Stop-niddm trial

This population had the following characteristics: the mean age was Screening of a high-risk population yields one eligible subject per every 10 volunteers screened. This study should definitely answer the question of whether acarbose can prevent or delay the progression of IGT to type 2 diabetes mellitus.

Sign In or Create an Account. Advanced Search. User Tools. Sign In. Skip Nav Destination Article Navigation. Close mobile search navigation Article navigation. Volume 21, Issue Previous Article Next Article. Article Navigation. Emerging Treatments and Technologies October 01 This Site. Google Scholar. The primary endpoint was development of diabetes on the basis of a yearly oral glucose tolerance test OGTT.

Analyses were by intention to treat. Findings: We randomly allocated patients with impaired glucose tolerance to acarbose and to placebo. The STOP-NIDDM Trial has shown that acarbose treatment in subjects with impaired glucose tolerance is associated with a significant risk reduction in the development of diabetes, hypertension and cardiovascular complications. The aim of this paper is to present data and explanations refuting these allegations.

Blinding and randomisation were carried out by an independent biostatistician. Of the study population, 9. The changes in weight are consistent in different publications and are related to different times of follow-up and assessment.

The cardiovascular endpoints were a clearly designated assessment in the original protocol, and only those defined in the protocol and ascertained by the independent Cardiovascular Event Adjudication Committee were used in the analysis. Hypertension was defined according to the most recent diagnostic criteria.

The investigators stand strongly behind these results demonstrating that acarbose treatment is associated with a delay in the development of diabetes, hypertension and cardiovascular complications in a high-risk population with IGT.

The rationale for the use of acarbose was based on our understanding of the pathophysiology of Type 2 diabetes [ 3 ] and on a preliminary study showing that treatment of IGT subjects with the drug is associated with a significant reduction in insulin resistance as well as a decrease in postprandial hyperglycaemia and hyperinsulinaemia [ 4 ]. The use of acarbose was also supported by the observation that postprandial hyperglycaemia is a strong independent predictor for the development of Type 2 diabetes and cardiovascular disease [ 5 , 6 , 7 ].

Kaiser and Sawicki have recently published a paper in Diabetologia [ 8 ] in which they accuse the investigators of the STOP-NIDDM Trial of major biases in the conduct of the study, of manipulating the data and of conflict of interest. Here, the investigators would like to respond to the issues raised by Kaiser and Sawicki and to show that their criticisms are unfounded and flawed by misinterpretations, biases and inappropriate valued judgements.

Altogether, subjects were randomised into the study. As the data were obtained, quality control was applied and any incomplete or inadequate data were faxed back to the site for completion or with queries. Furthermore, no post-randomisation glucose data could be collected for 44 subjects: 14 of these withdrew their consent and the others failed to attend subsequent visits. Nevertheless, the reviewers and editorial staff of JAMA, following their rigorous reviews, insisted that we used the term.

This term usually refers to patients involved in a study who terminate their participation prematurely. No subject in our study was excluded from the modified intent-to-treat analysis for that reason. Most of the numbers are different from those given by Kaiser and Sawicki, and it is not obvious to us how they arrived at their values.

Randomisation was carried out by W. Randomisation was done in blocks of 4 and 6 to minimise the chance that the investigators could guess the treatment assignment. Numbered drug containers were used to implement the random allocation process. In other words, the numbered containers were assigned to each enrolled subject in consecutive order. Since blinding was carried out by an independent biostatistician, the sponsor of the study Bayer was also blinded to treatment.

Insinuating that they manipulated the data is a major unfounded accusation, which is surprising, unworthy and unexpected from any credible scientific investigator. At visit 3, subjects will be uptitrated to placebo or active drug mg TID for the rest of the study. By using titration, subjects are expected to increase their tolerance to the study drug.

Therefore, in contrast to what is suggested by Kaiser and Sawicki, both placebo and acarbose identical in shape, size and colour were titrated. Since this was a double-blind, placebo-controlled study, it is clear that the placebo was explicitly included. As opposed to Kaiser and Sawicki, we fail to see any contradiction in any of these official publications where dose titration is consistent with the protocol.

Again, Kaiser and Sawicki are making an inappropriate valued judgement when they raise the issue of conflict of interest due to the fact that some Bayer employees were members of the Steering Committee. The committee was composed of the principal investigator J.

Chiasson and representatives of the five regions involved in this international study: R. Josse from Canada, M.

Hanefeld from Germany, M. Laakso from Scandinavia, A. Karasik from Israel and R. Gomis from Spain. Since the infrastructure for monitoring and data collection was provided by Bayer, it was normal to have a representative from the company in each region. Throughout the course of the study, the Bayer representatives changed.

Since the research budget had to be adjusted over time, it was necessary to have some Bayer people around the table. However, all of these people were non-voting members, and all decisions and amendments were decided upon by the investigators only.

Furthermore, it is common practice to have company employees on the Steering Committee of major clinical trials. In fact, the preliminary study published in Diabetes Care in [ 4 ] was done to get on the Diabetes Prevention Program, since we knew that the National Institutes of Health would be calling for sites.

When they did, however, they decided that they would not include any site from outside the USA [ 12 ]. Two of the Canadian investigators J.

Chiasson and R. Josse then went to Germany to propose the project to Bayer. Furthermore, the data analysis, the statistical analysis and the writing of the manuscripts were the sole responsibility of the investigators.

Bayer played no role in these aspects of the study. The interim analyses were carried out by W. The final statistical analysis was contracted out to an independent biostatistician G. The new diagnostic criteria decreased the FPG cut-off point to 7. As it happened, 9. Kaiser and Sawicki suggest that we report different weight change in different publications 0.

Both numbers are correct. In the Lancet paper, we report the mean weight change over the whole study period which varied from 3 to 5 years depending on the patient. In the JAMA publication, the mean change over 3 years is reported. This suggests that some of the patients started gaining weight after 3 years and others stopped gaining weight after 3 years.

This is mentioned in the Lancet paper [ 1 ]. The nutritional evaluation data based on 3-day nutritional diaries have not yet been analysed. However, similar nutritional evaluations carried out in diabetic subjects on acarbose did not show any change in dietary habit in patients on acarbose [ 14 , 15 ]. In contrast to what is insinuated by Kaiser and Sawicki, the cardiovascular endpoints were all listed and defined in the original protocol dated March 14 , page 47, item As such, the cardiovascular endpoints in the JAMA paper were all clearly listed and defined [ 2 ].

The blinded committee retained 47 subjects in whom one or more cardiovascular events were confirmed according to these rigid criteria. Kaiser and Sawicki confuse the cardiovascular endpoints that were predefined in the protocol with the adverse events reported by the investigators.