Long-term safety and tolerability of saxagliptin add-on therapy in older patients (aged ≥65 years) with type 2 diabetes

Figures & data

Table 1 Demographic and clinical characteristics of the pooled population

Characteristica	Age ≥65 years		Age <65 years
	SAXA 5 mg (n=99)	Placebo (n=106)	SAXA 5 mg (n=531)	Placebo (n=524)
Age, years	68.9 (3.3)	69.0 (3.2)	51.6 (8.4)	51.8 (8.8)
Women, n (%)	51 (52)	52 (49)	277 (52)	274 (52)
Race, n (%)
White	63 (64)	70 (66)	346 (65)	333 (64)
Asian	13 (13)	14 (13)	102 (19)	104 (20)
Black	4 (4)	3 (3)	24 (5)	18 (3)
Other	19 (19)	19 (18)	59 (11)	69 (13)
BMI, kg/m^2	29.1 (4.5)	29.2 (4.7)	30.1 (4.9)	30.2 (5.3)
Duration of T2DM, years	8.9 (7.1)	8.6 (7.2)	5.7 (4.9)	5.8 (5.1)
Creatinine clearance, mL/min, n (%)
≤80	56 (57)	57 (54)	81 (15)	79 (15)
>80	43 (43)	49 (46)	450 (85)	445 (85)
HbA1c, %	8.3 (0.9)	8.0 (0.8)	8.3 (1.0)	8.3 (1.0)
120-min PPG, mg/dL	318.0 (73.6)	306.8 (77.8)	302.5 (77.6)	304.7 (80.0)
FPG, mg/dL	166.0 (38.7)	163.0 (41.8)	173.1 (47.5)	172.5 (44.5)

Note:

a Mean (SD) unless specified as n (%).

Abbreviations: BMI, body mass index; FPG, fasting plasma glucose; HbA_1c, glycated hemoglobin; PPG, postprandial glucose; SAXA, saxagliptin; SD, standard deviation; T2DM, type 2 diabetes mellitus.

Table 2 AEs by category with saxagliptin versus placebo

Adverse event	Age ≥65 years		Age <65 years
	SAXA 5 mg (n=99)	Placebo (n=106)	SAXA 5 mg (n=531)	Placebo (n=524)
Any AE
Patients with event, n	84	93	447	431
Total exposure, person-years	32	25	199	172
IR per 100 person-years ± SE	260.6±29.3	388.8±40.9	227.6±10.8	250.9±12.1
Serious AE
Patients with event, n	8	14	49	44
Total exposure, person-years	147	134	750	667
IR per 100 person-years ± SE	5.7±2.0	9.9±2.7	6.5±0.9	6.6±1.0
Treatment-related AE
Patients with event, n	36	32	150	150
Total exposure, person-years	109	114	637	536
IR per 100 person-years ± SE	34.1±5.8	27.1±4.9	24.0±2.0	27.8±2.3
Treatment-related serious AE
Patients with event, n	1	0	4	3
Total exposure, person-years	152	146	799	689
IR per 100 person-years ± SE	0.5±0.5	–	0.5±0.3	0.4±0.3
AE leading to discontinuation
Patients with event, n	13	6	37	24
Total exposure, person-years	152	146	797	689
IR per 100 person-years ± SE	9.3±2.6	4.4±1.8	4.7±0.8	3.4±0.7
Serious AE leading to discontinuation
Patients with event, n	5	1	7	6
Total exposure, person-years	152	146	800	690
IR per 100 person-years ± SE	3.5±1.6	0.6±0.6	0.9±0.3	0.8±0.3
Death
Patients with event, n	1	0	1	6
Total exposure, person-years	152	146	801	690
IR per 100 person-years ± SE	0.8±0.8	–	0.1±0.1	0.9±0.4

Abbreviations: AE, adverse event; IR, incidence rate; SAXA, saxagliptin; SE, standard error.

Figure 1 IRRs of AEs by (A) category and (B) type with saxagliptin 5 mg versus placebo.

Notes: Error bars are 95% CIs. ^aPoint estimate could not be computed, and CI for IRR was not provided. In the elderly patients in the saxagliptin 5 mg and placebo groups, treatment-related serious AEs were reported in 1 and 0 patients and death occurred in 1 and 0 patients, respectively.
Abbreviations: AE, adverse event; CI, confidence interval; D/C, discontinuation; IRR, incidence rate ratio.

Table 3 AEs with an IR ≥5 events per 100 person-years in any groupa

IRb	Age ≥65 years		Age <65 years
	SAXA 5 mg (n=99)	Placebo (n=106)	SAXA 5 mg (n=531)	Placebo (n=524)
Nasopharyngitis	13.1	12.3	7.1	8.4
Influenza	8.7	11.5	5.9	7.0
Arthralgia	8.2	5.9	5.3	5.6
Hypertension	8.1	5.0	4.9	5.0
Back pain	7.9	6.1	4.4	5.6
Diarrhea	6.7	9.2	4.7	8.2
Upper respiratory tract infection	6.3	6.5	7.9	8.2
Urinary tract infection	5.5	9.2	9.7	8.1
Bronchitis	4.1	7.6	4.1	3.0
Peripheral edema	4.1	7.3	5.5	4.8
Headache	3.5	6.9	7.2	7.5
Extremity pain	3.4	5.3	3.4	4.7
Dizziness	2.8	6.7	1.9	3.9
Cough	2.7	9.1	3.3	4.4

Notes:

a Excluding hypoglycemia.

b Events are sorted in order of descending IR in the saxagliptin 5 mg group for patients ≥65 years.

Abbreviations: AE, adverse event; IR, incidence rate; SAXA, saxagliptin.

Table 4 AEs of special interest with saxagliptin 5 mg versus placebo

Adverse event	Age ≥65 years		Age <65 years
	SAXA 5 mg (n=99)	Placebo (n=106)	SAXA 5 mg (n=531)	Placebo (n=524)
Cardiovascular
Patients with event, n	3	2	6	11
Total exposure, person-years	148	144	794	688
IR per 100 person-years ± SE	2.1±1.3	1.5±1.1	0.8±0.3	1.6±0.5
Infectiona
Patients with event, n	54	62	283	269
Total exposure, person-years	87	66	425	382
IR per 100 person-years ± SE	67.7±9.9	102.4±13.5	67.1±4.0	70.2±4.3
Lymphopenia
Patients with event, n	5	3	6	5
Total exposure, person-years	148	144	796	687
IR per 100 person-years ± SE	3.2±1.5	2.2±1.3	0.8±0.3	0.7±0.3
Hypersensitivity
Patients with event, n	2	2	13	2
Total exposure, person-years	150	145	790	688
IR per 100 person-years ± SE	1.4±1.0	1.3±0.9	1.7±0.5	0.3±0.2
Skin-related
Patients with event, n	15	15	61	50
Total exposure, person-years	140	126	737	640
IR per 100 person-years ± SE	11.2±3.0	12.8±3.4	8.3±1.1	7.8±1.1
Hypoglycemia
Confirmedb
Patients with event, n	1	2	9	9
Total exposure, person-years	152	145	791	686
IR per 100 person-years ± SE	0.8±0.8	1.2±0.8	1.2±0.4	1.3±0.4
All reported
Patients with event, n	16	18	71	68
Total exposure, person-years	138	130	724	623
IR per 100 person-years ± SE	12.6±3.2	12.3±2.9	10.2±1.2	10.7±1.3

Notes:

a Based on system-organ class categorization of infections and infestations.

b Defined as episodes confirmed by fingerstick glucose ≤50 mg/dL and associated symptoms.

Abbreviations: IR, incidence rate; SAXA, saxagliptin; SE, standard error.