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Table 4 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 with 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)

11,532

71.79

No antidiabetic drug

43,967

109.05

1.47 (1.32, 1.62)

1.27 (1.14, 1.40)

Sulfonylureas

40,852

67.48

0.92 (0.82, 1.01)

0.97 (0.87, 1.08)

Acarbose

9972

80.52

1.10 (0.97, 1.24)

1.01 (0.89, 1.14)

Meglitinides

6346

160.39

2.16 (1.91, 2.44)

1.54 (1.36, 1.73)

Insulin

3919

362.57

4.90 (0.68, 0.84)

3.30 (2.90, 3.75)

Metformin

67,237

56.33

0.76 (0.51, 0.83)

0.88 (0.78, 0.97)

Pioglitazone

1683

48.72

0.65 (0.51, 0.83)

0.74 (0.57, 0.95)

Rosiglitazone

186

75.00

0.91 (0.53, 1.54)

0.96 (0.56, 1.64)

Ischemic stroke

Antidiabetic drug (ref. = DPP4i)

11,532

37.02

No antidiabetic drug

43,967

61.47

1.61 (1.39, 1.85)

1.38 (1.19, 1.59)

Sulfonylureas

40,852

40.19

1.06 (0.91, 1.22)

1.07 (0.92, 1.23)

Acarbose

9972

41.51

1.10 (0.92, 1.29)

1.01 (0.85,1.18)

Meglitinides

6346

79.40

2.08 (1.75, 2.45)

1.48 (1.24, 1.74)

Insulin

3919

183.96

4.82 (4.10, 5.65)

3.37 (2.86, 3.96)

Metformin

67,237

36.78

0.97 (0.84, 1.10)

1.05 (0.91, 1.20)

Pioglitazone

1683

23.17

0.60 (0.43, 0.84)

0.67 (0.47, 0.94)

Rosiglitazone

186

42.85

1.01 (0.50, 2.02)

0.99 (0.49, 2.00)

Myocardial infarction

Antidiabetic drug (ref. = DPP4i)

11,532

8.67

No antidiabetic drug

43,967

11.05

1.38 (1.08, 1.76)

1.34 (1.04, 1.71)

Sulfonylureas

40,852

7.31

0.87 (0.68, 1.10)

0.99 (0.72, 1.26)

Acarbose

9972

7.82

0.92 (0.67, 1.26)

0.91 (0.66, 1.25)

Meglitinides

6346

13.86

1.65 (1.23, 2.20)

1.32 (0.98, 1.77)

Insulin

3919

27.81

3.25 (2.45, 4.30)

2.41 (1.80, 3.21)

Metformin

67,237

5.35

0.64 (0.50, 0.80)

0.78 (0.61, 0.98)

Pioglitazone

1683

7.12

0.83 (0.45, 1.52)

0.93 (0.50, 1.71)

Rosiglitazone

186

10.71

1.32 (0.33, 5.32)

1.46 (0.36, 5.81)

Heart failure

Antidiabetic drug (ref. = DPP4i)

11,532

30.26

No antidiabetic drug

43,967

48.71

1.52 (1.29, 1.78)

1.28 (1.08, 1.49)

Sulfonylureas

40,852

24.03

0.77 (0.65, 0.90)

0.86 (0.72, 1.02)

Acarbose

9972

36.19

1.17 (0.97, 1.39)

1.07 (0.89, 1.28)

Meglitinides

6346

77.36

2.45 (2.03, 2.95)

1.66 (1.38, 1.98)

Insulin

3919

178.60

5.72 (4.78, 6.83)

3.52 (2.88, 4.28)

Metformin

67,237

17.20

0.55 (0.46, 0.64)

0.68 (0.57, 0.80)

Pioglitazone

1683

23.17

0.73 (0.50, 1.07)

0.89 (0.59, 1.31)

Rosiglitazone

186

21.42

0.61 (0.22, 1.63)

0.72 (0.26, 1.97)

Hypoglycemia

Antidiabetic drug (ref. = DPP4i)

11,532

7.37

No antidiabetic drug

43,967

7.32

0.92 (0.70, 1.20)

0.83 (0.63, 1.07)

Sulfonylureas

40,852

10.13

1.31 (1.02, 1.67)

1.44 (1.12, 1.82)

Acarbose

9972

7.52

0.98 (0.72, 1.32)

0.92 (0.68, 1.24)

Meglitinides

6346

24.10

3.09 (2.35, 4.03)

2.20 (1.68, 2.88)

Insulin

3919

45.67

5.91 (4.50, 7.74)

3.73 (2.77, 5.01)

Metformin

67,237

3.56

0.46 (0.35, 0.59)

0.54 (0.42, 0.70)

Pioglitazone

1683

8.31

1.08 (0.61, 1.90)

1.25 (0.70, 2.20)

Rosiglitazone

186

21.42

2.31 (0.84, 6.32)

2.42 (0.88, 6.65)

  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)