Antihyperglycemic drugs and cardiovascular outcomes in type 2 diabetes

Article Figures & Data

TABLE 1

Randomized controlled trials of antihyperglycemic agents in patients with type 2 diabetes or impaired glucose tolerance

Drug class	Agent (trial)
Sulfonylureas Various	(UKPDS)^2,4
Biguanides Metformin	(UKPDS)¹⁵
Meglitinides Nateglinide	(NAVIGATOR)²¹
Alpha-glucosidase inhibitors	Acarbose (STOP-NIDDM)^22,23
Thiazolidinediones	Pioglitazone (PROactive)²⁶ Rosiglitazone (RECORD)¹³ Rosiglitazone (BARI 2D)²⁸
Dopaminergic agents	Bromocriptine quick-release (Cycloset Safety Trial)²⁹
DPP-4 inhibitors	Alogliptin (EXAMINE)^30,34 Saxagliptin (SAVOR-TIMI 53)^31,33 Sitagliptin (TECOS)³²
GLP-1 receptor agonists	Lixisenatide (ELIXA)⁴⁰
SGLT-2 inhibitors	(EMPA-REG OUTCOME trial)⁴³
Insulin	(DIGAMI-1, DIGAMI-2)^44–46 (HI-5)⁴⁷ Prandial vs basal insulin (HEART2D)^48,49 Basal insulin (ORIGIN)⁵⁰

DPP-4 = dipeptidyl peptidase-4; GLP-1 = glucagon-like peptide-1; SGLT-2 = sodium-glucose cotransporter-2.

TABLE 2

DPP-4 inhibitors: Patient characteristics and outcomes in randomized controlled trials

Patient characteristics	Drug (trial)
Patient characteristics	Alogliptin (EXAMINE)^30,34	Saxagliptin (SAVOR- TIMI-53)^31,33	Sitagliptin (TECOS)³²
N	5,380	16,492	14,671
Age (mean or median)	61.0	65.1	65.4
Gender (male/female), %	68/32	67/33	71/29
BMI (mean or median)	28.7	31.1	30.2
DM duration (mean or median), yrs	7.2	10.3	11.6
Median study follow-up, yrs	1.5	2.1	3.0
HbA1c at baseline, mean % ± SD	8.0 ±1.1	8.0 ±1.4	7.2 ±0.5
Decrease in HbA1c during trial, mean	0.36%	0.20%	0.29%
Presentation at baseline	Acute coronary syndrome	CVD or multiple risk factors	CVD
Heart failure at baseline (%)	28	13	18
Outcomes
Primary CV end point; HR (95% CI)	0.96 (≤ 1.16)	1.00 (0.89–1.12)	0.98 (0.89–1.08)
Death from any cause; HR (95% CI)	0.88 (0.71–1.09)	1.11 (0.96–1.27)	1.01 (0.90–1.14)
Death from CV causes; HR (95% CI)	0.85 (0.66–1.10)	1.03 (0.87–1.22)	1.03 (0.89–1.19)
Hospitalization for heart failure; HR (95% CI)	1.07 (0.79–1.46)	1.27 (1.07–1.51)	0.98 (0.81–1.19)
Death from CV causes + hospitalization for heart failure; HR (95% CI)	1.00 (0.82–1.21)	Not reported	1.01 (0.88–1.16

BMI = body mass index; CI = confidence interval; CV = cardiovascular; CVD = cardiovascular disease; DPP-4 = dipeptidyl peptidase-4; DM = diabetes mellitus; HbA1c = hemoglobin A1c; HR = hazard ratio; SD = standard deviation.