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Medicine Matters diabetes

The reason for insulin degludec is because it's a new generation of basal insulin and we don't have many options you know as you think of the best the safest insulin that could be used was basal insulin we have to consider either the degludec, which is on the market since a longer time or Toujeo not the glargine-300, so at the time the study was designed the aim was to compare tirzepatide with the newer or newest generation of basal insulin characterized by the lowest risk of hypoglycemia so at the time that the study was designed degludec was actually more on the market than glargine-300 and this is why the choice was for degludec and as you probably know the study is a study comparing tirzepatide with degludec that is titrated according to how the deck is titrated in the clinical trials in which it was used and so we definitely were trying to use as a comparator, basal insulin with the lowest risk of hypoglycemia but at the same time used you know at the maximum extent possible.



 All three doses of tirzepatide were able to reduce HbA1c from baseline to a greater extent as compared to insulin degludec, and so they were all more efficacious in reducing the-- correcting hypoglycemia which was the primary endpoint of the study, as a consequence there were also more patients treated with all three doses of tirzepatide that achieved an HbA1c target lower than 7% or equal or lower than 6.5%, and I would also mention that there were significant proportions of patients with all three doses that achieved an HbA1c level lower than 5.7%, which is the upper limit of the normal range for HbA1c, meaning that these patients were actually receiving a treatment able to bring them back to normoglycemia.



And, in addition, I would also like to mention not unexpectedly that the body weight was reduced with the three doses of tirzepatide in a fairly dose-related fashion with the reductions ranging from 7 to 13 kilograms from baseline and obviously with degludec, especially because it was intensively titrated, there was an increase in body weight the patient's range gained on average about two kilos, so completely different trajectories in terms of body weight changes another advantage of tirzepatide over insulin degludec is again as expected the lower rate of hypoglycemia because tirzepatide does not cause hypoglycemia per se and therefore the occurrence of this side effect was lower as compared with the insulin degludec, which on the contrary causes hypoglycemia to a significant extent the only-- I would say-- issue with tirzepatide, which is something that we of course see very consistently also with the GLP-1 receptor agonists, is the occurrence of side effects, including nausea, diarrhea and vomiting and this was again occurring in a dose-related manner with the three doses of tirzepatide and to a higher extent as compared with insulin degludec, however, these gastrointestinal side effects were in most cases mild-to-moderate in intensity, only few severe cases of nausea for example were noted and they tended to occur very early after initiation of the treatment such that very few patients you know after week 20-24-- I would say had these kind of gastrointestinal side effects so they were largely located in the early phase of the study.



So I think that of course at the end of the day we are comparing two injectable therapies that have a very different profile in terms of glucose control, body weight changes, and risk of hypoglycemia, and also tolerability and this I think should in in some way make the therapeutic algorithm consider tirzepatide as probably the first injectable drug to be used in type 2 diabetes when oral agents are not sufficiently-- are not sufficient to control hypoglycemia