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Table 5 Subgroup analysis of hazard ratios of cardiovascular diseases and hypoglycemic events associated with various antidiabetic drugs, as compared to DPP4i as reference, in the patients without CVD history

From: Risks of cardiovascular diseases associated with dipeptidyl peptidase-4 inhibitors and other antidiabetic drugs in patients with type 2 diabetes: a nation-wide longitudinal study

  Time at risk (person-years) Incidence rate (per 1000 person-years) Unadjusted HR (95 % CI) Adjusted HR* (95 % CI)
MACEs
Antidiabetic drug (ref. = DPP4i) 16,975 17.67
No antidiabetic drug 57,199 25.84 1.50 (1.29, 1.74) 1.38 (1.19, 1.60)
Sulfonylureas 69,766 17.55 0.99 (0.86, 1.15) 0.93 (0.80, 1.07)
Acarbose 12,828 23.38 1.33 (1.10, 1.60) 1.22 (1.01, 1.47)
Meglitinides 6756 48.10 2.73 (2.28, 3.26) 2.04(1.70, 2.44)
Insulin 5713 98.70 5.56 (4.70, 6.58) 5.48 (4.60, 6.50)
Metformin 105,576 14.65 0.83 (0.72, 0.96) 0.82 (0.70, 0.94)
Pioglitazone 2995 10.35 0.58 (0.39, 0.87) 0.61 (0.40, 0.90)
Rosiglitazone 318 12.56 0.68 (0.25, 1.83) 0.68 (0.25, 1.84)
Ischemic stroke
Antidiabetic drug (ref. = DPP4i) 16,975 9.60
No antidiabetic drug 57,199 16.11 1.70 (1.38, 2.07) 1.52 (1.23, 1.86)
Sulfonylureas 69,766 11.28 1.17 (0.96, 1.42) 1.04 (0.85, 1.27)
Acarbose 12,828 14.26 1.49 (1.15, 1.92) 1.34 (1.03, 1.74)
Meglitinides 6756 24.27 2.52 (1.96, 3.22) 1.85 (1.44, 2.36)
Insulin 5713 61.08 6.32 (5.02, 7.94) 6.56 (5.21, 8.27)
Metformin 105,576 10.32 1.07 (0.88, 1.29) 1.01 (0.82, 1.22)
Pioglitazone 2995 7.67 0.80 (0.49, 1.29) 0.81 (0.50, 1.32)
Rosiglitazone 318 12.56 1.21 (0.44, 3.27) 1.22 (0.44, 3.32)
Myocardial infarction
Antidiabetic drug (ref. = DPP4i) 16,975 2.82
No antidiabetic drug 57,199 3.91 1.55 (1.09, 2.20) 1.56 (1.09, 2.22)
Sulfonylureas 69,766 2.39 0.88 (0.63, 1.22) 0.93 (0.66, 1.29)
Acarbose 12,828 2.96 1.08 (0.68, 1.70) 1.09 (0.69, 1.71)
Meglitinides 6756 5.47 2.02 (1.33, 3.04) 1.78 (1.17, 2.69)
Insulin 5713 10.67 3.84 (2.54, 5.79) 3.38 (2.23, 5.10)
Metformin 105,576 1.99 0.74 (0.53, 1.02) 0.81 (0.58, 1.13)
Pioglitazone 2995 1.66 0.59 (0.23, 1.49) 0.63 (0.24, 1.60)
Rosiglitazone 318 0 0 0
Heart failure
Antidiabetic drug (ref. = DPP4i) 16,975 6.18
No antidiabetic drug 57,199 7.18 1.19 (0.92, 1.52) 1.13 (0.87, 1.45)
Sulfonylureas 69,766 4.61 0.75 (0.58, 0.95) 0.73 (0.57, 0.94)
Acarbose 12,828 7.09 1.15 (0.84, 1.56) 1.06 (0.78, 1.44)
Meglitinides 6756 20.86 3.38 (2.55, 4.46) 2.45 (1.85, 3.22)
Insulin 5713 33.95 5.45 (4.17, 7.10) 4.75(3.54, 6.35)
Metformin 105,576 2.97 0.48 (0.37, 0.61) 0.51 (0.39, 0.65)
Pioglitazone 2995 1.66 0.27 (0.10, 0.66) 0.29 (0.11, 0.71)
Rosiglitazone 318 0 0 0
Hypoglycemia
Antidiabetic drug (ref. = DPP4i) 16,975 4.77
No antidiabetic drug 57,199 3.63 0.69 (0.51, 0.92) 0.69 (0.51, 0.92)
Sulfonylureas 69,766 3.92 0.76 (0.59, 0.98) 0.78 (0.60, 1.00)
Acarbose 12,828 4.52 0.91 (0.65, 1.24) 0.89 (0.64, 1.22)
Meglitinides 6756 12.58 2.44 (1.70, 3.49) 1.93 (1.33, 2.77)
Insulin 5713 35.17 6.95 (5.17, 9.34) 5.47 (4.00, 7.48)
Metformin 105,576 2.13 0.41 (0.30, 0.55) 0.46 (0.34, 0.61)
Pioglitazone 2995 4.34 0.84 (0.47, 1.50) 0.93 (0.52, 1.65)
Rosiglitazone 318 6.28 0.89 (0.22, 3.57) 0.91 (0.23, 3.56)
  1. CVD cardiovascular disease, HR hazard ratio, CI confidence interval, MACEs major adverse cardiovascular events, DPP-4 inhibitors dipeptidyl peptidase-4 inhibitors
  2. * Adjusted hazard ratios were estimated from the Cox models adjusted for age, sex, diabetes duration, comorbidity history (hypertension, hyperlipidemia, coronary artery diseases, stroke, myocardial infarction, heart failure, Charlson comorbidity index), diabetic complications (via adapted diabetic complication severity index), co-medications (α-blockers, β-blockers, diuretics, calcium channel blockers, angiotensin-II-converting enzyme inhibitors/angiotensin receptor blockers, lipid-lowering agents, anti-platelet agents/anticoagulants, nitroglycerin, digoxin)