Efficacy and safety of ertugliflozin across racial groups in patients with type 2 diabetes mellitus

Figures & data

Table 1. Phase III VERTIS clinical studies included in the pooled analyses.

VERTIS study name	MONO^9	MET^10	SITA2^13	SU^15	SITA^12	FACTORIAL^11	RENAL^14
NCT	NCT01958671	NCT02033889	NCT02036515	NCT01999218	NCT02226003	NCT02099110	NCT01986855
HbA1c inclusion criterion (inclusive)	7.0–10.5%	7.0–10.5%	7.0–10.5%	7.0–9.0%	8.0–10.5%	7.5–11.0%	7.0–10.5%
Background therapy	Diet and exercise	Metformin	Metformin and sitagliptin	Metformin	Diet and exercise	Metformin	Diet/exercise with or without AHA^a
Ertugliflozin treatment groups	E5	E5	E5	E5	E5/S100	E5	E5
						E5/S100
	E15	E15	E15	E15	E15/S100	E15	E15
						E15/S100
Comparator	Placebo	Placebo	Placebo	Glimepiride	Placebo	Sitagliptin	Placebo

Adapted from Figure 1 in Liu et al.³⁰

^aAHA monotherapy or combination therapy, including insulin and/or sulfonylureas.

Grey shading indicates the three placebo-controlled studies included in the placebo pool for efficacy analyses; all seven studies included in the broad pool for safety analyses.

Abbreviations. AHA, Antihyperglycemic agent; E5, Ertugliflozin 5 mg; E15, Ertugliflozin 15 mg; HbA1c, Glycated hemoglobin; NCT, ClinicalTrials.gov identifier; S100, Sitagliptin 100 mg.

Table 2. Baseline demographics and disease characteristics of patients included in the pooled efficacy (placebo pool) and safety analyses (broad pool).

Placebo pool: race/treatment (n)
	White			Black			Asian			Other
	PBO (378)	ERTU 5 mg (382)	ERTU 15 mg (374)	PBO (31)	ERTU 5 mg (34)	ERTU 15 mg (37)	PBO (79)	ERTU 5 mg (77)	ERTU 15 mg (77)	PBO (27)	ERTU 5 mg (26)	ERTU 15 mg (22)
Age, yrs	57.1 (9.6)	57.7 (9.2)	57.7 (9.7)	57.7 (8.9)	58.0 (8.0)	56.4 (11.0)	56.4 (10.1)	56.7 (11.5)	58.1 (9.2)	54.4 (8.6)	55.4 (10.6)	55.6 (9.9)
Male, n (%)	222 (58.7)	206 (53.9)	204 (54.5)	6 (19.4)	9 (26.5)	14 (37.8)	42 (53.2)	43 (55.8)	41 (53.2)	10 (37.0)	9 (34.6)	6 (27.3)
Body weight, kg	92.0 (20.8)	92.4 (19.9)	89.6 (17.4)	86.8 (23.0)	86.0 (16.9)	94.3 (22.1)	72.7 (15.7)	71.9 (16.0)	75.7 (14.8)	77.8 (14.5)	82.7 (24.3)	76.0 (10.3)
BMI, kg/m^2	32.2 (5.9)	32.6 (5.8)	32.0 (5.3)	32.7 (6.0)	32.0 (5.1)	34.4 (6.0)	27.1 (5.3)	26.8 (4.7)	27.9 (3.9)	29.4 (4.9)	31.6 (6.2)	29.9 (4.2)
Duration of T2DM, yrs	7.3 (5.7)	7.4 (5.9)	7.2 (5.7)	9.1 (9.9)	7.7 (6.5)	8.6 (6.8)	7.8 (5.2)	8.7 (6.8)	8.7 (5.0)	6.4 (5.1)	8.4 (6.2)	8.4 (5.7)
HbA1c, %	8.1 (0.9)	8.1 (0.9)	8.2 (1.0)	8.2 (1.0)	8.1 (0.7)	8.1 (1.0)	8.2 (0.9)	8.1 (1.0)	8.1 (0.9)	8.3 (1.0)	8.1 (0.9)	8.4 (0.8)
eGFR, mL/min/1.73 m^2	87.7 (18.2)	87.5 (17.4)	87.7 (17.5)	99.1 (20.1)	91.0 (16.2)	96.9 (20.1)	91.9 (20.4)	89.2 (19.2)	90.9 (20.3)	97.0 (21.5)	92.2 (20.2)	90.1 (22.4)
SBP, mmHg	129.6 (13.8)	131.6 (13.0)	130.6 (12.9)	133.1 (22.7)	131.7 (13.0)	133.4 (14.1)	128.7 (13.4)	127.9 (11.3)	128.1 (13.0)	130.6 (16.6)	130.7 (15.5)	130.6 (12.9)
Broad pool: race/treatment (n)^a
	White			Black				Asian			Other
	Non-ERTU (1113)	ERTU 5 mg (1336)	ERTU 15 mg (1283)	Non-ERTU (75)	ERTU 5 mg (78)	ERTU 15 mg (88)		Non-ERTU (190)	ERTU 5 mg (218)	ERTU 15 mg (240)	Non-ERTU (72)	ERTU 5 mg (84)	ERTU 15 mg (82)
Age, yrs	58.4 (10.2)	58.6 (10.0)	58.5 (10.1)	56.7 (9.0)	56.2 (10.9)	55.6 (10.7)		55.9 (10.5)	55.9 (10.8)	56.1 (10.0)	54.3 (10.4)	54.5 (10.0)	55.2 (10.6)
Male, n (%)	637 (57.2)	710 (53.1)	659 (51.4)	23 (30.7)	26 (33.3)	31 (35.2)		98 (51.6)	113 (51.8)	121 (50.4)	29 (40.3)	36 (42.9)	33 (40.2)
Body weight, kg	91.6 (19.5)	91.5 (19.9)	89.8 (18.3)	98.2 (28.6)	91.7 (21.9)	96.2 (22.4)		70.8 (15.5)	73.2 (17.3)	72.1 (14.7)	80.7 (25.4)	81.6 (19.8)	77.8 (16.9)
BMI, kg/m^2	32.3 (5.9)	32.6 (6.0)	32.2 (5.6)	35.3 (8.0)	32.9 (6.3)	34.8 (7.3)		26.8 (4.7)	27.6 (5.2)	27.4 (4.3)	30.0 (6.7)	31.3 (5.5)	30.0 (5.8)
Duration of T2DM, yrs	7.8 (6.3)	7.8 (6.3)	7.9 (6.4)	8.9 (8.0)	9.2 (8.9)	9.1 (6.4)		7.4 (5.4)	8.1 (6.3)	7.8 (5.6)	8.0 (6.9)	8.6 (7.3)	8.7 (6.5)
HbA1c, %^b	8.1 (0.9)	8.2 (0.9)	8.2 (0.9)	8.2 (1.1)	8.3 (0.8)	8.2 (1.0)		8.1 (0.9)	8.1 (1.0)	8.3 (0.9)	8.3 (1.0)	8.3 (0.9)	8.4 (1.0)
eGFR, mL/min/1.73 m^2^c	83.1 (22.6)	84.6 (21.6)	84.8 (22.1)	91.5 (21.4)	88.1 (22.4)	88.7 (23.8)		89.2 (20.3)	89.0 (23.0)	87.1 (21.4)	90.9 (25.5)	90.2 (23.3)	90.8 (23.1)
SBP, mmHg^d	130.3 (13.0)	131.5 (12.8)	131.2 (12.9)	131.3 (17.2)	129.5 (15.8)	129.6 (13.2)		127.8 (12.4)	127.5 (11.4)	127.6 (11.5)	126.2 (14.0)	126.6 (14.8)	126.4 (12.8)
Region
North America (excluding Central America)	374 (33.6)	458 (34.3)	400 (31.2)	53 (70.7)	54 (69.2)	61 (69.3)		42 (22.1)	48 (22.0)	66 (27.5)	12 (16.7)	17 (20.2)	20 (24.4)
South America (including Central America)	88 (7.9)	117 (8.8)	122 (9.5)	0 (0)	0 (0)	1 (1.1)		0 (0)	0 (0)	0 (0)	39 (54.2)	48 (57.1)	45 (54.9)
Europe (including Russia)	590 (53.0)	702 (52.5)	694 (54.1)	0 (0)	1 (1.3)	0 (0)		4 (2.1)	1 (0.5)	0 (0)	0 (0)	0 (0)	0 (0)
South Africa	12 (1.1)	13 (1.0)	9 (0.7)	22 (29.3)	23 (29.5)	25 (28.4)		8 (4.2)	11 (5.0)	7 (2.9)	18 (25.0)	18 (21.4)	16 (19.5)
Asia	41 (3.7)	38 (2.8)	55 (4.3)	0 (0)	0 (0)	0 (0)		135 (71.1)	154 (70.6)	165 (68.8)	0 (0)	0 (0)	0 (0)
Australia/New Zealand	8 (0.7)	8 (0.6)	3 (0.2)	0 (0)	0 (0)	1 (1.1)		1 (0.5)	4 (1.8)	2 (0.8)	3 (4.2)	1 (1.2)	1 (1.2)

Data are mean (standard deviation) unless otherwise stated.

^aTreatment groups in the broad pool comprise non-ertugliflozin (placebo, glimepiride or sitagliptin), ertugliflozin 5 mg (including ± sitagliptin 100 mg) and ertugliflozin 15 mg (including ± sitagliptin 100 mg).

^bN = 1108, 1320 and 1273 for non-ERTU, ERTU 5 mg and ERTU 15 mg in the White subgroup; N = 72 and 77 for non-ERTU and ERTU 5 mg in the Black subgroup; N = 187, 214 and 236 for non-ERTU, ERTU 5 mg and ERTU 15 mg in the Asian subgroup.

^cN = 1112 and 1335 for non-ERTU and ERTU 5 mg in the White subgroup.

^dN = 1109, 1335 and 1283 for non-ERTU, ERTU 5 mg and ERTU 15 mg in the White subgroup; N = 74 and 87 for non-ERTU and ERTU 15 mg in the Black subgroup.

Abbreviations. BMI, Body mass index; eGFR, Estimated glomerular filtration rate; ERTU, Ertugliflozin; HbA1c, Glycated hemoglobin; PBO, Placebo; SBP, Systolic blood pressure; T2DM, Type 2 diabetes mellitus.

Figure 1. Least squares mean change from baseline at Week 26 in (A) HbA1c, (B) body weight and (C) SBP by racial subgroup (placebo pool).

^aPlacebo-adjusted difference in LS means (95% CI).

Abbreviations. HbA1c, Glycated hemoglobin; LS, Least squares; SBP, Systolic blood pressure.

Table 3. Summary of AEs and pre-specified AEs.

							Race/Treatment, n^a (%)
	White			Black			Asian			Other
	Non-ERTU (1113)	ERTU 5 mg (1336)	ERTU 15 mg (1283)	Non-ERTU (75)	ERTU 5 mg (78)	ERTU 15 mg (88)	Non-ERTU (190)	ERTU 5 mg (218)	ERTU 15 mg (240)	Non-ERTU (72)	ERTU 5 mg (84)	ERTU 15 mg (82)
With ≥1 AE	712 (64.0)	836 (62.6)	782 (61.0)	47 (62.7)	50 (64.1)	55 (62.5)	125 (65.8)	127 (58.3)	146 (60.8)	56 (77.8)	61 (72.6)	66 (80.5)
With SAEs	57 (5.1)	84 (6.3)	75 (5.8)	4 (5.3)	4 (5.1)	5 (5.7)	13 (6.8)	18 (8.3)	14 (5.8)	6 (8.3)	4 (4.8)	4 (4.9)
Who discontinued treatment due to an AE	47 (4.2)	60 (4.5)	63 (4.9)	1 (1.3)	2 (2.6)	1 (1.1)	9 (4.7)	8 (3.7)	10 (4.2)	3 (4.2)	0 (0.0)	0 (0.0)
Who died	3 (0.3)	7 (0.5)	7 (0.5)	0 (0.0)	1 (1.3)	0 (0.0)	0 (0.0)	1 (0.5)	0 (0.0)	0 (0.0)	1 (1.2)	1 (1.2)
Pre-specified AEs of interest
UTI	87 (7.8)	96 (7.2)	93 (7.2)	7 (9.3)	5 (6.4)	6 (6.8)	14 (7.4)	10 (4.6)	10 (4.2)	7 (9.7)	7 (8.3)	10 (12.2)
GMI (Female)^b	19 (4.0)	58 (9.3)	72 (11.5)	1 (1.9)	3 (5.8)	7 (12.3)	0 (0.0)	3 (2.9)	6 (5.0)	0 (0.0)	7 (14.6)	3 (6.1)
GMI (Male)^c	2 (0.3)	34 (4.8)	28 (4.2)	0 (0.0)	1 (3.8)	0 (0.0)	0 (0.0)	4 (3.5)	2 (1.7)	0 (0.0)	2 (5.6)	3 (9.1)
Volume depletion AEs	14 (1.3)	26 (1.9)	14 (1.1)	2 (2.7)	1 (1.3)	2 (2.3)	1 (0.5)	4 (1.8)	3 (1.3)	0 (0.0)	1 (1.2)	4 (4.9)
	PBO (378)	ERTU 5 mg (382)	ERTU 15 mg (374)	PBO (31)	ERTU 5 mg (34)	ERTU 15 mg (37)	PBO (79)	ERTU 5 mg (77)	ERTU 15 mg (77)	PBO (27)	ERTU 5 mg (26)	ERTU 15 mg (22)
Symptomatic hypoglycemia (placebo pool)^d	9 (2.4)	11 (2.9)	8 (2.1)	0 (0.0)	0 (0.0)	0 (0.0)	1 (1.3)	4 (5.2)	3 (3.9)	0 (0.0)	0 (0.0)	1 (4.5)

^aTreatment groups in the broad pool comprise non-ertugliflozin (placebo, glimepiride or sitagliptin), ertugliflozin 5 mg (including ± sitagliptin 100 mg) and ertugliflozin 15 mg (including ± sitagliptin 100 mg).

^bOverall percentage calculated for the respective number of female patients in each treatment group. N = 476, 626 and 624 for non-ERTU, ERTU 5 mg and ERTU 15 mg in the White subgroup; N = 52, 52 and 57 for non-ERTU, ERTU 5 mg and ERTU 15 mg in the Black subgroup; N = 92, 105 and 119 for non-ERTU, ERTU 5 mg and ERTU 15 mg in the Asian subgroup; N = 43, 48 and 49 for non-ERTU, ERTU 5 mg and ERTU 15 mg in the Other subgroup.

^cOverall percentage calculated for the respective number of male patients in each treatment group. N = 637, 710 and 659 for non-ERTU, ERTU 5 mg and ERTU 15 mg in the White subgroup; N = 23, 26 and 31 for non-ERTU, ERTU 5 mg and ERTU 15 mg in the Black subgroup; N = 98, 113 and 121 for non-ERTU, ERTU 5 mg and ERTU 15 mg in the Asian subgroup; N = 29, 36 and 33 for non-ERTU, ERTU 5 mg and ERTU 15 mg in the Other subgroup.

^dPlacebo pool population, excluding rescue approach.

Abbreviations. AE, Adverse event; ERTU, Ertugliflozin; GMI, Genital mycotic infection; PBO, Placebo; SAE, Serious adverse event; UTI, Urinary tract infection.

Terra SG, Focht K, Davies M, et al. Phase III, efficacy and safety study of ertugliflozin monotherapy in people with type 2 diabetes mellitus inadequately controlled with diet and exercise alone. Diabetes Obes Metab. 2017;19(5):721–728.

 PubMed Web of Science ®Google Scholar

Rosenstock J, Frias J, Pall D, et al. Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy (VERTIS MET). Diabetes Obes Metab. 2018;20(3):520–529.

 PubMed Web of Science ®Google Scholar

Dagogo-Jack S, Liu J, Eldor R, et al. Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: the VERTIS SITA2 placebo-controlled randomized study. Diabetes Obes Metab. 2018;20(3):530–540.

 PubMed Web of Science ®Google Scholar

Hollander P, Liu J, Hill J, et al. Ertugliflozin compared with glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin: the VERTIS SU randomized study. Diabetes Ther. 2018;9(1):193–207.

 PubMed Web of Science ®Google Scholar

Miller S, Krumins T, Zhou H, et al. Ertugliflozin and sitagliptin co-initiation in patients with type 2 diabetes: The VERTIS SITA randomized study. Diabetes Ther. 2018;9(1):253–268.

 PubMed Web of Science ®Google Scholar

Pratley RE, Eldor R, Raji A, et al. Ertugliflozin plus sitagliptin versus either individual agent over 52 weeks in patients with type 2 diabetes mellitus inadequately controlled with metformin: the VERTIS FACTORIAL randomized trial. Diabetes Obes Metab. 2018;20(5):1111–1120.

 PubMed Web of Science ®Google Scholar

Grunberger G, Camp S, Johnson J, et al. Ertugliflozin in patients with stage 3 chronic kidney disease and type 2 diabetes mellitus: the VERTIS RENAL randomized study. Diabetes Ther. 2018;9(1):49–66.

 PubMed Web of Science ®Google Scholar

Liu J, Patel S, Cater NB, et al. Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2020;22(4):574–582.

 Google Scholar

Data availability statement

Upon request, and subject to certain criteria, conditions and exceptions (see https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information) Pfizer will provide access to individual de-identified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines and medical devices (1) for indications that have been approved in the US and/or EU or (2) in programs that have been terminated (i.e. development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary and statistical analysis plan. Data may be requested from Pfizer trials 24 months after study completion. The de-identified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer.