The Food and Drug Administration (FDA) has now approved Wegovy for diabetes (semaglutide), previously allowed for diabetes, weight loss. I wonder why? I was a consumer adviser on the FDA Advisory Board who voted in favor of Wegovy (semaglutide) diabetes. I reluctantly voted for it’s only because the drug slightly improved the lives of people with diabetes.

Small weight loss is one of the advantages of Wegovy. Patients given Vegovi in ​​clinical trials lost 5-10 pounds. It is useful for people with type 2 diabetes, but for ordinary people it is insignificant. The: average weight American men are 199 pounds, women – 171 pounds. Experts tell me that weight loss, even if small, can improve the health of people with diabetes. But for everyone else, what’s the difference between 199 և 189 or 171 և 166 pounds?

The side effects of Wegovy are horrible և I think the benefits of taking a drug for weight loss will outweigh the benefits. My blog և thoughts on when the FDA approved Wegovy in 2017 for diabetes. I have even more worries now.

(2017) Trace indications for a new diabetes drug

Last week, I sat on the FDA board as the sole consumer representative to consider voting for Novo Nordisk’s diabetes drug semaglutide. This is a new entry in the category of GLP-1 agonists, six of which have already been approved for use in diabetes.

The advantages are clear and strong. Semaglutide lowers glucose levels and helps patients lose weight [what I thought at the time was] significant level – an average of five to 10 pounds. Glucose lowering is a replacement measure used by the FDA to measure the benefits of new diabetes medications. The FDA allows substitute markers because it will take decades to prove or disprove that the drug prolongs or improves the life of diabetics.

However, the side effects are quite bad. At least 20% of the test participants had to drop out of school because they could not cope with nausea, diarrhea and constipation. (This is also a problem for other GLP-1 agonists.) These symptoms can lead to the use of side effects medications. At least one doctor on the panel raised the obvious. With so much stomach upset, it is not surprising that patients have lost weight.

This is the main killer of people with diabetes CVD: (cardiovascular disease). The FDA is closely monitoring the effects of any diabetes medication that may affect CVD. That’s why, in addition to five other clinical trials, Novo Nordisk conducted a two-year trial called SUSTAIN 6, which focused on CVD for secondary retinopathy of diabetic retinopathy, a problem that blinds half of all diabetics.

SUSTAIN 6 had mixed results. Fortunately, it showed a significant reduction in most CVD measurements. Compared with placebo-like drugs, those taking semaglutide had significantly lower mortality rates (myocardial infarction or myocardial infarction), non-fatal stroke, rheumatology (surgery needed to bypass or other coronary heart disease), or hospitalization. Unstable angina (poor blood flow to the heart).

Unfortunately, the data showed that semaglutide slightly increased the risk of hospitalization due to heart failure and had approximately the same risk (compared to placebo) of cardiac death. Deaths from all causes were approximately the same as in the case of placebo. The decline in the balance sheet was significant and the increase was small.

Of concern was the fact that diabetic retinitis showed a marked increase in the number of semaglutide users compared with placebo. In tests of other GLP-1 agonist drugs, the same pattern was shown և called “Early deterioration”. Over a period of three to four years, the rapid onset slowed, and soon the symptoms of placebo retinitis increased better than the group of drugs tested. However, Novo Nordisk did not continue the test to prove or disprove that this drug, semaglutide, would follow suit. In addition, the quality of research on retinopathy was poor. Preferred retinopathy tests were not performed, and data collection was inadequate. We can hope, but we can not assume that the rapid growth of seminoglutid-induced retinopathy will be smooth. Therefore, the panel doctors agreed that the rapid progression of retinitis is a real possibility.

The panel’s ophthalmologists discussed և assured us that there are many procedures for doctors to slow down the retina և, in their opinion, it is a manageable problem. Everyone agreed that people with diabetes were more concerned about the risk of CV, where semaglutide was clearly beneficial.

I had to leave the above problems to the experts. These doctors have been trained in medical research and statistics. However, I know that the population on which the drug is being tested should be reasonably compared to the population that is likely to use the drug. Diabetes is much more prevalent in the non-Hispanic Hispanic population. However, 80% of the participants in the trial were white (except for two trials in tri aponia).

The appropriate patient population is as important as the correct dose և time. I was the first participant to raise this issue, և only one doctor added his concern to mine. He abstained from voting yes or no. I wish I had thought of abstaining as an option. I voted yes, but I continue to be very concerned. Here are my remarks to the committee (light for editing, edited).

“Semaglutide really shows a decrease in glycemic level և body weight. It does not seem to cause hypoglycemia as often as comparative drugs [the drugs to which semaglutide was tested against]”The committee convinced me that retinopathy was manageable, that the absence of CV damage was of greater benefit. It has significant side effects: adverse events that cause a large percentage of patients to stop taking the drug.

“I am concerned about the lack of analysis of the racial-ethnic composition of the participants in the trial. Non-Hispanic people have the second highest rate of diabetes, but are so underrepresented in these trials that real black patients are in their lower 100s.

“I am concerned about the lack of a significant analysis of this subgroup as well. With such small specimens, it is impossible to know whether it has a different effect of ‘safety among women or ethnic groups’.

“Given the generality of retinopathy with diabetes, it is surprising to me that the study was not conducted in a standardized manner, which makes it not the best quality. The applicant seems to be dependent on other studies of other medicinal products to conclude that the “early exacerbation” of retinopathy shown in their trials is temporary և will ultimately benefit the patient. If semaglutide followed the example of other diabetes medicines, continuing the study for just one year would confirm the similarity of other medicines. As it turns out, the study stopped two years later, which does not allow any confirmation of profit.

“The trial was overwhelmingly white,” he said. Cardiovascular diseases are the number one killer of women, it is very high in the list of causes of mortal death. Diabetes is more common in black people, Hispanics, they are not well represented.

“History has shown that drugs tested on only one ethnic group or one sex can sometimes have a surprisingly harmful effect on subgroups.

“I am concerned about the lack of ability to analyze the subgroup. I will feel very bad if we do not continue to state that there should be more participants in the trial,: the trial should reflect people who need drugs.

“I strongly recommend further research with better demographics, which allows subgroup analysis to determine the effectiveness of blacks, Hispanics, women, and so on.

“We also need further follow-up to learn about the long-term effects of retinopathy.

“I think these additional studies should be required, as the public has a right to receive complete information about security.”