Anyone on the Ascend Plus trial?

[MrsBezzer]

I think the key here is that you should be talking about blood sugar control and not weight loss. If you are on the Ascend Plus trial it is for people with Type 2 diabetes. There are also more effective drugs for weight loss available through private prescription.

Rybelsus is not allowed to be prescribed for weight loss on the NHS, but it is prescribed for blood sugar control in type 2 diabetics, so you would not help your case by talking about weight loss, although that might happen, it also might not and is not a reason for them to prescribe the Rybelsus according to NICE guidelines, and also the use of Rybelsus for weight loss is off label.

The NHS is allowed to prescribe Wegovy (semaglutide) and Mounjaro (tirzepatide) for weight loss as far as I know, but it would be for people with a high BMI and with other co-morbidities, which rules many people out, and is subject to both the NICE and the local guidelines.

I was prescribed Rybelsus after requesting it at my GP practice on realising that I was on the placebo. Also pertinent to this is that I had tried Metformin and could not tolerate it, and that I would not be able to take any SGLT 2 inhibitor drugs as that would be the next line they would try, as I am on a low carb diet, and there can be a risk of DKA if you are low carb on SGLT2 inhibitor drugs. I was not prepared to up the carbs in my diet as the low carb approach was having a huge effect on both weight loss and bringing the blood sugar down.

I did the research and got ready to make my case with a list of reasons why I should be prescribed Rybelsus, but just looking at my results for blood sugar control (from my CGM) while I was on the run in and then the placebo was enough for them to prescribe the Rybelsus, and they are happy to carry on after my excellent HbA1c result this month after 3 months of the prescribed Rybelsus. See my signature for the results.

I have also lost weight, but this is mainly because of my low carb diet and exercise, and not really as much to do with the Rybelsus - the big effect the Rybelsus had was on my blood sugar, and in normalising my insulin response, and helping with the fatty liver.

It has been decided to keep me on the 7mg dose as this is working well to control the blood sugar numbers.

Thanks @AllieRainbow this is really interesting. I am also on a low carb diet and do loads of exercise…. For years this was enough to keep my HbA1c in the forties but then post menopause it started to creep up no matter how carefully I ate. So I have been on Metformin for a couple of years which I tolerate well, but I am not convinced it’s actually working for me. And the low carb diet is hard to stick to all the time! After just two weeks of 7mg oral semaglutide my BS is down from 7 to around 5.5 average daily. I don’t need to lose any weight although a few pounds would be nice, it’s just such a relief to eat how I normally do and for my BS to be back in normal range. If the side effects settle down I would rather be on Rybelsus but same dose as you, I wouldn’t cope with a higher dose although some trial participants have managed to argue their cases for the 7mg ongoing instead of 14mg. There’s a good article under boltpharmacy about why GPs are reluctant and/or unable to prescribe Rybelsus if Metformin is tolerated. Makes sense especially for non obese patients.

 

[AllieRainbow]

Thanks @AllieRainbow this is really interesting. I am also on a low carb diet and do loads of exercise…. For years this was enough to keep my HbA1c in the forties but then post menopause it started to creep up no matter how carefully I ate. So I have been on Metformin for a couple of years which I tolerate well, but I am not convinced it’s actually working for me. And the low carb diet is hard to stick to all the time! After just two weeks of 7mg oral semaglutide my BS is down from 7 to around 5.5 average daily. I don’t need to lose any weight although a few pounds would be nice, it’s just such a relief to eat how I normally do and for my BS to be back in normal range. If the side effects settle down I would rather be on Rybelsus but same dose as you, I wouldn’t cope with a higher dose which means I am probably going to give up the trial and see if GP will prescribe.

I wear a CGM and I have definitely seen my responses change so that they are more normal, so I think the Rybelsus is really doing a lot. The dawn phenomenom is going down now, and I am under 7.8mmol/L within 2 hours of eating almost 100% of the time, which is a normal response.

Looking at my graphs over the run in period and then during the placebo it seemed that it was working to get the blood sugar down (and then not working when I started the trial tablets and was on the placebo) - and then I ran a little experiment to see what the difference would be back on the real thing to confirm what I suspected.

I had about 3 weeks worth of tablets left from the run in period and it was very clear within the first few days of resuming the run in tablets that I had been on the placebo as my blood sugar started to go down straight away. I went back down around 3 mmol/L in just 2 weeks, from a daily average of 9.4mmol/L to 6.5mmol/L.

I had been unsure whether it really was the placebo or not, but this was very clear, and made my mind up about leaving the trial and seeing if I could get it prescribed as it was clearly making a big difference to the blood sugar numbers.

 

[AllieRainbow]

Thanks @AllieRainbow this is really interesting. I am also on a low carb diet and do loads of exercise…. For years this was enough to keep my HbA1c in the forties but then post menopause it started to creep up no matter how carefully I ate. So I have been on Metformin for a couple of years which I tolerate well, but I am not convinced it’s actually working for me. And the low carb diet is hard to stick to all the time! After just two weeks of 7mg oral semaglutide my BS is down from 7 to around 5.5 average daily. I don’t need to lose any weight although a few pounds would be nice, it’s just such a relief to eat how I normally do and for my BS to be back in normal range. If the side effects settle down I would rather be on Rybelsus but same dose as you, I wouldn’t cope with a higher dose which means I am probably going to give up the trial and see if GP will prescribe.

@MrsBezzer Just to note about what you said re leaving the trial so you could stay on 7mg - I know that people have asked to stay on the 7mg dose for the trial period due to side effects on the higher dose and also if they do not have much weight to lose and the Ascend people are OK with that - it could be worth you talking to them about your dosage if you do end up on the real stuff once you are past the run in and the trial starts.

 

[MrsBezzer]

@MrsBezzer Just to note about what you said re leaving the trial so you could stay on 7mg - I know that people have asked to stay on the 7mg dose for the trial period due to side effects on the higher dose and also if they do not have much weight to lose and the Ascend people are OK with that - it could be worth you talking to them about your dosage if you do end up on the real stuff once you are past the run in and the trial starts.

Yes, thanks @AllieRainbow I will wait and see what happens at randomisation. So far the worst side effect for me is the crippling bone achy fatigue which means some days I can barely do anything let alone lift weights and do all the other exercise that I aim to do to maintain muscle mass. And disturbed sleep which doesn’t help. Having recently retired to focus on my health and be less sedentary that’s quite ironic!! It’s all about finding the right balance. Thank you for your comments

 

[AllieRainbow]

Yes, thanks @AllieRainbow I will wait and see what happens at randomisation. So far the worst side effect for me is the crippling bone achy fatigue which means some days I can barely do anything let alone lift weights and do all the other exercise that I aim to do to maintain muscle mass. And disturbed sleep which doesn’t help. Having recently retired to focus on my health and be less sedentary that’s quite ironic!! It’s all about finding the right balance. Thank you for your comments

That sounds very hard to deal with. I had similar problems with blood pressure medication some years ago, which led to me having to stop taking it due to needing around 15+ hours sleep a day and still feeling exhausted.

 

[Mrs Redboots]

Just grumphing because my insides are playing silly******* again - either won't go or can't stop! And when they do both on the same day..... oh well.

Edited by mods to remove profanity

 

[MrsBezzer]

Eek, bad luck, hope things settle down again!

 

[Mrs Redboots]

Thanks. Better again today, but then I went and fell over - not badly, and landed in a pile of my husband's clean laundry - which shook me up, and although I've been out for a walk since then, I'm still a bit shaky!

 

[Heather Noller]

@MrsBezzer Just to note about what you said re leaving the trial so you could stay on 7mg - I know that people have asked to stay on the 7mg dose for the trial period due to side effects on the higher dose and also if they do not have much weight to lose and the Ascend people are OK with that - it could be worth you talking to them about your dosage if you do end up on the real stuff once you are past the run in and the trial starts.

I'm on 7mg as side effects on 14mg didn't settle (nausea) after 2 months. Rang up helpline and they suggested I return to 7mg. Weight loss not an issue for me as lost alot on Momenta NHS restricted calorie diet before semaglutide trial.

 

[ChrisMullins]

Starte

Sounds interesting but I’ve never heard of it? Would you be able to give more detail on what it is and what it entails or post a link about it? Think it would be helpful to other members to know more about it

d

Just thought aid start a discussion here for anyone on the Ascend Plus trial by Oxford University.

Started my “Run In” phase yesterday and so far so good. No side affects other than fatigue. How are other folks doing?

Started a while ago, lost weight from 103 to 85 kg, was on Himulin insulin, say was as I'm now off that, the last 3 HBA1C tests show below diabetic range but at risk of becoming diabetic.
So all good, only downside is the iffy stomach, I'm just really getting used to the tablet and stomach a lot better than it was.

After the lead in is the randomisation, you could end up with taking Smarties or the real tablet.
I must be on the real tablet with my progress to date.

 

[_snoopy]

I have recently started this trial on 1st of the "X" type yellow labelled containers.
As soon as I put the 1st tablet on my tongue (and the back of throat) it tasted horrible and bitter. Wasn't sure for a few days if I was on the Semaglutide 14mg or they had just added a nasty taste to the placebo. Had the burps & hiccups and a slight upset stomach. It has quickly become apparent to me that I am on the drug, as my waking fasting levels are now down to around the 5.0 mmol mark (down from 10 or 11mmol before I started the run-in 3mg tablets). I am keeping a watchful eye in case it goes below 4. My levels yesterday were: upon waking 5.1, before lunch 5.4, before dinner 4.7mmol. So far this is the lowest reading I have ever had since being diagnosed in 2004. May need to ask for the 7mg version. Next HbA1c is in late May for diabetic clinic in early June. Am also on a low dose of Gliclazide.

 

[Yellredder]

I started this in the autumn but came off when I went on the 7mg as it made me so unwell. Anyway have agreed to go back on it and see what happens.

 

[Aubrey3]

I started this in the autumn but came off when I went on the 7mg as it made me so unwell. Anyway have agreed to go back on it and see what happens.

Wishing you well with it this time around. There is denying that this is a challenging trial in the first few months. Try different eating patterns to minimise the discomfort. From my experience it is absoloutely imperative to ear much smaller meals than previously.

 

[Missmydoggies]

Hi. I'm about 2 weeks into the randomisation and convinced I am taking the placebo. Did anyone else notice a difference in the taste of their run-in drug compared with their randomisation drug? I found the actual semaglutide tablet that I took during the run-in was very bitter on my tongue when swallowing. The randomised drug I'm taking now has no such taste and is completely bland which is why I am sure it must be the placebo. What have other people experienced in regards to the taste?

I feel exactly the same, no taste to the randomised drug which I believe to be the placebo, in fact I actually sucked it and it was totally tasteless, you would think that the trial people would have known people would realise this, as you said the real thing was bitter and I felt a sort of fizzing as it went down, this can't be helping with the trial. My appetite has now come back with a vengeance and I have put weight back on that I lost.

 

[_snoopy]

I have recently started this trial on 1st of the "X" type yellow labelled containers.
As soon as I put the 1st tablet on my tongue (and the back of throat) it tasted horrible and bitter. Wasn't sure for a few days if I was on the Semaglutide 14mg or they had just added a nasty taste to the placebo. Had the burps & hiccups and a slight upset stomach. It has quickly become apparent to me that I am on the drug, as my waking fasting levels are now down to around the 5.0 mmol mark (down from 10 or 11mmol before I started the run-in 3mg tablets). I am keeping a watchful eye in case it goes below 4. My levels yesterday were: upon waking 5.1, before lunch 5.4, before dinner 4.7mmol. So far this is the lowest reading I have ever had since being diagnosed in 2004. May need to ask for the 7mg version. Next HbA1c is in late May for diabetic clinic in early June. Am also on a low dose of Gliclazide.

Update. Now on the 7mg dose (containers labelled "Y" type treatment).

 

[tioca]

Having been on the placebo for 2 months now, my Libre 2 sensor shows I've gone from 99% in range to 73%-80% in the last week or so. The graph of my readings was a nice straight line on the real meds but is now all over the place again - especially high in the mornings despite going back to low carb.

My request for NHS-prescribed Rybelsus was discussed at my GP's MDT today and the answer is no. When discussing this with them, after the meeting, the reasons they gave were all pretty much flawed and while they admitted that my corrections (including again showing them the data from my sensors before, during and after the real meds) had value, they won't review me for another 6 months. Even then, I have my doubts that I'll succeed. I'm in Cambridgeshire where they (even consultants) seem terrified of the local Medicines Policy people.

I feel I meet the criteria as I have many metabolic conditions and side effects that would benefit from Rybelsus (and I would need fewer meds eventually, no doubt), and I'm intolerant of all T2D meds I've tried other than metformin. And I got on so well with Rybelsus!!! It felt like a wonder drug that might solve many problems in one go, and reduce my interactions with the NHS. But they won't budge. It doesn't help that my time on the real meds took me from the obese category to overweight, or that my last HbA1C reading included a 2 month period when I was on the meds. They also said they don't believe that I'm on the placebo, despite all my data. They conceded afterwards that it certainly looked as if I was, but they said that without proof how can they tell?

For those of you who were able to get it prescribed on the NHS after you found you were on the placebo, are you in a different weight category to me? Did you go down a different path than I did (I spoke to the diabetes nurse + a GP) ?

I think I'll put my reasons for wanting it in writing (again) so maybe at the MDT in 6 month's time they'll get their facts straight. But unless I'm there, in the meeting, there's nothing to stop them getting the facts wrong again and then try to tell me that I'm wrong when I try to correct them. And, to tell the truth, I got the impression they're just not that keen on it.

To add, when I told them that others on the trial who are now on the placebo HAD been allowed to get it prescribed, a GP firmly said that that shouldn't have happened and it was wrong that people were writing about it on forums.

 

[EllieM]

Maybe I'm being dim here but would they have done better not to have a run in period but just put everyone on drug or placebo from day 1? If a drug is clearly working for someone and they find their results worsen after (possibly/probably) going on the placebo, they are bound to want to come off the trial and be prescribed the medication. But that distorts the results of the trial as you presumably need sufficient numbers to keep taking the placebo to validate the results...

Are there procedures in place for ending trials early for a "wonder drug" that is clearly working? Am guessing not, because you need the long term results for safety concerns....

Not on this trial myself, but I've been on a randomised trial where I didn't know if I was on placebo or not. The organisers were very keen to keep people taking the pills.

 

[AllieRainbow]

Having been on the placebo for 2 months now, my Libre 2 sensor shows I've gone from 99% in range to 73%-80% in the last week or so. The graph of my readings was a nice straight line on the real meds but is now all over the place again - especially high in the mornings despite going back to low carb.

My request for NHS-prescribed Rybelsus was discussed at my GP's MDT today and the answer is no. When discussing this with them, after the meeting, the reasons they gave were all pretty much flawed and while they admitted that my corrections (including again showing them the data from my sensors before, during and after the real meds) had value, they won't review me for another 6 months. Even then, I have my doubts that I'll succeed. I'm in Cambridgeshire where they (even consultants) seem terrified of the local Medicines Policy people.

I feel I meet the criteria as I have many metabolic conditions and side effects that would benefit from Rybelsus (and I would need fewer meds eventually, no doubt), and I'm intolerant of all T2D meds I've tried other than metformin. And I got on so well with Rybelsus!!! It felt like a wonder drug that might solve many problems in one go, and reduce my interactions with the NHS. But they won't budge. It doesn't help that my time on the real meds took me from the obese category to overweight, or that my last HbA1C reading included a 2 month period when I was on the meds. They also said they don't believe that I'm on the placebo, despite all my data. They conceded afterwards that it certainly looked as if I was, but they said that without proof how can they tell?

For those of you who were able to get it prescribed on the NHS after you found you were on the placebo, are you in a different weight category to me? Did you go down a different path than I did (I spoke to the diabetes nurse + a GP) ?

I think I'll put my reasons for wanting it in writing (again) so maybe at the MDT in 6 month's time they'll get their facts straight. But unless I'm there, in the meeting, there's nothing to stop them getting the facts wrong again and then try to tell me that I'm wrong when I try to correct them. And, to tell the truth, I got the impression they're just not that keen on it.

To add, when I told them that others on the trial who are now on the placebo HAD been allowed to get it prescribed, a GP firmly said that that shouldn't have happened and it was wrong that people were writing about it on forums.

As to their comment that people should not be writing about it on forums - I am pretty sure I have never had to sign an NDA to get medical treatment! This is my information and I can do what I want with it. As long as I am writing truthfully and honestly about my experience, and not giving out medical advice which I am not qualified to do, I see no issue there.

I was 34.3 BMI when I started the trial, 30.9 BMI when I had the meeting where I was prescribed the Rybelsus, and I am now 27.3 BMI. So I was obese, and I am now well into the overweight category. I expect to be normal BMI in around 12-14 weeks. Weight loss so far is from lifestyle changes, low carb, calorie deficit and a little perhaps from the Rybelsus (minimal input from the drug in my opinion, but the weight loss, and gain in muscle from exercise will definitely help to combat insulin resistance and reduce inflammation). I think the Rybelsus seems to make my response to food more like someone without diabetes and the dawn phenomenon definitely seems lower now than it was, so I think it has been very helpful for getting the numbers down over time, and clearly had an effect as demonstrated by the placebo results.

The meeting was with the clinical practitioner, not the GP, and I went from a HbA1c of 121 in Aucust, to 81 in September (low carb diet and lifestyle changes plus the run in, to HbA1c of 40 in February following continuing the lifestyle changes and low carb, plus the genuine drug from mid November. The clinical practitioner reviewed my results at that point (November) from my CGM and agreed that the Rybelsus had definitely being doing plenty and that it was also very clear that I was on the placebo as it was obvious from the CGM graphs and reports that the BG had started going upwards again with no changes to diet and lifestyle to account for that. I also had the issue of being unable to tolerate Metformin at all and being on a very low/low carb diet that had done so much to improve things that I did not want to go on any medication where I would need to increase my carb intake. There was also a good improvement in the liver results after starting the run in period (so being on the genuine drug).

My clinical practitioner is delighted with my progress. The dose is still 7mg as it did not need increasing due to the results of the first 3 months of prescribed drug from the GP surgery. I recognise that I am very lucky to have such a great surgery behind me, and hope that this continues to be the case in the future as they have made me feel supported in dealing with the diabetes.

 

[AllieRainbow]

Maybe I'm being dim here but would they have done better not to have a run in period but just put everyone on drug or placebo from day 1? If a drug is clearly working for someone and they find their results worsen after (possibly/probably) going on the placebo, they are bound to want to come off the trial and be prescribed the medication. But that distorts the results of the trial as you presumably need sufficient numbers to keep taking the placebo to validate the results...

Are there procedures in place for ending trials early for a "wonder drug" that is clearly working? Am guessing not, because you need the long term results for safety concerns....

Not on this trial myself, but I've been on a randomised trial where I didn't know if I was on placebo or not. The organisers were very keen to keep people taking the pills.

I think the issue here was that they needed to see if people would tolerate the drug as the dose starts off at 3mg, and then goes up to 7mg and then to 14mg for the trial period. Some people have really bad side effects and cannot tolerate ithe drug.

I suppose one way to do it without it being obvious could be to start at 3mg or a placebo and then up the dose for the real tablets on the same schedule, and then people would not be as sure about placebo or not as they wouldn't know they were on the real one for definite at the start as they do on the trial. Maybe there are some ethical considerations to do with dose changes? I don't know how drug trials work in any detail.

This trial is to do with looking at whether there are benefits for lessening incidents of cardiac and/or stroke events I think, rather than the efficacy of the drug for diabetes in terms of blood sugar control. They will have done earlier trials that were to do with the drug and its effect on improving diabetes control.

I remember feeling absolutely gutted once I realised it must be the placebo, when it was really working for me. I will still be filling in questionaires for the duration fo the trial although I withdrew from the trial once I realised it was the placebo from the CGM results over several weeks.