Table 1:
Baseline characteristics of participants who were newly dispensed sodium–glucose cotransporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors in Ontario (2015–2017)
| Characteristic* | Observed data | Weighted data† | ||||
|---|---|---|---|---|---|---|
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| No. (%) of participants‡ | Standardized difference,§ % | No. (%) of participants‡ | Standardized difference,§ % | |||
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| Using SGLT2 inhibitors n = 19 611 | Using DPP4 inhibitors n = 19 483 | Using SGLT2 inhibitors n = 19 611 | Using DPP4 inhibitors n = 19 775 | |||
| Demographic | ||||||
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| Age, yr; mean ± SD | 71.4 ± 4.9 | 74.1 ± 6.3 | 47 | 71.4 ± 4.9 | 71.4 ± 5.0 | 1 |
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| Sex, female | 7903 (40.3) | 9325 (s47.9) | 15 | 7903 (40.3) | 8104 (41.0) | 1 |
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| Rural residence¶ | 2192 (11.2) | 2088 (10.7) | 2 | 2192 (11.2) | 2423 (12.3) | 3 |
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| Neighbourhood income quintile** | ||||||
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| 1 (lowest) | 4350 (22.2) | 4566 (23.4) | 3 | 4350 (22.2) | 4397 (22.2) | 0 |
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| 2 | 4236 (21.6) | 4390 (22.5) | 2 | 4236 (21.6) | 4328 (21.9) | 1 |
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| 3 | 4011 (20.5) | 3953 (20.3) | 0 | 4044 (20.6) | 4047 (20.5) | 0 |
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| 4 | 3679 (18.8) | 3513 (18.0) | 2 | 3679 (18.8) | 3683 (18.6) | 1 |
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| 5 (highest) | 3302 (16.8) | 3043 (15.6) | 3 | 3302 (16.8) | 3321 (16.8) | 0 |
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| Prescriber specialty | ||||||
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| Cardiology | 413 (2.1) | 108 (0.6) | 13 | 413 (2.1) | 506 (2.6) | 3 |
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| Endocrinology | 3786 (19.3) | 1475 (7.6) | 35 | 3786 (19.3) | 3574 (18.1) | 3 |
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| Family medicine | 12 798 (65.3) | 15 685 (80.5) | 35 | 12 798 (65.3) | 12 927 (65.4) | 0 |
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| Internal medicine | 1139 (5.8) | 540 (2.8) | 15 | 1139 (5.8) | 1232 (6.2) | 2 |
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| Nephrology | 217 (1.1) | 97 (0.5) | 7 | 217 (1.1) | 234 (1.2) | 1 |
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| Other | 167 (0.9) | 317 (1.6) | 6 | 167 (0.9) | 171 (0.9) | 0 |
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| Missing | 1091 (5.6) | 1261 (6.5) | 4 | 1091 (5.6) | 1131 (5.7) | 0 |
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| Comorbidity†† | ||||||
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| Duration of diabetes, yr; mean ± SD | 13.8 ± 6.9 | 12.0 ± 7.2 | 25 | 13.8 ± 6.9 | 13.8 ± 7.1 | 1 |
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| Diabetic retinopathy | 168 (0.9) | 140 (0.7) | 2 | 168 (0.9) | 172 (0.9) | 0 |
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| Diabetic neuropathy | 231 (1.2) | 257 (1.3) | 1 | 231 (1.2) | 223 (1.1) | 1 |
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| Hypoglycemia | 115 (0.6) | 185 (0.9) | 3 | 115 (0.6) | 127 (0.6) | 0 |
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| Hyperglycemic emergency | 82 (0.4) | 47 (0.2) | 4 | 75 (0.4) | 47 (0.2) | 4 |
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| Previous acute kidney injury | 351 (1.8) | 702 (3.6) | 11 | 351 (1.8) | 395 (2.0) | 1 |
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| Previous acute urinary retention | 252 (1.3) | 452 (2.3) | 8 | 252 (1.3) | 237 (1.2) | 1 |
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| Chronic lung disease | 3885 (19.8) | 3976 (20.4) | 1 | 3885 (19.8) | 4049 (20.5) | 2 |
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| Cancer (including skin) | 5586 (28.5) | 5987 (30.7) | 5 | 5586 (28.5) | 5579 (28.2) | 1 |
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| Stroke | 270 (1.4) | 556 (2.9) | 10 | 270 (1.4) | 256 (1.3) | 1 |
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| Atrial fibrillation | 717 (3.7) | 930 (4.8) | 5 | 717 (3.7) | 702 (3.5) | 1 |
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| Coronary artery bypass graft surgery | 513 (2.6) | 372 (1.9) | 5 | 513 (2.6) | 514 (2.6) | 0 |
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| Percutaneous coronary intervention | 1051 (5.4) | 777 (4.0) | 7 | 1051 (5.4) | 1010 (5.1) | 1 |
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| Pacemaker | 543 (2.8) | 561 (2.9) | 1 | 543 (2.8) | 518 (2.6) | 1 |
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| Congestive heart failure | 1649 (8.4) | 1876 (9.6) | 4 | 1649 (8.4) | 1674 (8.5) | 0 |
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| Chronic liver disease | 947 (4.8) | 978 (5.0) | 1 | 947 (4.8) | 916 (4.6) | 1 |
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| Peripheral vascular disease | 202 (1.0) | 218 (1.1) | 1 | 202 (1.0) | 188 (1.0) | 0 |
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| Hypertension | 15 302 (78.0) | 13 528 (69.4) | 20 | 15 302 (78.0) | 15 477 (78.3) | 1 |
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| Previous urinary tract infection | 578 (2.9) | 1015 (5.2) | 12 | 578 (2.9) | 661 (3.3) | 2 |
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| Charlson Comorbidity Index score‡‡ | ||||||
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| 0 | 16 722 (85.3) | 15 676 (80.5) | 13 | 16 722 (85.3) | 16 998 (86.0) | 2 |
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| 1 | 943 (4.8) | 1147 (5.9) | 5 | 943 (4.8) | 852 (4.3) | 2 |
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| 2 | 862 (4.4) | 1044 (5.4) | 5 | 862 (4.4) | 862 (4.4) | 0 |
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| 3 | 1084 (5.5) | 1616 (8.3) | 11 | 1084 (5.5) | 1063 (5.4) | 0 |
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| Medication§§ | ||||||
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| ACE inhibitor | 7155 (36.5) | 6128 (31.5) | 11 | 7155 (36.5) | 7271 (36.8) | 1 |
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| ARB | 4754 (24.2) | 4095 (21.0) | 8 | 4754 (24.2) | 4856 (24.6) | 1 |
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| ACE or ARB | 11 796 (60.1) | 10 124 (52.0) | 16 | 11 796 (60.1) | 12 008 (60.7) | 1 |
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| ASA¶¶ | 436 (2.2) | 395 (2.0) | 1 | 436 (2.2) | 497 (2.5) | 2 |
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| β-Blocker | 6427 (32.8) | 5679 (29.1) | 8 | 6427 (32.8) | 6442 (32.6) | 0 |
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| Calcium-channel blocker | 6167 (31.4) | 5540 (28.4) | 7 | 6167 (31.4) | 6205 (31.4) | 0 |
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| NSAID*** | 2076 (10.6) | 1684 (8.6) | 7 | 2076 (10.6) | 2144 (10.8) | 1 |
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| Statin | 14 887 (75.9) | 12 257 (62.9) | 28 | 14 887 (75.9) | 15 031 (76.0) | 0 |
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| Proton pump inhibitor | 4264 (21.7) | 4137 (21.2) | 1 | 4264 (21.7) | 4352 (22.0) | 1 |
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| Any diuretic | 4240 (21.6) | 4231 (21.7) | 0 | 4240 (21.6) | 4460 (22.6) | 2 |
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| Hypoglycemic medication§§ | ||||||
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| Insulin | 5229 (26.7) | 2508 (12.9) | 35 | 5229 (26.7) | 5582 (28.2) | 3 |
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| Acarbose | 366 (1.9) | 141 (0.7) | 11 | 366 (1.9) | 447 (2.3) | 3 |
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| Gliclazide | 6606 (33.7) | 4385 (22.5) | 25 | 6606 (33.7) | 6870 (34.7) | 2 |
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| Glyburide | 719 (3.7) | 1004 (5.2) | 7 | 719 (3.7) | 740 (3.7) | 0 |
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| Metformin | 15 765 (80.4) | 12 738 (65.4) | 34 | 15 765 (80.4) | 15 837 (80.1) | 1 |
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| Repaglinide | 6 (0.0) | 10 (0.1) | 4 | 6 (0.0) | 23 (0.1) | 4 |
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| Rosiglitazone maleate | 13 (0.1) | 16 (0.1) | 0 | 13 (0.1) | 12 (0.1) | 0 |
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| Pioglitazine | 100 (0.5) | 104 (0.5) | 0 | 100 (0.5) | 108 (0.5) | 0 |
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| Laboratory test result‡‡‡ | ||||||
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| Baseline eGFR,§§§ mL/min/1.73 m2; mean ± SD | 77 ± 14 | 73 ± 16 | 26 | 77 ± 14 | 77 ± 16 | 0 |
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| eGFR > 60 mL/min/1.73 m2 | 16 786 (86) | 14 405 (74) | 29 | 16 786 (86) | 16 009 (81) | 12 |
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| eGFR = 45–60 mL/min/1.73 m2 | 2825 (14.4) | 5078 (25.9) | 29 | 2825 (14.4) | 3766 (19.0) | 12 |
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| Baseline serum creatinine, μmol/L; mean ± SD | 79.6 ± 18.1 | 81.2 ± 20.2 | 8 | 79.6 ± 18.1 | 79.7 ± 20.3 | 0 |
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| Potassium data available | 5556 (28.3) | 7072 (36.3) | 17 | 5556 (28.3) | 6110 (30.9) | 6 |
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| Baseline potassium, mEq/L; mean ± SD | 4.5 ± 0.4 | 4.4 ± 0.5 | 13 | 4.5 ± 0.4 | 4.5 ± 0.4 | 7 |
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| Glycosylated hemoglobin available | 6516 (33.2) | 8071 (41.4) | 17 | 6516 (33.2) | 7288 (36.9) | 8 |
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| Glycosylated hemoglobin, %; mean ± SD | 7.8 ± 1.2 | 7.7 ± 1.3 | 12 | 7.8 ± 1.2 | 7.8 ± 1.2 | 2 |
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| Urine ACR available | 14 637 (74.6) | 12 381 (63.5) | 24 | 14 637 (74.6) | 14 240 (72.0) | 6 |
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| Baseline ACR category, mg/mmol | ||||||
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| Undetected | 9424 (48.1) | 7903 (40.6) | 15 | 9424 (48.1) | 9129 (46.2) | 4 |
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| 3–30 | 4263 (21.7) | 3729 (19.1) | 6 | 4263 (21.7) | 4288 (21.7) | 0 |
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| > 30 | 950 (4.8) | 749 (3.8) | 5 | 950 (4.8) | 823 (4.2) | 3 |
Note: ACE = angiotensin-converting-enzyme, ACR = albumin-to-creatinine ratio, ARB = angiotensin receptor blocker, ASA = acetylsalicylic acid, DPP4 = dipeptidyl peptidase-4, ED = emergency department, eGFR = estimated glomerular filtration rate, NSAID = nonsteroidal anti-inflammatory drug, SD = standard deviation, SGLT2 = sodium–glucose cotransporter-2.
Unless otherwise specified, we assessed baseline characteristics on the date that the patient filled their prescription (the cohort entry date).
Weighted using inverse probability of treatment weighting based on propensity scores, using weights to estimate the average treatment effect in the treated group. Patients in the reference group were weighted as [propensity score/(1 – propensity score)]. This method produces a weighted pseudosample of patients in the reference group with the same distribution of measured covariates as the exposure group.44–46 When we evaluated plots of the distribution of propensity scores before and after weighting, there was sufficient overlap between the 2 groups before weighting (summarized in Appendices 1R and 1S, available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.191283/-/DC1).
Binary variables are presented as number and percentage, and continuous variables as mean ± SD (exception: health care use, median [IQR]).
The difference between the groups divided by the pooled SD: a value greater than 10% is interpreted as a meaningful difference.43
Rural residence was defined as a population of < 10 000 people. Residential information was not available for 33 (0.2%) SGLT2 inhibitor users and 18 (0.1%) DPP4 inhibitor users in the unweighted cohort. We reclassified missing values in the unweighted cohort into the “Not rural” category during weighting.
Income was categorized into fifths of average neighbourhood income on the cohort entry date.
The prevalence of comorbidities was defined using a 5-year look-back period before the cohort entry date.
We calculated the Charlson Comorbidity Index score49,50 using 5 years of data for admissions to hospital. “No admissions to hospital” received a score of 0.
Use of medications and hypoglycemic agents was evaluated in the 120-day period before the cohort entry date (the Ontario Drug Benefit program dispenses a maximum 100-day supply).
Includes dispensed ASA use only; value does not account for over-the-counter ASA use.
Excludes ASA.
Total number of health care visits in the 12-month period before the cohort entry date.
Most recent laboratory test results in the 1- to 365-day period before the cohort entry date.
eGFR was calculated using the Chronic Kidney Disease (CKD)-Epidemiology (EPI) equation.51