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Semaglutide

Discussion in 'Other Diabetic Medications' started by LittleGreyCat, Jul 7, 2019.

  1. LittleGreyCat

    LittleGreyCat Type 2 · Well-Known Member

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    Came across this after following a link to local research projects from another thread.

    Wikipedia link https://en.wikipedia.org/wiki/Semaglutide

    Initially there seem to be some good things about it.

    • GLP-1 look alike with minor modification to prevent enzymatic removal from the blood stream.
    • Lasts about a week between injections.
    • Increases insulin secretion.
    • Can encourage regeneration of Beta cells!
    • Inhibits glucagon production (which increase BG levels as an opposite to insulin which lowers them).

    Hmmm.....any side effects?

    "Semaglutide has minor adverse effects. Nausea, vomiting, diarrhea, abdominal pain, and constipation are usually experienced.[20] In patients with heart (cardiovascular) problem, it causes retinal (eye) damage (retinopathy)."

    I was considering it no worse than Metformin until I read the bit about retinopathy.

    Anyone been using this long term?

    At the moment (from using my first Freestyle Libre) I am wondering if I am over producing glucagon.

    However I have read that stimulating the pancreas can lead to increased loss of beta cells over time.

    So possibly not a magic cure.
     
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  2. SimonCrox

    SimonCrox · Well-Known Member

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    Semaglutide is really interesting because in SUSTAIN 6 it reduced adverse cardiovascualr outcomes:-

    https://www.nejm.org/doi/full/10.1056/NEJMoa1607141

    This is of crucial importance since diabetic folk are at increased risk of heart attack and stroke.

    Interestingly, semaglutide can be given orally (although not available yet) and reduces adverse events slightly - this was not so significant as in SUSTAIN 6, but the study was of far shorter duration.

    https://www.nejm.org/doi/10.1056/NEJMoa1901118

    To put things in perspective, liraglutide and dulaglutide decrease adverse CV outcomes whaereas exenatide and lixesenatide do not. If you look at the names, -glutide drugs are good (derived from human GLP-1) and -natide drugs (derived from exendin 4 in gila maonster saliva) do not have the CV protection.

    Some tablets, SGLT-2 inhibitors, and pioglitazone and probably metformin decrease CV events. It is handy that we have a large selection of drugs available if diet / lifestyle do not do the trick

    Semaglutide has been on the UK market since early this year, I think, so would be interesting to hear peoples' experience of it.

    One of the features of T2DM is that the body fails to suppress glucagon levels after meals whereas in non-diabetic people, the glucagon level drops a bit after meals - supplementing GLP-1 prevents the rise in glucoagon and supplements the rise in insulin after meals.

    Thanks for pointing out about the retinopathy; Diabetic retinopathy complications occurred in 50 patients (3.0%) in the semaglutide group and 29 (1.8%) in the placebo group (hazard ratio, 1.76; 95% CI, 1.11 to 2.78; P=0.02). The cause of this was not clear, and the autohrs wondered if it might have been due to rapid improvement in HbA1c. Certainly something to be aware of. Conversely, I think that there was less nephropathy on the semaglutide . I don't think this was seen on the other agents' trials, but I will go and look them up

    Thanks for interesting post

    Best wishes
     
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  3. DCUKMod

    DCUKMod I reversed my Type 2 · Master
    Staff Member Administrator

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    @LittleGreyCat , in addition to the comments made by @SimonCrox , I'd be interested to know if those retinopathy changes persisted beyond the screening done to find them.

    Some people find reducing their A1c quickly can "bring on" (evidence of) retinopathy, but find it to be gone at the next screening. Similarly, there was a paper noted a thread about unexpected retinopathy, a year or so ago, that suggested that retinopathy could be indicative of glucose levels much further back that the recent past.

    I'm certainly not rubbishing the findings, or anyone's experience on that medication, but just pondering how they can be so certain Semaglutide caused the retinopathy, rather than it being incidental, or caused by some other, unrecognised factor.
     
  4. LittleGreyCat

    LittleGreyCat Type 2 · Well-Known Member

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    @DCUKMod I had a finding of signs of background retinopathy at my last photographic eye screening when my BG was out of control for a few months, but by the time of my eye appointment a very thorough going over could find no sign.

    In my particular case I don't think a rapid reduction of HbA1c is on the cards as I have (hopefully) reestablished control now.

    @SimonCrox I am now intrigued by the long term study after the Semaglutide has been approved. Although there are still long term studies of other prescription drugs, and quite right too!

    It does open the temptation to approach my GP and talk about using it.
    Then again I am a wuss with needles.

    Do you have a pointer to a source which compares and contrasts various "glutides"?

    If my amateur self analysis is correct and I am over producing glucagon then the claimed benefits seem to fit my needs (as long as there aren't any major downsides).

    Without prejudice, would it be advisable to discuss this with an endocrinologist who specialises in diabetes who may be more up to date with recent research than a local GP? Assuming that the local GP is not a diabetes specialist, obviously.

    Edit: forgot to say "thank you" for the links.
     
  5. SimonCrox

    SimonCrox · Well-Known Member

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    The retinopathy was often persistent and thought to need treatment:-

    Diabetic retinopathy complications occurred in 50 patients (3.0%) in the semaglutide group and 29 (1.8%) in the placebo group (hazard ratio, 1.76; 95% CI, 1.11 to 2.78; P=0.02) (Table 2, and Table S9 and Fig. S5 in the Supplementary Appendix). The treatment difference between groups was first seen very early in the trial. The numbers of patients who required retinal photocoagulation were 38 (2.3%) in the semaglutide group versus 20 (1.2%) in the placebo group, the numbers of those who required the use of an intravitreal agent were 16 (1.0%) versus 13 (0.8%), the numbers of those who had a vitreous hemorrhage were 16 (1.0%) versus 7 (0.4%), and the numbers of those who had an onset of diabetes-related blindness were 5 (0.3%) versus 1 (0.1%) (Table S9 in the Supplementary Appendix). Of the 79 patients with retinopathy complications, 66 (83.5%) had preexisting retinopathy at baseline (42 of 50 [84.0%] in the semaglutide group and 24 of 29 [82.8%] in the placebo group). New or worsening nephropathy occurred in 62 patients (3.8%) in the semaglutide group and 100 (6.1%) in the placebo group (hazard ratio, 0.64; 95% CI, 0.46 to 0.88; P=0.005) (Table 2, and Table S9 and Fig. S5 in the Supplementary Appendix).

    There is always the problem of multpile statistical tests - if one takes the data and tests lots of questions on it, there may be a significant P value not because of a genuine link, but because a P value of say 5%, 1 in 20, will occur purely by chance about 1 test in 20.

    Not got around to looking at the other GLP-1 analogue studies - sorry

    best wishes
     

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  6. SimonCrox

    SimonCrox · Well-Known Member

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    The LEADER Trial of Liraglutide ( https://www.nejm.org/doi/full/10.1056/NEJMoa1603827 ) showed a reduction in nephropathy but a slight, non-significant increase in retinopathy; it also showed a reduction in any death, heart attack and stroke which was significant and far greater than the extra 0.1 people per 100 patient years getting retinopathy.

    The Dulaglutide REWIND trial is not available for free, but the abstract does not mention retinopathy.
     
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  7. LittleGreyCat

    LittleGreyCat Type 2 · Well-Known Member

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    I note, however, that Liraglutide is not a preferred option.
    https://en.wikipedia.org/wiki/Liraglutide as the usual (sometimes reliable) source.
    "In diabetes it is a less preferred agent.[1][2] Its effects on long term health outcomes like heart disease and life expectancy are unclear.".

    Also, "Common side effects include low blood sugar, nausea, dizziness, abdominal pain, and pain at the site of injection.[1] Other serious side effects may include medullary thyroid cancer, angioedema, pancreatitis, gallbladder disease, and kidney problems.[1] Use in pregnancy and breastfeeding is of unclear safety.[1] Liraglutide is a glucagon-like peptide-1 receptor agonist(GLP-1 receptor agonist) also known as incretinmimetics.[1] It works by increasing insulin release from the pancreas and decreases excessive glucagon release.[1]".

    The side effects look a bit scary, and worse than those listed for Semaglutide. In fact Semaglutide is supposed to improve kidney function instead of potentially causing problems.

    Finally "In diabetes it is a less preferred agent.[1] It may be used in those in who metformin and another antidiabetic medication such as a sulfonylurea are not sufficient.".

    Perhaps wrongly, I was looking for a form of medication which helped balance my insulin and glucagon production (as suggested by my current Libre readings) instead of just kicking my pancreas to produce more insulin (with consequent hypo risks) and the possibility of having to notify DVLA if I have uncontrolled hypos.
    I note from my Libre (although it is still reading lower than finger pricks) that I do have lows in BG around midnight some nights.

    However I think that most of the "glutides" seem to be 3rd line options if Metformin + Sulphonylureas combined don't work.

    I was hoping that Semaglutide might be an option which didn't rely on Sulphonylureas failing to work adequately.

    Transitioning from Metformin and exercise to more aggressive medication seems to be a minefield.

    @DCUKMod as well. :)
     
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