Table 1.
Apr2013-Dec2014 | Jan2015-Jun2016 | Jul2016-Dec2017 | Jan2018-Dec2019 | Linear trend (P) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SGLT-2i (n=1,875) | Metformin (n=271,143) | SD | SGLT2-i (n=2,765) | Metformin (n=228,142) | SD | SGLT2-i (n=2,390) | Metformin (n=173,647) | SD | SGLT2-i (n=2,083) | Metformin (n=137,416) | SD | ||
Baseline characteristics | |||||||||||||
Demographics | |||||||||||||
Age (mean, std.dev) | 57.53 (9.04) | 64.14 (9.58) | −0.24 | 59.77 (8.92) | 64.21 (9.52) | −0.20 | 60.58 (9.29) | 62.64 (10.11) | −0.15 | 62.13 (10.57) | 62.24 (10.73) | −0.01 | 0.040 |
Gender (Male) | 49.17 | 48.75 | 0.02 | 51.97 | 49.51 | 0.06 | 50.84 | 50.95 | 0.00 | 56.60 | 52.75 | 0.08 | 0.592 |
Region* | |||||||||||||
Northeast | 18.24 | 16.65 | 0.07 | 19.39 | 17.66 | 0.05 | 16.82 | 16.19 | 0.02 | 16.56 | 14.75 | 0.05 | 0.387 |
South | 52.37 | 41.98 | 0.14 | 53.16 | 43.96 | 0.14 | 53.97 | 46.40 | 0.13 | 49.35 | 45.58 | 0.07 | 0.204 |
Midwest | 17.28 | 23.21 | −0.13 | 14.79 | 21.11 | −0.17 | 15.73 | 20.70 | −0.14 | 18.10 | 21.34 | −0.08 | 0.342 |
West | 12.11 | 18.16 | −0.12 | 12.66 | 17.28 | −0.09 | 13.47 | 16.71 | −0.08 | 15.99 | 18.34 | −0.07 | 0.067 |
Medicare Advantage | 9.96 | 25.41 | −0.40 | 13.74 | 26.32 | −0.26 | 19.58 | 27.10 | −0.17 | 35.42 | 36.13 | −0.02 | 0.005 |
Race (White) | 79.22 | 77.36 | 0.08 | 76.18 | 75.70 | 0.04 | 72.09 | 72.07 | 0.02 | 63.57 | 63.71 | 0.00 | 0.020 |
Life-style risk factors | |||||||||||||
Obesity or Overweight | 27.95 | 23.22 | 0.12 | 35.37 | 31.33 | 0.10 | 43.14 | 40.41 | 0.05 | 48.73 | 48.36 | 0.01 | 0.006 |
Smoking | 8.05 | 12.55 | −0.06 | 12.30 | 15.25 | −0.04 | 15.86 | 17.55 | −0.03 | 20.16 | 20.05 | 0.00 | 0.040 |
Comorbidities | |||||||||||||
Diabetic Nephropathy | 2.40 | 1.74 | 0.09 | 3.47 | 2.69 | 0.07 | 5.65 | 4.12 | 0.08 | 9.07 | 5.31 | 0.14 | 0.315 |
Diabetic Neuropathy | 7.36 | 4.23 | 0.22 | 7.85 | 5.13 | 0.14 | 8.62 | 5.90 | 0.12 | 11.09 | 6.24 | 0.17 | 0.499 |
Diabetic Retinopathy | 2.03 | 1.11 | 0.10 | 2.03 | 1.09 | 0.09 | 1.17 | 1.02 | 0.02 | 3.65 | 1.43 | 0.14 | 0.892 |
CVD** | 21.65 | 28.23 | 0.04 | 25.61 | 28.16 | 0.04 | 28.66 | 26.43 | 0.09 | 37.01 | 26.01 | 0.25 | 0.114 |
Hyperlipidemia | 73.01 | 73.20 | 0.12 | 73.74 | 72.62 | 0.09 | 68.87 | 66.57 | 0.08 | 73.50 | 70.15 | 0.07 | 0.055 |
Hypertension | 68.05 | 71.45 | 0.08 | 73.82 | 73.22 | 0.10 | 73.47 | 71.68 | 0.07 | 76.62 | 70.97 | 0.13 | 0.431 |
CKD | 3.79 | 4.95 | 0.03 | 6.55 | 6.05 | 0.07 | 7.82 | 6.53 | 0.06 | 11.67 | 7.46 | 0.13 | 0.095 |
COPD | 6.93 | 10.24 | −0.02 | 7.92 | 10.22 | −0.03 | 9.37 | 9.47 | 0.01 | 10.32 | 9.82 | 0.01 | 0.212 |
History of Malignant Neoplasm | 7.04 | 10.14 | −0.02 | 8.93 | 10.23 | 0.01 | 8.45 | 9.43 | −0.02 | 9.79 | 8.96 | 0.03 | 0.367 |
Physician specialties † | |||||||||||||
Cardiologists | 2.77 | 5.33 | −0.07 | 3.25 | 5.21 | −0.07 | 4.18 | 5.00 | −0.03 | 7.06 | 5.20 | 0.08 | 0.111 |
Endocrinologists | 4.16 | 2.24 | 0.09 | 3.47 | 2.41 | 0.07 | 3.39 | 2.43 | 0.06 | 4.08 | 2.25 | 0.11 | 0.690 |
Internists | 46.83 | 64.05 | −0.37 | 45.35 | 65.65 | −0.42 | 44.52 | 66.68 | −0.45 | 45.13 | 67.02 | −0.45 | 0.073 |
Nurse practitioners or physician assistants | 2.24 | 4.75 | −0.08 | 2.82 | 5.81 | −0.13 | 4.48 | 6.24 | −0.07 | 4.46 | 7.21 | −0.12 | 0.744 |
Healthcare utilization | |||||||||||||
Any recent hospitalization†† | 1.12 | 4.07 | −0.17 | 1.23 | 3.81 | −0.15 | 1.21 | 3.55 | −0.15 | 2.69 | 3.88 | −0.07 | 0.125 |
Avg. length of hospitalizations (mean, std.dev) | 0.25 (1.43) | 0.49 (2.04) | −0.04 | 0.33 (1.66) | 0.47 (1.93) | −0.03 | 0.33 (1.37) | 0.44 (2.12) | −0.04 | 0.40 (1.50) | 0.47 (2.12) | −0.05 | 0.294 |
Number of ED visits (mean, Std.dev) | 0.54 (1.40) | 0.57 (1.47) | −0.02 | 0.56 (1.43) | 0.58 (1.51) | −0.03 | 0.60 (1.66) | 0.64 (1.68) | −0.04 | 0.71 (1.84) | 0.72 (1.91) | −0.02 | 0.940 |
Number of office visits (mean, std.dev) | 11.22 (9.78) | 9.76 (9.14) | 0.15 | 11.15 (9.81) | 9.65 (8.91) | 0.16 | 11.32 (10.23) | 9.84 (9.31) | 0.16 | 11.51 (9.89) | 9.86 (9.43) | 0.18 | 0.192 |
Number of HbA1c test orders (mean, std.dev) | 1.70 (1.17) | 1.53 (1.08) | 0.26 | 1.79 (1.15) | 1.60 (1.08) | 0.25 | 1.83 (1.17) | 1.63 (1.04) | 0.20 | 1.90 (1.19) | 1.66 (1.04) | 0.22 | 0.233 |
Brand/Generic ratio# (mean, std.dev) | −1.30 (1.20) | −1.61 (1.20) | 0.26 | −1.50 (1.19) | −1.79 (1.17) | 0.23 | −1.70 (1.21) | −1.92 (1.15) | 0.17 | −1.80 (1.19) | −2.01 (1.12) | 0.19 | 0.129 |
Number of unique medications (mean, std.dev) | 10.47 (8.08) | 10.41 (7.44) | 0.09 | 10.38 (7.93) | 10.36 (7.53) | 0.05 | 10.47 (8.15) | 10.16 (7.49) | 0.06 | 11.18 (8.87) | 10.31 (7.76) | 0.10 | 0.740 |
Copay for pharmacy cost ($, mean, std.dev) | 324.78 (429.14) | 354.29 (519.61) | 0.05 | 349.12 (516.60) | 336.45 (570.69) | 0.10 | 341.02 (624.02) | 302.06 (546.96) | 0.09 | 356.13 (588.57) | 292.89 (545.08) | 0.10 | 0.218 |
Preventive healthcare service## | 70.93 | 75.22 | −0.01 | 72.77 | 75.90 | 0.00 | 73.10 | 75.21 | −0.03 | 75.37 | 75.52 | 0.00 | 0.983 |
Concomitant medications | |||||||||||||
ACE inhibitors or ARBs | 59.05 | 63.18 | −0.14 | 60.26 | 63.81 | −0.10 | 62.18 | 65.09 | −0.09 | 60.20 | 65.12 | −0.09 | 0.156 |
Antithrombotic medications | 26.46 | 21.71 | 0.04 | 23.84 | 21.53 | 0.00 | 27.06 | 23.45 | 0.03 | 31.49 | 24.10 | 0.19 | 0.251 |
Beta blockers | 44.29 | 45.51 | −0.09 | 43.89 | 44.99 | −0.05 | 45.44 | 46.53 | −0.04 | 48.91 | 45.98 | 0.06 | 0.073 |
Calcium channel blockers | 29.53 | 31.85 | −0.09 | 30.84 | 31.47 | −0.04 | 30.49 | 32.04 | −0.04 | 28.32 | 32.16 | −0.03 | 0.111 |
Loop diuretics | 14.48 | 14.65 | 0.00 | 18.27 | 14.38 | 0.04 | 14.50 | 15.72 | 0.02 | 19.01 | 15.90 | 0.10 | 0.137 |
Statin | 58.77 | 66.49 | −0.19 | 60.02 | 67.41 | −0.15 | 65.77 | 70.12 | −0.11 | 64.55 | 71.08 | −0.09 | 0.005 |
Thiazides | 10.61 | 15.04 | −0.08 | 11.39 | 14.79 | −0.09 | 11.59 | 14.50 | −0.08 | 11.52 | 14.55 | −0.09 | 0.544 |
Laboratory values | |||||||||||||
HbA1c§ (%; mean, std.dev) | 7.82 (2.02) | 7.37 (1.55) | 0.27 | 7.58 (1.54) | 7.32 (1.55) | 0.18 | 7.50 (1.71) | 7.33 (1.55) | 0.10 | 7.83 (1.90) | 7.27 (1.53) | 0.30 | 0.951 |
Missing | 85.09 | 82.92 | −0.04 | 81.43 | 78.40 | −0.04 | 75.31 | 74.99 | −0.01 | 67.49 | 68.47 | −0.03 | 0.472 |
eGFR¶ (mL/min/1.73m2; mean, std.dev) | 100.81 (17.48) | 99.45 (16.11) | 0.09 | 99.88 (19.40) | 98.67 (16.26) | 0.06 | 101.27 (16.91) | 98.50 (16.59) | 0.17 | 95.79 (19.56) | 97.46 (16.86) | −0.09 | 0.493 |
Missing | 84.04 | 81.49 | −0.05 | 79.76 | 76.78 | −0.05 | 73.85 | 73.33 | 0.00 | 65.27 | 67.19 | −0.05 | 0.769 |
LDL (mg/dl; mean, std.dev) | 97.98 (47.35) | 98.71 (44.11) | −0.01 | 101.67 (38.09) | 101.92 (40.92) | −0.04 | 99.23 (39.40) | 102.92 (40.78) | −0.09 | 88.03 (43.43) | 100.66 (40.35) | −0.30 | 0.082 |
Missing | 84.89 | 82.43 | −0.03 | 82.26 | 78.64 | −0.02 | 76.23 | 75.81 | 0.00 | 69.71 | 70.75 | −0.03 | 0.896 |
HDL (mg/dl; mean, std.dev) | 45.88 (16.27) | 45.83 (77.02) | 0.00 | 45.96 (11.95) | 46.47 (14.28) | −0.04 | 46.06 (13.92) | 46.93 (49.73) | −0.02 | 45.70 (13.74) | 46.11 (13.17) | −0.03 | 0.454 |
Missing | 84.96 | 82.76 | −0.04 | 82.73 | 79.42 | −0.02 | 76.64 | 76.58 | −0.01 | 70.34 | 71.79 | −0.04 | 0.913 |
Total cholesterol (mg/dl; mean, std.dev) | 183.37 (57.21) | 180.97 (56.83) | 0.05 | 185.31 (43.10) | 188.28 (45.96) | −0.08 | 181.94 (46.87) | 188.46 (45.77) | −0.14 | 178.25 (43.17) | 184.19 (44.08) | −0.13 | 0.111 |
Missing | 84.70 | 82.73 | −0.05 | 82.52 | 79.12 | −0.02 | 76.23 | 76.12 | −0.01 | 69.90 | 71.11 | −0.03 | 0.584 |
Triglyceride (mg/dl; mean, std.dev) | 175.67 (117.28) | 176.65 (155.89) | 0.00 | 174.07 (177.49) | 183.80 (160.77) | −0.07 | 172.98 (126.02) | 184.07 (180.21) | −0.07 | 209.34 (199.19) | 181.93 (159.59) | 0.14 | 0.446 |
Missing | 84.83 | 82.79 | −0.04 | 82.57 | 79.43 | −0.03 | 76.23 | 76.37 | −0.01 | 69.96 | 71.29 | −0.04 | 0.643 |
SD: standardized difference; std.dev: standard deviation; HbA1c: hemoglobin A1c; CVD: cardiovascular disease; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; ED: emergency department.
Northeast (CT, MA, ME, NH, NJ, NY, PA, RI, VT)
South (AL, AR, DC, DE, FL, GA, KY, LA, MD, MS, NC, OK, SC, TN, TX, VA, WV)
Midwest (IA, IL, IN, KS, MI, MN, MO, ND, NE, OH, SD, WI)
West (AK, AZ, CA, CO, HI, ID, MT, NM, NV, OR, UT, WA, WY)
Defined as a history of myocardial infarction, stable or unstable angina, other ischemic heart diseases, transient ischemic attack, stroke, atherosclerotic peripheral vascular disease, or heart failure.
Defined as specialist visits occurred within 7 days prior to cohort entry.
Defined as hospitalization occurred within 30 days prior to cohort entry.
Added 1 to both numerator and denominator, then log-transformed.
Defined as administration of bone mineral density (BMD) test, colonoscopy, fecal occult blood test, mammography, pap smear, prostate-specific antigen (PSA) test, flu vaccine, or pneumococcal vaccine.
Measured 180 days prior to or on cohort entry.
Estimated using the quadratic GFR equation: . If serum creatinine <0.8 mg/dL, use 0.8 for serum creatinine.