Intensification of major second-line therapies in subcohort 2‡ (N = 278,188)
| . | GLP-1RA . | INS . | TZD . | DPP-4i . | SU . | All . |
|---|---|---|---|---|---|---|
| N | 11,431 | 36,337 | 28,841 | 46,822 | 149,109 | 278,188 |
| Follow-up from second ADD initiation, years* | 3.85 (2.24) | 3.56 (2.09) | 5.40 (2.66) | 3.37 (1.81) | 4.09 (2.35) | 4.02 (2.33) |
| Initiated third ADD, n (% of N) | 5,942 (52) | 10,677 (29) | 18,788 (65) | 23,840 (51) | 81,980 (55) | 144,106 |
| Initiated INS, n (% of N) | 3,285 (29) | 8,223 (29) | 9,633 (21) | 45,293 (30) | 67,812 | |
| Restricted mean time to a third ADD, years§ | 4.23 (4.14, 4.32) | 6.15 (6.09, 6.21) | 3.53 (3.49, 3.58) | 4.12 (4.07, 4.17) | 3.91 (3.88, 3.93) | 4.18 (4.17, 4.20) |
| Restricted mean time to INS, years§ | 6.58 (6.49, 6.67) | 6.82 (6.78, 6.87) | 7.14 (7.09, 7.18) | 6.26 (6.23, 6.28) | 6.51 (6.49, 6.53) | |
| Added third ADD | ||||||
| n1 (% of N) | 4,522 (40) | 9,675 (27) | 12,481 (43) | 18,881 (40) | 73,776 (49) | 121,559 (44) |
| HbA1c, %* | 8.2 (1.7) | 8.9 (2) | 8.1 (1.8) | 8.5 (1.8) | 8.6 (1.7) | 8.5 (1.8) |
| HbA1c, mmol/mol† | 66 | 74 | 65 | 69 | 70 | 69 |
| HbA1c ≥7.5% (58 mmol/mol), n (% of n1) | 1,798 (61) | 4,953 (74) | 4,102 (55) | 8,968 (69) | 32,611 (72) | 53,100 (69) |
| HbA1c ≥8% (64 mmol/mol), n (% of n1) | 1,364 (47) | 4,160 (62) | 3,101 (42) | 6,974 (54) | 26,231 (58) | 42,330 (55) |
| GLP-1RA as third ADD, n (% of n1) | 2,125 (22) | 1,532 (12) | 1,643 (9) | 5,662 (8) | 11,230 (9) | |
| INS as third ADD, n (% of n1) | 2,356 (52) | 3,338 (27) | 5,472 (29) | 20,483 (28) | 32,447 (27) | |
| TZD as third ADD, n (% of n1) | 241 (5) | 688 (7) | 1,425 (8) | 19,010 (26) | 21,472 (18) | |
| DPP-4i as third ADD, n (% of n1) | 481 (11) | 2,488 (26) | 3,804 (30) | 25,216 (34) | 32,696 (27) | |
| SU as third ADD, n (% of n1) | 865 (19) | 3,090 (32) | 3,048 (24) | 7,556 (40) | 14,844 (12) | |
| SGLT2i as third ADD, n (% of n1) | 521 (12) | 938 (10) | 138 (1) | 2,399 (13) | 2,077 (3) | 6,095 (5) |
| Switched to third ADD | ||||||
| n2 (% of N) | 1,420 (12) | 1,002 (3) | 6,307 (22) | 4,959 (11) | 8,204 (6) | 22,547 (8) |
| HbA1c, %* | 7.9 (1.6) | 8.2 (1.8) | 7.8 (1.7) | 8.1 (1.7) | 8.7 (2) | 8.2 (1.8) |
| HbA1c, mmol/mol† | 63 | 66 | 62 | 65 | 72 | 66 |
| HbA1c ≥7.5% (58 mmol/mol), n (% of n2) | 470 (54) | 377 (60) | 1,846 (49) | 1,940 (59) | 3,380 (68) | 8,231 (59) |
| HbA1c ≥8% (64 mmol/mol), n (% of n2) | 335 (38) | 280 (44) | 1,290 (34) | 1,451 (44) | 2,780 (56) | 6,286 (45) |
| GLP-1RA as third ADD, n (% of n2) | 84 (8) | 383 (6) | 842 (17) | 677 (8) | 2,065 (9) | |
| INS as third ADD, n (% of n2) | 262 (18) | 703 (11) | 849 (17) | 4,012 (49) | 5,931 (26) | |
| TZD as third ADD, n (% of n2) | 61 (4) | 48 (5) | 273 (6) | 510 (6) | 924 (4) | |
| DPP-4i as third ADD, n (% of n2) | 488 (34) | 269 (27) | 2,199 (35) | 2,436 (30) | 5,561 (25) | |
| SU as third ADD, n (% of n2) | 390 (27) | 521 (52) | 2,829 (45) | 2,456 (50) | 6,450 (29) | |
| SGLT2i as third ADD, n (% of n2) | 205 (14) | 66 (7) | 109 (2) | 464 (9) | 373 (5) | 1,228 (5) |
| . | GLP-1RA . | INS . | TZD . | DPP-4i . | SU . | All . |
|---|---|---|---|---|---|---|
| N | 11,431 | 36,337 | 28,841 | 46,822 | 149,109 | 278,188 |
| Follow-up from second ADD initiation, years* | 3.85 (2.24) | 3.56 (2.09) | 5.40 (2.66) | 3.37 (1.81) | 4.09 (2.35) | 4.02 (2.33) |
| Initiated third ADD, n (% of N) | 5,942 (52) | 10,677 (29) | 18,788 (65) | 23,840 (51) | 81,980 (55) | 144,106 |
| Initiated INS, n (% of N) | 3,285 (29) | 8,223 (29) | 9,633 (21) | 45,293 (30) | 67,812 | |
| Restricted mean time to a third ADD, years§ | 4.23 (4.14, 4.32) | 6.15 (6.09, 6.21) | 3.53 (3.49, 3.58) | 4.12 (4.07, 4.17) | 3.91 (3.88, 3.93) | 4.18 (4.17, 4.20) |
| Restricted mean time to INS, years§ | 6.58 (6.49, 6.67) | 6.82 (6.78, 6.87) | 7.14 (7.09, 7.18) | 6.26 (6.23, 6.28) | 6.51 (6.49, 6.53) | |
| Added third ADD | ||||||
| n1 (% of N) | 4,522 (40) | 9,675 (27) | 12,481 (43) | 18,881 (40) | 73,776 (49) | 121,559 (44) |
| HbA1c, %* | 8.2 (1.7) | 8.9 (2) | 8.1 (1.8) | 8.5 (1.8) | 8.6 (1.7) | 8.5 (1.8) |
| HbA1c, mmol/mol† | 66 | 74 | 65 | 69 | 70 | 69 |
| HbA1c ≥7.5% (58 mmol/mol), n (% of n1) | 1,798 (61) | 4,953 (74) | 4,102 (55) | 8,968 (69) | 32,611 (72) | 53,100 (69) |
| HbA1c ≥8% (64 mmol/mol), n (% of n1) | 1,364 (47) | 4,160 (62) | 3,101 (42) | 6,974 (54) | 26,231 (58) | 42,330 (55) |
| GLP-1RA as third ADD, n (% of n1) | 2,125 (22) | 1,532 (12) | 1,643 (9) | 5,662 (8) | 11,230 (9) | |
| INS as third ADD, n (% of n1) | 2,356 (52) | 3,338 (27) | 5,472 (29) | 20,483 (28) | 32,447 (27) | |
| TZD as third ADD, n (% of n1) | 241 (5) | 688 (7) | 1,425 (8) | 19,010 (26) | 21,472 (18) | |
| DPP-4i as third ADD, n (% of n1) | 481 (11) | 2,488 (26) | 3,804 (30) | 25,216 (34) | 32,696 (27) | |
| SU as third ADD, n (% of n1) | 865 (19) | 3,090 (32) | 3,048 (24) | 7,556 (40) | 14,844 (12) | |
| SGLT2i as third ADD, n (% of n1) | 521 (12) | 938 (10) | 138 (1) | 2,399 (13) | 2,077 (3) | 6,095 (5) |
| Switched to third ADD | ||||||
| n2 (% of N) | 1,420 (12) | 1,002 (3) | 6,307 (22) | 4,959 (11) | 8,204 (6) | 22,547 (8) |
| HbA1c, %* | 7.9 (1.6) | 8.2 (1.8) | 7.8 (1.7) | 8.1 (1.7) | 8.7 (2) | 8.2 (1.8) |
| HbA1c, mmol/mol† | 63 | 66 | 62 | 65 | 72 | 66 |
| HbA1c ≥7.5% (58 mmol/mol), n (% of n2) | 470 (54) | 377 (60) | 1,846 (49) | 1,940 (59) | 3,380 (68) | 8,231 (59) |
| HbA1c ≥8% (64 mmol/mol), n (% of n2) | 335 (38) | 280 (44) | 1,290 (34) | 1,451 (44) | 2,780 (56) | 6,286 (45) |
| GLP-1RA as third ADD, n (% of n2) | 84 (8) | 383 (6) | 842 (17) | 677 (8) | 2,065 (9) | |
| INS as third ADD, n (% of n2) | 262 (18) | 703 (11) | 849 (17) | 4,012 (49) | 5,931 (26) | |
| TZD as third ADD, n (% of n2) | 61 (4) | 48 (5) | 273 (6) | 510 (6) | 924 (4) | |
| DPP-4i as third ADD, n (% of n2) | 488 (34) | 269 (27) | 2,199 (35) | 2,436 (30) | 5,561 (25) | |
| SU as third ADD, n (% of n2) | 390 (27) | 521 (52) | 2,829 (45) | 2,456 (50) | 6,450 (29) | |
| SGLT2i as third ADD, n (% of n2) | 205 (14) | 66 (7) | 109 (2) | 464 (9) | 373 (5) | 1,228 (5) |
n1, number of subcohort 2 patients for each drug class who added a third ADD; n2, number of subcohort 2 patients for each drug class who switched to a third ADD. *Mean (SD);
†mean;
§mean (95% CI).
‡Subcohort 2: those with MET as first-line treatment, who initiated second ADD, with a minimum of 1 year of follow-up post–second drug initiation.