Table 3.

Summaries of bladder cancer cases

Study/age/gender/country	T/t group	Study day for bladder cancer diagnosis	Histologyb	Smoking, other risk factors	Hematuria		Reason for bladder cancer workup	Additional clinical information
					Within 6 months prior to rand.	After rand.
NCT00972244 [54]/75/male/Japan	DAPA 2.5 mg	43	Type: class 4 malignant cells TNM classification: T2N0MX Grade: 2	20 cigs/day for 50 years, stopped 2007	Yes	Yes	AE ‘occult blood positive’ on day 36	Continued positive urine occult blood since day 215; hematuria × 6 in 1.5 months; symptoms of anorexia and weight loss; metastases to the lung at diagnosis
NCT01031680/48/male/United States	DAPA 10 mg + MET + SU	74	Type: urothelial Grade: low	20 cigs/day for 34 years, stopped 2008 Hematuria and renal stones reported in 2008	Yes	No	Hospitalized for coronary artery disease; CT scan showed possibility of lesion in bladder	History of hematuria and renal stones ~2 years prior to randomization
NCT00683878 [55]/67/male/Argentina	DAPA 5 mg + PIO	144	Type: urothelial cell with areas of squamous differentiation TNM classification: T2 Grade: 3	Family h/o of bladder cancer PIO 45 mg used on day −223 to −16 AE of UTI reported on day 84	Yes	Yes	AE ‘hematuria’ on day 130 and AE ‘urinary bladder polyp’ on day 144	Trace blood in urine on day 1; multiple positive urines for blood; UTI on day 84. Gross hematuria on day 130. Urinary urgency and frequency prior to day 144; 80 × 60 mm mass at diagnosis
NCT01031680/55/male/Taiwan	DAPA 10 mg + MET + SU	169	Type: urothelial cell Grade: 1	Current smoker—5 cigs/day for 36 years	Yes	Yes	Intermittent hematuria for 3 months and persistent hematospermia	Trace blood on day 36 and day 1 Trace + blood in urine in 5 of 8 tests during the study
NCT00673231 [56]/63/male/Austria	DAPA 5 mg + INS	358 (AE of bladder neoplasm) 393 (SAE of bladder cancer)	Type: G2 TNM classification: pTa Grade: unknown	Current smoker—40 cigs/day for 50 years	No	Yes	Recurring microscopic hematuria since ~day 165 (according to the investigator)	Microscopic hematuria noted on day 165
NCT00673231 [56]/67/male/Hungary	DAPA 10 mg + INS	399	Type: urothelial cell Grade: 2	Never smoked	Yes	Yes	AE ‘hematuria’ on study day 372	Hematuria 1+ on day 13; 3+ on day 1; 7 of 9 urines positive for blood in study months 1–12
NCT00528879 [57]/60/male/Canada	DAPA 5 mg + MET	512	Type: urothelial cell TNM classification: pTa, pN0, M0 Grade: low	25 cigs/day for 25 years, stopped 1989	Yes	Yes	AE ‘calculus ureteric’ on day 509	Hematuria 2+ on day 15, trace hematuria on day 34
NCT00673231 [56]/66/male/United States	DAPA 10 mg + INS	581	Type: urothelial Grade: low	30 cigs/day for 42 years, stopped 2001	No	Yes	AE ‘hematuria’ on day 577	Hematuria on days 56, 84, 118 and 377 prior to diagnostic evaluation
NCT00660907 [58]/76/male/Germany	DAPA 10 mga + MET	727	Type: urothelial with partial squamous cell differentiation TNM classification: pT1, M0 Grade: high (G3)	20 packs, stopped 1980	No	Yes	AE ‘benign prostatic hyperplasia’ on day 727	Urine blood 3+ on day 726 Eleven prior urines negative for blood
NCT01042977 [59]/66/male/Canada	Placebo + INS + MET	136	Type: urothelial Grade: high	20 cigs/day for 50 years; cystitis reported as AE on day 32	Yes	Yes	Painless macroscopic hematuria for a few weeks	History of hematuria and positive dipstick results for blood in urine before and at randomization

AE adverse event, cigs cigarettes, DAPA dapagliflozin, INS insulin, MET metformin, PIO pioglitazone, SAE serious adverse event, SU sulfonylurea, TNM tumor, node, metastasis

^aThe dapagliflozin dose for this patient was up-titrated from 2.5 to 5 to 10 mg. At the time of event, the dose was 10 mg

^bCurrent accepted terminology is urothelial cell carcinoma, although transitional cell carcinoma is still commonly used. These are different names for the same malignancy