| Title |
Assessing Bladder Cancer Risk in Type 2 Diabetes Clinical Trials: the Dapagliflozin Drug Development Program as a ‘Case Study’
|
|---|---|
| Published in |
Diabetes Therapy, September 2015
|
| DOI | 10.1007/s13300-015-0128-9 |
| Pubmed ID | |
| Authors |
Agata Ptaszynska, Samuel M. Cohen, Edward M. Messing, Timothy P. Reilly, Eva Johnsson, Kristina Johnsson |
| Abstract |
Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, decreases plasma glucose levels by suppressing renal glucose reabsorption and increasing urinary glucose excretion. Previously published pre-clinical data suggest that dapagliflozin lacks carcinogenic potential. This article reviews data on bladder cancer with dapagliflozin to illustrate the challenges in assessing bladder cancer in drug development programs in patients with type 2 diabetes mellitus (T2DM). Clinical cases of bladder cancer were analyzed in a pooled population of >9000 patients in 21 phase 2b/3 dapagliflozin clinical trials of up to 208 weeks' duration. In the 21-study pool, demographic and baseline characteristics were generally consistent between dapagliflozin and comparator groups. The overall incidence of malignancies was also balanced between the treatment groups, with an incidence rate ratio (IRR) of 1.035 [95% confidence interval (CI): 0.724, 1.481]. Nine of 5936 dapagliflozin-treated patients and 1 of 3403 comparator-treated patients reported bladder cancer, with an IRR of 5.168 (95% CI: 0.677, 233.55). All of these patients had clinical attributes typical of bladder cancer in the general population (≥60-year-old males; 8 of the 10 patients were current/former smokers). All cases of bladder cancer were reported within 2 years of starting study treatment. There was an absence of detailed workup of hematuria prior to randomization, and no hematuria workup data were collected proactively in the dapagliflozin trials, which is typical of clinical practice. Failure to exclude bladder cancer prior to randomization increases the chance of recruiting patients with pre-existing bladder cancer in clinical trials and may delay the final diagnosis. Of the nine dapagliflozin-treated patients with bladder cancer, eight had microscopic hematuria prior to start of treatment or within 6 months of initiating study treatment. The assessment of bladder cancer data illustrates the challenges of characterizing cancer risk in T2DM drug development programs. The totality of evidence to date does not suggest a causal relationship between dapagliflozin and bladder cancer. AstraZeneca. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 50% |
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 57 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 57 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 9 | 16% |
| Other | 6 | 11% |
| Researcher | 6 | 11% |
| Student > Master | 6 | 11% |
| Student > Bachelor | 3 | 5% |
| Other | 11 | 19% |
| Unknown | 16 | 28% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 24 | 42% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 12% |
| Biochemistry, Genetics and Molecular Biology | 1 | 2% |
| Unspecified | 1 | 2% |
| Nursing and Health Professions | 1 | 2% |
| Other | 3 | 5% |
| Unknown | 20 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 June 2022.
All research outputs
#14,159,409
of 22,691,736 outputs
Outputs from Diabetes Therapy
#442
of 1,008 outputs
Outputs of similar age
#137,996
of 266,664 outputs
Outputs of similar age from Diabetes Therapy
#11
of 15 outputs
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