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Table 3 Hazard ratios of cardiovascular diseases and hypoglycemic events associated with various antidiabetic drugs, as compared to DPP4i as reference

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)

p value

MACEs

Antidiabetic drug (ref. = DPP4i)

28,508

39.56

No antidiabetic drug

101,166

62.02

1.52 (1.39, 1.65)

1.31 (1.20, 1.43)

<0.0001

Sulfonylureas

110,618

35.99

0.89 (0.81, 0.96)

0.96 (0.88, 1.05)

0.3942

Acarbose

22,800

48.37

1.20 (1.08, 1.33)

1.07 (0.96, 1.18)

0.2098

Meglitinides

13,103

102.49

2.52 (2.27, 2.78)

1.68 (1.52, 1.86)

<0.0001

Insulin

9632

206.06

5.08 (4.60, 5.61)

3.73 (3.35, 4.14)

<0.0001

Metformin

172,813

30.87

0.76 (0.69, 0.82)

0.87 (0.79, 0.94)

0.0009

Pioglitazone

4678

24.15

0.59 (0.47, 0.73)

0.70 (0.56, 0.86)

0.0011

Rosiglitazone

504

35.64

0.78 (0.48, 1.23)

0.89 (0.55, 1.42)

0.6296

Ischemic stroke

Antidiabetic drug (ref. = DPP4i)

28,508

20.69

No antidiabetic drug

101,166

35.83

1.68 (1.49, 1.89)

1.42 (1.26, 1.60)

<0.0001

Sulfonylureas

110,618

21.95

1.03 (0.92, 1.16)

1.06 (0.94, 1.19)

0.3465

Acarbose

22,800

26.18

1.24 (1.08, 1.43)

1.09 (0.94, 1.25)

0.2432

Meglitinides

13,103

50.98

2.39 (2.07, 2.75)

1.58 (1.37, 1.81)

<0.0001

Insulin

9632

111.07

5.23 (4.58, 5.97)

3.99 (3.47, 4.56)

<0.0001

Metformin

172,813

20.61

0.97 (0.86, 1.08)

1.03 (0.92, 1.15)

0.5630

Pioglitazone

4678

13.25

0.62 (0.47, 0.82)

0.71 (0.53, 0.94)

0.0166

Rosiglitazone

504

23.76

0.99 (0.55, 1.75)

1.06 (0.59, 1.87)

0.8551

Myocardial infarction

Antidiabetic drug (ref. = DPP4i)

28,508

5.19

No antidiabetic drug

101,166

7.01

1.47 (1.20, 1.80)

1.45 (1.18, 1.78)

0.0003

Sulfonylureas

110,618

4.21

0.83 (0.68, 1.01)

0.98 (0.80, 1.78)

0.8257

Acarbose

22,800

5.08

1.00 (0.77, 1.29)

0.98 (0.75, 1.27)

0.8993

Meglitinides

13,103

9.53

1.89 (1.49, 2.39)

1.49 (1.17, 1.90)

0.0011

Insulin

9632

17.64

3.43 (2.72, 4.33)

2.77 (2.17, 3.51)

<0.0001

Metformin

172,813

3.30

0.66 (0.54, 0.79)

0.80 (0.50, 1.39)

0.0234

Pioglitazone

4678

3.63

0.70 (0.42, 1.16)

0.84 (0.50, 1.39)

0.5007

Rosiglitazone

504

3.96

0.81 (0.20, 3.23)

0.92 (0.23, 3.63)

0.9037

Heart failure

Antidiabetic drug (ref. = DPP4i)

28,508

15.92

No antidiabetic drug

101,166

25.23

1.50 (1.30, 1.71)

1.28 (1.11, 1.47)

0.0004

Sulfonylureas

110,618

11.78

0.71 (0.62, 0.81)

0.86 (0.74, 1.08)

0.0322

Acarbose

22,800

19.82

1.21 (1.03, 1.42)

1.08 (0.92, 1.26)

0.3227

Meglitinides

13,103

48.23

2.91 (2.48, 3.40)

1.85 (1.58, 2.16)

<0.0001

Insulin

9632

92.80

5.67 (4.87, 6.58)

3.71 (3.14, 4.37)

<0.0001

Metformin

172,813

8.51

0.51 (0.44, 0.59)

0.66 (0.57, 0.75)

<0.0001

Pioglitazone

4678

9.40

0.57 (0.39, 0.80)

0.76 (0.53, 1.07)

0.1229

Rosiglitazone

504

7.92

0.42 (0.15, 1.13)

0.53 (0.19, 1.46)

0.2226

Hypoglycemia

Antidiabetic drug (ref. = DPP4i)

28,508

5.82

No antidiabetic drug

101,166

5.23

0.83 (0.67, 1.00)

0.76 (0.62, 0.92)

0.0053

Sulfonylureas

110,618

6.21

1.00 (0.84, 1.19)

1.08 (0.91, 1.29)

0.3621

Acarbose

22,800

5.83

0.96 (0.77, 1.19)

0.90 (0.72, 1.11)

0.3402

Meglitinides

13,103

18.16

2.91 (2.35, 3.59)

2.09 (1.68, 2.58)

<0.0001

Insulin

9632

39.44

6.41 (5.24, 7.84)

4.55 (3.67, 5.64)

<0.0001

Metformin

172,813

2.69

0.43 (0.35, 0.52)

0.50 (0.41, 0.60)

<0.0001

Pioglitazone

4678

5.77

0.93 (0.62, 1.40)

1.07 (0.71, 1.60)

0.7471

Rosiglitazone

504

11.88

1.50 (0.66, 3.37)

1.58 (0.70, 3.55)

0.2679

  1. The results in italics above indicate significant findings in the Cox models
  2. HR hazard ratio, CI confidence interval, MACEs major adverse cardiovascular events, DPP4i dipeptidyl peptidase-4 inhibitors
  3. * 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)