GLP1-RA - A pathway to Comprehensive Metabolic Care with Evidence - PES Midsummer Conference 2026

0:00 I'm consultant endocrinologist working at KMU hospital and research center. I welcome you all for this 12th midsupper uh Pakistan indocrine society conference. So this is basically the talk is on GLPs. Uh so for this uh we want to invite our chairpersons. Uh our first chairperson is uh professor Dr. Osma Malik. She is a consultant endocrinologist. Ma'am you have uh you can come on the stage. You have your seat. Our second panel of expert is professor Dr. Ah Shamir. He is a consultant indocrinologist. He will join us soon. And uh our third panel of expert is Dr.

0:46 Omar Yusf Raja I think. So he is he will also join us soon. So we have uh also uh Dr. Salee Gureshi if you can come on the stage to have your seat for the panel of experts and also we have another panel of expert that is Dr. Omar Wahab uh if he is there he can join us on the stage also and also we have a professor Dr. Say aher. So you can come on the stage sir to have your seat sir. So ladies and gentlemen you know that

1:33 obesity is a metabolic bomb. It is basically responsible for all the metabolic diseases like hypertension, diabetes, fatty liver all the stuff uh this due to the di this is due to the obesity. So the talk is about the GLP receptor agonist a pathway to the comprehensive metabolic care with the evidence. So for this we have a renowned speaker. He is also a leader in the endocrinology. He is a professor of endocrinology in Northwest General Hospital. I want to invite uh professor uh Dr. Arshad Dusen Sab. So you should come on the stage with a big clapping [applause] raim. Thank you very much. Thanks for all of

2:18 you to to all of you for coming here. So without any further delay, we'll start our talk. So uh before I actually present the actual slides of the study, I just want to give you a little background to the study as well. This is something quite well known to all of you that Pakistan has one of the biggest burden of diabetes and I think the this reservoir there are a lot of undiagnosed patient as well in pre-diabetic which in time to come will become diabetic and I think these are the recent statistic which I'm presenting here. So one in three adults in Pakistan previously used to be one in four now they say one in three every third adult actually in Pakistan is affected by diabetes. If you look at the uh the role of

3:06 simaglutide and GLP1s in this whole scenario. So what are the unmet needs? The unmet needs usually you know what we from the studies what we we know are you know one in four patient achieve target HVC of 7% or less and the adherence to the medication is a lot less is they say about 50%. Quality of life is also not good. more than 60% patients report poor quality of life due to fatigue, obesity and complication of diabetes. So where does the simaglutide fits in is on the right side as you can see. So the simoglutide provides you a therapeutic innovation you know in and giving you dual benefits like glucose control and weight control and by doing those two actually it lowers your CV events as

3:51 well. So it gives you the benefit of protection in in terms of cardiovascular events. Simaglutide well known to you is a human GLP1 analog 94% homology with a human GLP but what we are presenting today is slightly different so as we know the biological production which is the recominant DNA technology the simaglutide initially is a biological product which was the by the innovator and it's a very long and lengthy process you have to you know have a gene and then you know isolate it into a bacterial cell there are different you know parameters and different enzymes and this whole process of developing one biological molecule might take up to 5 years and in some cases up to 10 years.

4:37 However, if you look at the biosynthetic peptide production which is SPS that is actually solid phase peptide synthesis it's a stepwise chemical assembly in a controlled environment. So the process is usually very simple those amino acids then you know by different chemical reaction and different linker you actually add them up and then you there's a chemical process then you end up uh producing this biosynthetic peptide. How do you compare this with the recominant DNA? So the biologicals as you can see it needs extensive trials required for product approval. There has to be you know pre-clinical studies and then clinical then phase 1 2 and three studies for synthetic peptides biosimilarity studies are even not required only safety purity and potency what I have just uh you know underlined

5:23 here this is what is needed by FD and EMA that all you have to do is to prove us that it is safe is pure and potency then when we talk about lotto lot consistency because of the biological processes in the living cells there are chances that you know in the biological recumbent DNA they you know there may be some variation in lot to lot however in uh chemical synthesis you know it ensures identical active ingredients across all the lots then you talk about the host cell impurities that's what the mostly actually you know press you on these impurities so the risk of host cell impurities is there in biological however it is not there in the syn synthetic peptide because there are no host cells there so the risk of you know bacteria yeast and all those uh you know

6:10 impurities is actually none. Now what does the FDA say about the biosynthetic peptide? This was a question asked from us the last time we presented this study that you know what does the FDSA say? So anda is you know abbreviated new drug application for you know the newly purified synthetic peptide this is on their website as well. So biosynthetic peptide by FDA perspective they defined peptide as amino acid polymers with less 40 or less than 40 amino acid is actually called a peptide. So biosynthetic synthesite peptide can reference the recominant DNA origin you have to reference the innovator drug and the end pathway allowed in the same active ingredients. If you have the same active ingredient, then the pathway actually allows you to make one synthetic biosynthetic pep

6:58 peptide and [clears throat] comparable impurity profile you have to show that as well. And you have to demonstrate safety, purity and potency. And this applies to key peptide. What are other peptides which have been allowed before is actually glucagon, laglutide, uh, niceride, uh, terrapide and teloglutide. And the focus is basically on impurity control and imunological risk. And so to summarize this, the advantages of synthetic peptides are identical structure to the reference biological product, no risk of host cells related impurities and consistent product safety and efficacy. Now our study is a real world evidence. So I just want to highlight few um uh

7:44 facts about the real world evidence. So globally, 1200 studies have been done on GLP-1 analoges and different analoges including simaglutide and real world evidence is actually taken uh you know by FD and EMA for label expansion and HDA decisions. So even if the drug in initial trial have been done the later expansion the label expansion actually happens with the real world evidence. RCTs as you all know randomized control trial they are you know they're testing the efficacy under ideal condition. However, real world evidence is totally different. It measure the effectiveness in a real world patient, real patient, real coorbidities, adherence issues and socioeconomics constraints. In RCT, you have no soio economic constraints,

8:29 policy impact because you produce this evidence, it gives you a value based healthcare which I'll be showing you from our study as well. So you know it's very good for policy if you want to make policy and you know the key message is that the real world evidence transform medicine from evidence limited to evidence inclusive um evidence. Now bridging the evidence gap if you look at globally the clinical trial you know include only 2 to 3% of low middle- inome countries patients yet 85% of the world population lives in low middle uh low middle- inome countries. So in Pakistan 70% of the health spending is out of pocket as you all know. Uh ideally it should be the GDP is 0.4% of GDP but it should be more

9:17 than 6%. So the real world evidence help us in cost effectiveness and resource allocation clinical practice relevance. You'll be sitting in your in your clinic and you're seeing the real patients. You see the the adherence, the tolerability, patient reported outcomes in real setting and empowering local research. That's what we did as well the local research. So this is our study real world evidence and the effectiveness and safety of biosynthetic hemaglutide in type 2 diabetes which is a multic-enter study. These are the protocol which we got published a few months ago in Y and our studies also published and I think you'll be getting copies of the studies as well. So the study rationale the evidence gap as we know that you know uh limited real world evidences are there

10:02 on the efficacy medication adherence and quality of life on biosynthetic simaglutide in fact probably none this is probably the first study we are doing the study rationale was to bridge the evidence gap by uh evaluating the biosynthetic simaglutide in real world non-interventional and multic-enter study so the primary objective was actually glycemic control uh as a change in HV B1C and I'll be showing you the breakdown of the HB1C. We had a lot of secondary objectives. So one was actually to break down the HB1C into different whether we can get a very good control. Can we bring it up to 7%. So we have actually broken it down and also uh another was you know a drop of 1% of HB1C and also we were looking at the weight loss from 3 to 5% uh if

10:48 possible in these patient and then we had a composite outcome which was HB1C of more than 1% drop but at the same time a weight loss of 3%. And we also included quality of life and this is something different but we thought we should do this and then we I actually requested to add this medication adherence and uh you know this was very good you know for us to see because as reported 50% patient you know non-adherence to a medication. These are the ethical approvals. So we have national approvals. We actually got it from national bioeththics committee before we actually moved on to the different centers and international trial registration. We did this study uh uh with the University of S Malaysia and we got this trial registered in Australian New Zealand clinical trial registry and the number is there. So the

11:34 study it was a prospective openlel observational study 30e duration both male and female of more than 18 years and uh all patient with type 2 diabetes at least 12 weeks prior to inclusion if they were diagnosed with diabetes they could be included in it treatment initiation and switching from one drug to the other or adding more drug was actually at the discretion of the physician and the semiglutide was administered subcutaneously once weekly through the pre-filled injector Dose adjustment was again left to the the physician. It was a physician decision you know what dose they want their patient to be on and there were three study visits uh one uh baseline and then the 12 weeks and then at the end of the study and discontinuation of any drug or simaglutide was also left to

12:21 at the discretion of the um physician. This is the consort. As you can see, we had 437 patients screened, but only 309 assigned the consent to be enrolled in the study. Then there were further drop and uh we came down to 268. So the baseline assessment was completed by 268. When we did the 3 months follow-up, there was a further drop and it came down to 235. So 221 completed the study and the effective analysis was done on 217 because some of the patients had the missing data. And to show that yet it really represents the whole of the Pakistan we took centers all over the Pakistan including Azad Kashmir. So we had patient from you know the capital territory Islamabad the Omar Mahabh and

13:07 Omar Raja they were looking after that and u we had Punjab Sin Baluchasthan KPK and Kashmir. So before we go to preliminary results, if you look at the baseline characteristics, it's a very busy slide, but I've just you know um uh made those ones in bold, the BMI, if you look the baseline BMI was very high in our patient 33.71. Physical activity was very little people, you know, 104 people out of all this study were totally sedentary. And if you look at the comorbids, I have highlighted this for you that it's not that we took all the healthy patients, we took patients with the hypertension, dispidia and cardiovascular disease as well. the HB1C if you look on the right there on the top or baseline HB1C was 9.27 27.

13:53 If you look at the medication, so majority of the patient were on SLD2 inhibitors, which is very good to see that you know uh most physicians, you know, everyone is actually following the guidelines. So almost all patients you can say were on SL2 inhibitor a lot more on metformin, premix insulin, sulfanura, some of them DPP4, basil insulin and TCDs. Now how do you see the change in HB1C? If you look the trajectory here, so the orange color is a female and the male uh the blue is the male. And as you can see the change in the HB1C, the trajectory uh of course HB1C was slightly higher in in female initially to start with, but at the end they both achieved the goal of bringing down the HB1C. If you look at the bars, the first bar at the baseline, you see the purple color. So

14:39 81% patient actually had HBMC of more than 8% at the start. But if you look at the extreme right one, the yellow one you see, so 38% actually achieved HBNC of less than 7%. And then 37% actually achieved it between 7 to 7.9. And if you look at the change in the weight in 6 months time, uh as you can see the trajectory, there was a quite significant weight loss as well. And uh 76% as you can see that on the right extreme uh extreme right bar uh you see the blue color dark blue color 76.5% actually patients achieved 5% weight loss which was you know um quite significant. If you look at the subgroup analysis so we actually looked at whether patient characteristics or

15:25 diseases or disease degration affects the efficacy of the simaglutide. Does it have any effect on the efficacy? Uh so the answer is no. It was quite consistent in keeping it regardless of whether you were diabetic for 5 years, 10 years or you know more than 10 years, whether you were male or a female and whatever was your HB1C the results are quite consistent if you look at the age and gender and glycemic outcome just to further break it down. So again orange is the female and blue is males. As you can see less than 40 year I think female got you know very good control. they dropped their you know uh HB1C by 1.94 and as you go on and I think you can see a better effect but I think men actually got a little better after age 60 so they got a

16:10 little wiser so I think they got it controlled now if you look at the weight outcomes so the weight outcomes are more or less similar in in both of them but I think there was slightly more weight loss in females especially age more than 60 so BMI yes there was a drop in BMI of minus is 2.9. So whatever their baseline BMI was, you know, the average BMI we got we got it down to was minus 2.9. We also did the waist circumference ratio and you know so the waist actually dropped by - 6.7 cm which is quite significant. You see that there at the bottom there - 6.7 cm was a drop in the waist circumference. Now this part of the slide is busy so we'll just focus on the right side on

16:55 the bar. So this is the efficacy and conccommittant medication. So anyone who was taking simaglutide they were taking obviously other medication but these three were more significant. So sulfanylura those who were taking sophanalura had a drop of minus 1.87 those who were taking a metformin they actually had a drop up too and those on st2 they actually got minus 8 1.81 as well but we are not talking about beyond glycemic control alone. Beyond glycemic control there are other benefits as well. fasting plasma glucose as you can see there was a drop diastolic blood pressure there was significant drop in the systolic blood pressure as well if you look at the HDL there was a rise in HDL there was slight rise in LDL however the trial side there was a drop uh as

17:40 well coming to the medication adherence this was one of our favorite question so this um um u chart pie chart shows you that about 28% that's you know around about 30% was a low adherence to the medication and high adherence was only in 37.9 which is around about 40% people. So they took their medication whether simaglutide or other medication every day. Um and medium adherence is some of them actually missed the doses were about 33%. And again the on the right side is actually gender- wise distribution but we'll skip that one. We'll come to the more important slides. So now these are the targets we we achieved. So the bioshore study the

18:26 success rate. So on here on the left you can see these are the individual targets. So HB1CF less than seven about 38% patient actually achieved HB1CF less than seven. HB1C a drop of 1% was actually 73.3 which is quite significant. Whatever their baseline was they dropped it by one or even more than 1%. Weight loss of 5% was you know this was something we weren't expecting. So weight loss of 5% and about 93% and a weight loss of you know more than 10% was also reported in 6.9%. If you look on the right side the green one these are the composite that HB1C and the weight. So the first one is the HB1C without further weight gain HB1C of 7% that was 38% and those who were able

19:12 to drop HB1C to less than seven and also lose weight of 5% they were 36.9. We'll be comparing these figures with the other studies at the end. Then HB1C reduction of more than 1% and a weight loss of 5% was actually 70%. Which is very very significant. and the HB1C of less than seven without weight gain and without severe hypoglycemia the last one is 38 as well because whenever we talk about the drug we say efficacy and safety so we were looking at the safety as well which I'll be showing you the other slice but in the last one as you can see the you know there was without severe hypoglycemia 38.2 two. Now these are the patient reported outcome satisfaction and the hypoglycemia perception. So initially when we did the questionnaire at the

19:58 baseline the score was 16.5 it has a significant rise towards the end of the study to 29.6 the total score is 36 for quality of life and then the perceived frequency of hypo or hyper you know this was according to the patient that if they they were feeling having a hypoglycemia it dropped down from 8.5 to 5.2 into at the end of the study and this is patient well-being quality of life improvement over 6 months. If you focus on the right one there you see the dotted one that is when they started. So they had mental health issue they had you know emotional issues as well social isolation there were so many things but when you see it actually turned around and you can see physically functioning they are actually have a physical role as well and they were feeling a lot better. So this is based on the

20:43 questionnaire they have filled in intention to treat analysis. So there were significant clinical outcomes confirmed on this study and as you can see the HB1C drop was minus 1.65 and the weight reduction of minus 6.92. Now the intention to tal is a statistical method in which you actually put all the patient as they are regardless of whether they drop or they didn't drop whether they complete the study or did not complete the study. So it does dilute your results as such but it is to uh prevent the bias in the study. So the HB1C reduction I've already told you is minus 1.79 in our study. Now this bar is very complicated but the red is actually the you know perceived risk of

21:29 hypoglycemia. So the first one on here on the left that is at the start of the study regardless of what drugs they were on. So uh you know the score was quite high about 66% you know was the risk of hypoglycemia perceived hypoglycemia. The second bar which you see is actually the end of the study. So as you can see it dropped down to 16% from uh 60%. The rest of them are individually as per each drug but as you can expect with sulfanura and uh with uh insulin the risk of hypoglycemia is also very high. Now this is very important slide and I really want to take some time on this and I think people do ask and this was this is something not new. This is something which has been done before as well uh in the ABCD audit over years you know they actually looked at the end of

22:15 the stud not end of study but every 6 months to see has this simaglutide had any impact on the number of the pills or the insulin dose of the patient. So if you look on the here on the left on the first one SGLT2 inhibitor there was only a slight drop in this. Okay at the end of the study there was a slight drop in the number of the pills or the dose of the HTT2. If you look at the second one the green one is actually you know at the end of the study at the 6 months there was a rise in the role in the in the use of metformin in these patients but more significant is the premix incident. As you can see there was a 43% drop in use of premix insulin at the end of the study with the use of simaglutide. And the next one you see the sulfonalura it dropped down to 23%

23:00 and DPP4 by 88% and basil insulin dropped down to 88 quite significant drop and then the last one is the TCD it also dropped by 88%. So there was a significant drop in the number of the pills or the dosage and of the insulin and the oral medication. adverse events were really minor. There was not some much different from what the rest of the studies have reported. The most common was the GI one and uh only three patients actually stopped it because they they thought they were having more diarrhea so they stopped it. Pancreatic we don't know if this patient has had pancreatitis or not but it has raised MLAs and lipase and some epigastric pain. So we thought it's better to stop this drug. Retinopathy this patient actually has had retinopathy before. So obviously you

23:46 know his diabetic control was not good and um so it got worse. So that was the one stop but the rest of them were very minor um side effects. Now this is the health utility from the questionnaire. This is fivedimensional health utility score. We looked at it objectively what the patient has reported and on the bottom here this is when they started and that's where actually where they are. So it got improved. The next one is the patient reported outcomes that they thought at the start of the study how their quality of life is and at the end of the study how they perceived how good they are and you know how confident they are. Quality of life adjusted for years as quali. So simply one quali means one year free of disease and full of health.

24:33 That's just one year of quality life. So quali did we achieve any quali in this? So the answer is yes. If you look at the histogram there on on the left there's a dotted line here. So all the patients all patients are all on the right side of the dotted line. So that means yes they all of them got benefit and the central the the red line there is actually the mean of the all whatever they have got. So they got 0.10. So 0.10 10 in a year but we got it in 6 months and in in statistical terms that is quite significant improvement and quality of life. Now from economic point of view how do we translate the number of pills was also good but look at this one nim. So this is very interesting. Look at the

25:18 clinical effectiveness of daily dose insulin sparing. So we on the average reduce the dose of insulin by eight units a day. that translate to 240 units a month and at the end of the study 1446 that's equivalent to five pre-filled syringes uh sorry uh pens. So by 6 months this is what we achieved. We not only got the glycemic control we also lost weight as well we reduced the amount of insulin they were using and you know hence it was good for them economically as well. I think this is a little bit complex but anything on the right which you see is the one which is variable variance unfavorable variance that does not support pay from the pocket basically you know so willing to

26:03 pay is WTP let's if you're willing to pay on the left is what actually you see but this is very good from our perspective because you know from the dotted line we are on the left if you look at the biosynthetic simaglutide our cost was like say uh you know $8.99 6.96 there just under a million for a year okay is compared to the base of 1629 and same is the quality of life we achieved in other ones so from this study what we have learned that you know we got triple benefit from biosynthetic simaglutide we got reduction of HB1C of 1.82% we got a average weight loss of 8.4 Four, we got a drop in systolic blood pressure and diastolic blood pressure and also the metabolic targets. We got

26:50 lipid uh benefits as well and hence cardiovascular risk you know factor reduction and that's not all but if you see on the right side the enhanced quality of life was very important. So near doubling of treatment satisfaction as we said from 16 it went up to 29 and 18 point jump in patient related health. So the patient you know the the visual charts which we said those were reported by the patient that how confident they feel at the end of the study how good their control is if they lost weight the diabetic control was good they felt better and 0.39 improvement in health utility that was the the other parameter we checked so the bioshore study we can say a clinically safety we have shown you we have shown you the economic

27:36 impact of biosynthetic simaglutide and the high-risisk gly So when you talk about the safety high risk hypoglycemia and there was a drop from 66 to 16. So 76% relative reduction in high risk of hypoglycemia. But at the same time in the right side you see there were 14444 cumulative insulin units saved it not at the cost of poor control but at the cost of a good control good glycemic control and you know uh reduction in the amount of insulin and also there was a reduction in the conccommatant therapies as you saw in basil insulin premix insulin all of them. So let's compare our study with the reference study. So the first one is sustain one and the second one is the shore program. So shore was actually the same sustained study whereas a real

28:22 world evidence that was actually um uh the shore study. So if you look at on the the last one so our HB1C was 9.2. We compare this with the other ones. Our HB1C drop was more than the shore study minus one even better than uh the sustained study. Uh the weight loss was minus 8.4 and the patient satisfaction was much better as compared to those. These are the funding organization for our studies and these are the the investigators which took part in this study and uh that's the my last slide and thank you very much for listening to this. Thank you very much sir. Uh it was a

29:08 very nice presentation regarding the bioshore study regarding the GLP analogs. because of the short of time we will just only take comments from our respected chairpersons. >> After this uh excellent job by the lead investigator Dr. Asha Dusan there is little that I have to say but there are some points I have to make sub word of thanks to Ferosans especially Mr. Adnan and Mr. Dawa who uh in record time put this study together. It really is a pleasure to see all of you and so many old friends or young friends and thanks to FEL and the Pakistan endocrine society

29:56 endocrine society participants. I would be very interested in some comments from Najam Sab. It is difficult to keep track of uh Dr. Osama. I think now with these better glasses I can uh spot you otherwise you would have been a blur and I see server or objectives

30:44 synthetic drug. So we have to realize the context for the these are the first studies Pakistani real world data and this is not just extrapolation from the sustained trials efficacy and a very smart I never could you know imagine he can be so smart efficacy safety uh again thanks to Dr. Musarat because her center was one of the uh centers you know sub number of patients to this study. Now the two points I want to make is in adherence and persistence this is

31:32 where the Pakistani data is differing from the ozumpic trials settings discontinuation Pakistan that is not only because of the biological or the GI effects of whatever constipation diarrhea hiccups gastritis etc but it has also been the cost and then the early titration difficulties. trial mean to achieve 1 m dose which is slightly longer than the uh trials

32:17 71% 1 mig first 2 3 months of these GLP therapies These are the most important isra we can through slow titration or whatever way through you know giving some prokinetic drugs etc. >> Sir we have short of time if you can simplify. >> I'll just sum it up. Uh so this does not prove formal bioaclins to aumpic nor cardiovascular outcome like routine Pakistani practice may prove glycemic weight tolerability and signals are similar to the established uh

33:03 semaglutide therapy. Thank you. >> [clears throat] >> Thank you for an emergency replacement instead of air. So just just few things I know about this study. The first thing is that it's really a good thing to see that our national companies are coming up with the real world data and I must congratulate the ferros and all the team that they come with the idea that there should be a local data that we should have trust on it. We always talk about the international data and the different population groups. Then congratulations the whole of the team the all the colleagues that they they compiled the data and presented it very well. So I

33:48 think so Dr. Salem has really elaborated that this is one of the drug that now it frequently used very efficacious and really it's not only beneficial for the one just to control the diabetes but has got multiple effects. So I think the main main thing which we were previously lacking was the cost. Thank you very much and conclusion again. Thank you.

34:36 >> Okay. Thank you very much Dr. Arshad for such an elaborative talk on your study of bioshore. uh uh one thing I can uh what I interpreted from your u data that you have presented that uh the standard fall of HB1C which the international guidelines show is around 1.3% with sema glutide but your study in your study it showed that it fall up to 1.7% which is over and above the uh national uh international set standard so it's something very good the second thing is okay this drug was given over and above to DP PPP4 inhibitors in this study as well which which showed that it might have augmented the effect of DPP4 inhibitors as well because I have seen

35:22 some people stopping the DPP4 inhibitors and then starting these GLP-1 analoges and your study showed that you can give it and it might be one of the reason that HBA1C fall to such an extent. Number third is that it is an uh in the last slide which showed that it was an observational study. So um a better evidence can be obtained if you can go ahead with the bioshore uh study which include randomized control trial uh uh in order to generate a high level of evidence as well. And um uh one thing I was uh uh the uh these are some question because I have gone to the study just now that uh uh what were the parameters of recruiting the study whether the

36:09 patient who developed retinopathy was having uh retinopathy previously or he developed retinopathy dnovo while he was on the semaglutide and if we plan this randomized control trial in the form of randomized control trial then we can introduce these confounders as well. Uh very well presented study. Thank you very much. >> Thank you very much ma'am. Uh just just to guide you about the today's program I want to clear you that at 6:53 to 7:15 there will be inauguration of the pharma industry uh exhibition. After that 7:15 to 7:30 will be the MRI prayer pract and all of you are requested to be here at 7:30. So now I want to invite all the faculty, the chairpersons, the speakers,

36:56 the organizers and all the audience uh for the inauguration of the industry simple exhibition. Thank you very much.