, time to maximum glucose infusion rate, day-to-day coefficient of variation and steady-state half-life in a euglycaemic clamp study
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The FDA label for Tresiba reports a euglycaemic glucose clamp study in 21 patients with type 1 diabetes after eight once-daily subcutaneous doses of 0.4 units/kg. Maximum glucose infusion rate was 2.0 mg/kg/min at a median of 12 hours post-dose, and the glucose-lowering effect lasted at least 42 hours after the last injection. Steady-state within-subject day-to-day variability in total glucose-lowering effect was 20% (coefficient of variation for AUC-GIR). Steady state was reached after three to four days. Half-life at steady state is approximately 25 hours, determined primarily by the rate of absorption from subcutaneous tissue rather than by clearance. Albumin affinity corresponds to greater than 99% plasma protein binding. The label attributes the protracted profile predominantly to delayed subcutaneous absorption and only to a lesser extent to albumin binding.
Source
FDA prescribing information for TRESIBA (insulin degludec injection), sections 11, 12.1, 12.2 and 12.3, NDA 203314
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
How many documents were read
6 documents were read for this substance.
RNAWiki source record
6 of them state the same halfLife, and they agree.
RNAWiki source record
6 of them state the same proteinBinding, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
54Q18076QB
RxNorm concept
1670021
Checks this page had to pass
✓ Passed
Identity resolved
no open identity hold
✓ Passed
No unresolved merge across substance families
no quarantine open
✓ Passed
Every public sentence names a source
The opening statement carries the origin: Written into the record, not signed off.
✗ Not passed
Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
✓ Passed
No internal keys in reader text
enforced by the copy-contract test over the rendered page
✓ Passed
Safety mode resolved
Suppression classes recorded: S9.
✓ Passed
Canonical metadata present
slug and display name present
What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
3 approved applications cover products containing this substance. The earliest was BLA203313, approved 20150925 to NOVO.
This order is fixed in code and does not count clicks or time on the page.
What is not here
3 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
Human insulin with the last amino acid of the B chain removed and a 16-carbon diacid chain bolted on, so that the molecule self-assembles into long multi-hexamer chains under the skin and dissolves out of them over more than 42 hours — a design that reduced overall symptomatic hypoglycaemia by 30% against insulin glargine in 721 randomised adults with type 2 diabetes, produced no HbA1c advantage at all, and was refused approval for two and a half years while the FDA required a 7,637-patient cardiovascular outcome trial that ultimately returned a hazard ratio of 0.91.
Recorded evidence blocks (10)
Q2
What did Insulin degludec's largest trial (7637 people) and its longest (5.5 years) measure?
7637 people in Insulin degludec's largest registered study, 5.5 years in its longest registered window, measuring Area under the Insulin Degludec concentration-time curve from 0 to 120 hours after single dose. ClinicalTrials.gov · 2026-09-01
58 phase3, 48 phase1, 18 phase4, 12 na or unstated, 11 phase2, 1 early phase1, 1 na; NCT01984372; 2019-04-30; no ageing endpoint recorded. Last human test completed 2026, NCT06685185.
Interpretation These counts include studies where Insulin degludec was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase3
58
phase1
48
phase4
18
na or unstated
12
phase2
11
early phase1
1
2 more recorded rows
na
1
Last recorded human testNCT06685185
2026-03-18
recorded 2026-09-01 · last checked 2026-09-04
Q3
Insulin degludec was tested only in human — what did it show?
Area under the Insulin Degludec concentration-time curve from 0 to 120 hours after single dose — the recorded outcome words.
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humanNCT00966368
biomarker; Area under the Insulin Degludec concentration-time curve from 0 to 120 hours after single dose; 148
recorded 2026-09-01 · last checked 2026-09-04
Q4
3 of Insulin degludec's trials stopped: safety, accrual/recruitment, other?
safety (1), accrual/recruitment (1) and other (1): Insulin degludec's stop wording, clustered. ClinicalTrials.gov · 2026-09-01
"This trial was terminated due to low recruitment"; 3 of 148 registered studies
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Trial
NCT01467414
terminated; "This trial was terminated due to low recruitment"
NCT03349840
terminated; "The study was terminated by the IRB and the Institutional Official after the MOPH and WCMQ audits"
NCT05552859
terminated; "Sponsor decision to cancel trial due to poor recruitment/ severe recruitment delay and not related to safety concern."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Insulin degludec's half-life is 25 hours — which schedules were studied?
25 hours, the half-life Insulin degludec's label states. openfda-label · 7a4bd8e5-7af4-4573-97c2-9945faf6a7dd · 2026-08-30
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half life
25 hours hours; On average, the half-life at steady state is approximately 25 hours independent of dose.
tmax
Figure 2: Mean GIR profile for 0.4 U/kg dose of TRESIBA (steady state) in patients with Type 1 diabetes mellitus 12.3 Pharmacokinetics Absorption In patients with type 1 diabetes, after 8 days of once daily subcutaneous dosing with 0.4 units/kg of Insulin Degludec, maximum degludec concentrations of 4472 pmol/L were attained at a median of 9 hours (t max ).
metabolism
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The primary activity of insulin, including Insulin Degludec, is regulation of glucose metabolism.
recorded 2026-08-30 · last checked 2026-09-04
Q6
Which of adverse events, area under liraglutide concentration time curve and area under the glucose infusion rate curve did Insulin degludec's trials measure?
adverse events, area under liraglutide concentration time curve and area under the glucose infusion rate curve lead 38 outcome terms across Insulin degludec's trials. ClinicalTrials.gov · 2026-09-01
extension trial rate of confirmed hypoglycaemic episodes, rate of treatment emergent adverse events, extension trial rate of treatment emergent adverse events, extension trial cross reacting antibodies to human insulin, area under the glucose infusion rate curve and hba1c follow.
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glycosylated haemoglobin
1
rate of major and minor hypoglycaemic episodes
1
rate of nocturnal major and minor hypoglycaemic episodes
1
extension trial rate of confirmed hypoglycaemic episodes
1
rate of treatment emergent adverse events
1
extension trial rate of treatment emergent adverse events
1
14 more recorded rows
extension trial cross reacting antibodies to human insulin
1
area under the glucose infusion rate curve
1
hba1c
1
area under liraglutide concentration time curve
1
hba1c at week 26
1
hba1c at 26 weeks
1
average time within glycaemic target range
1
frequency of adverse events
1
adverse events
1
area under the insulin aspart concentration curve
1
area under the serum insulin aspart concentration time curve
1
incidence of adverse events by preferred term
1
treatment emergent adverse events
1
symptomatic nocturnal hypoglycaemia
1
recorded 2026-09-01 · last checked 2026-09-04
Q7
Which of Insulin degludec's 6 ongoing trials reports first?
Part A: Number of participants with one or more Adverse Event (s) (AEs), and Serious Adverse Event(s) (SAEs) considered by the investigator to be related to study drug…; Change in HbA1c; latest 2027-04-17
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Trial
NCT06280703
"A Study of LY3938577 in Healthy Participants and Participants With Type 1 Diabetes Mellitus (T1DM)"; n 118; "Part A: Number of participants with one or more Adverse Event (s) (AEs), and Serious Adverse Event(s) (SAEs) considered by the investigator to be related to study drug administration."; 2026-09
NCT06767748
"A Phase III Clinical Study to Assess the Efficacy and Safety of GZR4 in Subjects With Type 2 Diabetes Mellitus Treated With Basal Insulin"; n 620; "Change in HbA1c"; 2026-02-28
NCT07018453
"A Study Comparing SHR-3167 and Insulin Degludec in Type 2 Diabetic Subjects Treated With Basal Insulin With or Without Oral Antidiabetic Drugs"; n 173; "Change in glycosylated hemoglobin (HbA1c) from baseline."; 2026-05
NCT07032688
"A Clinical Study to Evaluate the Pharmacokinetic and Pharmacodynamics Properties of of SHR-3167 in Subjects With Type 2 Diabetes"; n 55; "Area under the SHR-3167 concentration-time curve (AUC SHR-3167, tau, ss)."; 2027-04
NCT07527078
"Evaluate the Efficacy and Safety of GZR33 Injection in Patients With Type 2 Diabetes"; n 350; "Change in Hemoglobin A1c (HbA1c) from baseline after 26 weeks of treatment."; 2027-04-17
NCT07630233
"A Phase I Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Subcutaneous UBT38006 Injection in Healthy Adult Males"; n 53; "incidence of adverse events (AEs), adverse drug reactions (ADRs), serious adverse events (SAEs), etc,.."; 2026-10-25
recorded 2026-09-01 · last checked 2026-09-04
Q8
Which 63 trials of Insulin degludec posted no result?
Posted no result
63 of 63 completed trials
Registrations
NCT01865279, NCT01865292, NCT01865318, NCT01865305, NCT01865331 and NCT01868555, and 57 more
Completion dates
oldest 2006-04; newest 2024-08-08
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Trial
NCT01865279
2006-04
NCT01865292
2006-11
NCT01865318
2007-01
NCT01865305
2007-02
NCT01865331
2007-03
NCT01868555
2008-02
14 further recorded trials
NCT01868529
2008-06
NCT01868568
2008-08
NCT01868581
2008-08
NCT00964964
2009-09
NCT00966368
2009-10
NCT00961324
2009-10-26
NCT00964418
2009-11
NCT00983021
2009-12
NCT00992537
2010-01
NCT00976326
2010-03
NCT01002768
2010-03
NCT01006057
2010-05
NCT01030926
2010-05
NCT01076634
2010-07
Q9
At the median, Insulin degludec's trials enrolled 179 people — anything larger?
Median enrolment
179
Largest enrolment
7637
Registered trials counted
148
Q10
What do 2361 spontaneous reports say about Insulin degludec — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Insulin degludec appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 2361 reaction mentions were counted: hypoglycaemia 884; blood glucose increased 269; premature baby 241; blood glucose decreased 189. open-targets-adr · CHEMBL2107869 · 2026-06-24
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hypoglycaemia
884
blood glucose increased
269
premature baby
241
blood glucose decreased
189
diabetic ketoacidosis
162
premature delivery
159
4 more recorded rows
hyperglycaemia
153
diabetes mellitus inadequate control
121
glycosylated haemoglobin increased
97
low birth weight baby
86
recorded 2026-06-24 · last checked 2026-09-04
Q11
Was Insulin degludec studied with fasting and exercise?
fasting and exercise are named in Insulin degludec's label sentences: "This post hoc analysis assessed change from baseline to week 52 in glycemic parameters for tirzepatide (5, 10, 15 mg) versus insulin degludec (SURPASS-3 trial) and glargine (SURPASS-4 trial) in people with type 2 diabetes and different baseline glycemic patterns, based on fasting serum glucose…" openfda-label+europepmc · 2024-06-01
2 recorded statements; fasting, exercise
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fasting
This post hoc analysis assessed change from baseline to week 52 in glycemic parameters for tirzepatide (5, 10, 15 mg) versus insulin degludec (SURPASS-3 trial) and glargine (SURPASS-4 trial) in people with type 2 diabetes and different baseline glycemic patterns, based on fasting serum glucose (FSG) and postprandial glucose (PPG) values.
exercise
The ADREM study (Adjustment of insulin Degludec to Reduce post-Exercise (nocturnal) hypoglycaeMia in people with diabetes) was a randomised controlled, crossover study in which we compared 40% dose reduction (D40), or postponement and 20% dose reduction (D20-P), with no dose adjustment (CON) in adults with type 1 diabetes at elevated risk of hypoglycaemia, who performed a 45 min aerobic exercise…
recorded 2024-06-01 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
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