This review highlights the efficacy and safety of Gla-100 in comparison to other insulin preparations in initiation and intensification strategies in type 2 diabetes mellitus (T2DM). |
Initiation of Gla-100 in insulin-naïve patients with T2DM failing oral therapies resulted in better glucose-lowering outcomes than premixed insulins and showed comparable results to neutral protamine Hagedorn (NPH), second-generation basal insulins, co-formulations, as well as other first-generation basal insulins. |
Most of the studies showed that Gla-100 initiation in insulin-naïve people with T2DM is associated with a lower risk of overall hypoglycemic events compared to other insulin molecules except for second-generation basal insulins. |
Intensification of insulin therapy with Gla-100-based regimens in most of the studies showed significantly better glucose-lowering outcomes against insulin detemir (IDet), comparable results to NPH, second-generation basal insulins, co-formulations, and against premixed insulins. |
Most of the Gla-100 intensification studies showed comparable overall hypoglycemia risk with all other insulin regimens, but a significantly lower risk of nocturnal hypoglycemia vs. NPH and premixed insulins and a significantly greater risk compared to second-generation basal insulins. |
Introduction
Methods
Search Strategy
Inclusion and Exclusion Criteria
Screening of Eligible Studies
Outcomes
Data Extraction
Results
Study Search
Author (year) | Study design; n (total) | Study duration in monthsa (weeks) | Intervention; n (each arm) | Age (years), mean (SD if available) | Sex (female), n (if available) (%) | Disease duration (years), mean (SD if available) |
---|---|---|---|---|---|---|
Gla-100 vs. NPH insulin | ||||||
Fiesselmann, 2016 [14] | Retrospective study; 1917 | 6–9 (24) | Gla-100 OD + OADs; 285 (PSM matched cohort) | 63.7 (11.2) | 133 (47.4) | 5.5 (2.6) |
Insulin NPH OD / BD + OADs; 285 (PSM matched cohort) | 64.4 (10.7) | 131 (46.5) | 5.3 (2.6) | |||
Home PD, 2014 [15] | RCT; 701 | 9–12 (38) | Gla-100 + OADs; 352 | 57.3 (8.3) | 198 (56.2) | 9.1 (5.5) |
Insulin NPH + OADs; 349 | 57.2 (7.8) | 195 (55.9) | 9.4 (5.7) | |||
Delgado E, 2012 [16] | Retrospective study; 1482 | 3–12 (17–39 [time of switch from NPH to Gla-100 to the study visit]) | Gla-100 OD + OADs; 976 | 61.9 (11) | 483 (49.5) | 10.2 |
Insulin NPH OD / BD + OADs; 506 | 64.3 (11.4) | 276 (54.5) | 12.4 | |||
Hsia SH, 2011 [17] | RCT; 85 | 6–9 (28) | Gla-100 HS + OADs; 30 | 50.3 (11.2) | 15 (50.0) | 9 (5.9) |
Gla-100 morning + OADs; 25 | 53 (8.6) | 13 (52.0) | 9.5 (5.2) | |||
Insulin NPH + OADs (previous); 30 | 53.2 (7.7) | 21 (70.0) | 7.8 (4.2) | |||
Mu P, 2011 [18] | RCT; 250 | 3–6 (12) | Gla-100 OD + OADs; 124 | 40.3 (8.5) | 69 (55.6) | 4.9 (2.6) |
Insulin NPH + OADs; 126 | 40.6 (8.3) | 74 (58.7) | 4.7 (2.4) | |||
Mattia, 2009 [19] | RCT; 20 | 3–6 (15) | Sequence A (Gla-100 followed by NPH insulin); 9 | 59.4 (8.2) | 6 (30.0) | – |
Sequence B (NPH insulin followed by Gla-100); 11 | ||||||
Pan, 2007 [20] | RCT; 443 | 6–9 (28) | Gla-100 + glimepiride 3 mg; 220 | 55.6 (8.4) | 131 (59.6) | 10.3 (6.3) |
Insulin NPH + glimepiride 3 mg; 223 | 56.6 (8.7) | 124 (55.6) | 10 (5.4) | |||
Yki-Jarvinen, 2006 [21] | RCT; 110 | 9–12 (40) | Gla-100 + metformin; 61 | 56.0 (1.0) | 23 (38) | 9 (1) |
Insulin NPH + metformin; 49 | 57 (1) | 17 (35) | 9 (1) | |||
Eliaschewitz, 2006 [22] | RCT; 481 | 6–9 (28) | Gla-100 + glimepiride 4 mg; 231 | 56.1 (9.9) | 132 (57.1) | 10.3 (6.4) |
Insulin NPH + glimepiride 4 mg; 250 | 57.1 (9.6) | 155 (62.0) | 10.8 (6.4) | |||
Shi, 2004 [23] | RCT; 56 | 6–9 (24) | Gla-100 + glipizide GITS 5 mg; 42 | 60.13 (7.14) | 20 (48) | 7.13 (3.13) |
Insulin NPH + glipizide GITS 5 mg; 14 | 62.15 (5.16) | 410 (72) | 7.11 (4.11) | |||
Benedetti, 2003 [24] | RCT; 570 | > 12 (56) | Gla-100 OD + OADs; 289 | 59.6 (9.3) | 135 (46.7) | 10.2 (6.2) |
Insulin NPH OD / BD + OADs; 281 | 59.4 (9.1) | 129 (45.1) | 10.5 (6) | |||
Riddle, 2003 [25] | RCT; 756 | 6–9 (28) | Gla-100 + OADs; 367 | 55 (9.5) | 166(45) | 8.4 (5.55) |
Insulin NPH + OADs; 389 | 56 (8.9) | 171(44) | 9 (5.57) | |||
Yki-Jarvinen, 2000 [26] | RCT; 422 | > 12 (56) | Gla-100 + OADs; 214 | 59 (1) | 97 (45) | 10 (1) |
Insulin NPH + OADs; 208 | 59 (1) | 98 (47) | 10 (1) | |||
Gla-100 vs. premixed insulins | ||||||
Petrovski, 2018 [27] | Observational, prospective, switch study; 1041 | 6–9 (24) | Human/analog premixed alone switched to Gla-100 OD ± OADs | 61.8 (9.31) | 606 (58.2) | 11.4 (6) |
Zhang, 2017 [28] | Observational, prospective, switch study; 1847 | 3–6 (16) | Human/analog premixed ± OADs switched to Gla-100 OD + OADs | 56.3 (11) | 816 (44.2) | 8.5 (6.2); duration of prior premixed use: 24.5 (27.4) months |
Cao, 2017 [29] | RCT; 65 | 3–6 (16) | Gla-100 OD + 100 mg; 33 | 52.1 (9.6) | 15 (46.6) | 5.7 (3.6) |
Insulin aspart 30 BD; 32 | 49.8 (11.2) | 16 (49.8) | 6.4 (4.1) | |||
Sehgal S, 2015 [7] | Retrospective study; 337 | > 12 (52) | Human NPH + OADs (previous); 273 | 55.7 (13.9) | 134 (49.1) | 10.6 (6.7) |
Gla-100 OD + OADs (previous); 24 | 59.2 (16.5) | 9 (37.5) | 9.2 (6.6) | |||
Biphasic human premixed insulin + OADs (previous); 42 | 56.7 (11.4) | 21 (50.0) | 12 (9.8) | |||
Zhang Y, 2014 [12] | Observational, prospective, switch study; n = 70 | 3–6 (20) | Human/analog premixed insulin alone switched to Gla-100 OD ± OADs | 59.95 (10.21) | 37 (52.8) | 7.78 (2.95); Premixed therapy duration—3.21 (0.87) |
Sun, 2014 [11] | RCT; 188 | 6–9 (32) | Gla-100 + acarbose TID; 94 | 68.2 (6.6) | 48 (51.1) | 7.5 (4) |
Novolin 30R (Human) BD; 94 | 70.3 (5.7) | 51 (54.2) | 6.8 (2.8) | |||
Sakharova OV 2013 [30] | RCT; 14 | 3–6 (24) | Gla-100 + OADs | 61 (12) | 5 (35.7) | 11 (6) |
Lispro mix 75/25 + OADs | - | - | - | |||
Kalra, 2010 [31] | RCT; 155 | 6–9 (30) | Gla-100 + MET + SU (glimepiride); 79 | 51.58 (10.14) | 48 (61) | 8.6 (5.79) |
BI-Asp 30 + MET + SU (glimepiride); 76 | 51.95 (9.07) | 46 (61) | 8.62 (6.17) | |||
Strojek, 2009 [32] | RCT; 469 | 6–9 (30) | Gla-100 + MET + SU (glimepiride); 231 | 56.1 (10) | 140 (58.8) | 9.5 (6.1) |
BI-Asp 30 + MET + SU (glimepiride); 238 | 55.9 (9.7) | 123 (53.2) | 9.1 (5.8) | |||
Buse, 2009 [33] | RCT; 2091 | 6–9 (26) | Gla-100 + OADs (previous); 1046 | 57 (10) | 493(47.2) | 9.3 (5.9) |
Lispro mix 75/25 + OADs (previous); 1045 | 57 (10) | 494(47.2) | 9.7 (6.3) | |||
Schiel, 2007 [34] | RCT; 52 | 3–6 (20) | Grp A: Gla-100 OD + glimepiride OD; 17 | 61.7 (10.7) | 9 (53) | 15.3 (8.4) |
Grp B: Gla-100 OD + glimepiride OD + MET BD; 18 | 65.4 (8.5) | 8 (44) | 14.2 (8) | |||
Grp C: Human premixed insulin 75/25 or 70/39; 17 | 69.8 (6.4) | 8 (47) | 16.3 (6.7) | |||
Robbins, 2007 [35] | RCT; 315 | 6–9 (32) | Gla-100 OD + MET BD; 158 | 58.1 (8.9) | 80 (50.6) | 12.5 (6.8) |
Lispro mix 75/25 BD + MET BD; 157 | 57.4 (9.2) | 78(49.7) | 11.3 (5.8) | |||
Raskin, 2007 [36] | RCT; 157 | 6–9 (28) | Gla-100 OD + MET; 78 | 51.7 (9.8) | 36 (46.2) | - |
BiAsp 70/30 BD + MET; 79 | 52 (11) | 38 (48.1) | - | |||
Jacober, 2006 [37] | RCT; 60 | 6–9 (32) | Sequence A (16 weeks Gla-100 followed by 16 weeks premixed insulin 50/50 lispro mix pre-breakfast and 25/75 lispro mix pre-dinner); 29 | 54.9 (10) | 26 (43.3) | 8.4 (4.9) |
Sequence B (16 weeks premixed insulin 50/50 lispro mix pre-breakfast and 25/75 lispro mix pre-dinner followed by 16 weeks Gla-100); 31 | ||||||
Kazda, 2006 [10] | RCT; 159 | 6–9 (26) | Lispro 50% TID; 52 | 60.4 (8.6) | 20 (38.4) | 5.3 (2.8) |
Lispro mid-mixture (50% lispro / 50% NPL); 54 | 58.7 (10.2) | 22 (40.74) | 5.9 (3) | |||
Gla-100 OD; 53 | 59.1 (9.6) | 30 (56.60) | 5.5 (2.8) | |||
Roach, 2006 [13] | RCT; 20 | 6–9 (25) | Sequence A—Gla-100 OD + OADs followed by insulin lispro 25/75 BD + OADs; n = 10 | 53.5 (10.7) | 10 (50) | - |
Sequence B—Insulin lispro 25/75 BD + OADs followed by Gla-100 OD + OADs; 10 | ||||||
Bullano, 2006 [38] | Retrospective study; 2315 | – | Gla-100 group; n = 1212 | 52 (14) | 548 (46) | 13.4 (7.8) |
Premixed insulin group (70 NPH or long-acting insulin: 30 units of short-acting or rapid-acting insulin); 1103 | 55 (13) | 539 (48.9) | 14 (8.5) | |||
Janka, 2005 [39] | RCT; 364 | 6–9 (28) | Gla-100 + OADs (glimepiride + metformin); 177 | 60.9 (8.7) | 69 (39) | 9.9 (7.3) |
Human premixed insulin (30% regular, 70% NPH insulin; insulin actraphane HM 30/70); 187 | 60.4 (9.1) | 80 (43) | 9.9 (6.4) | |||
Raskin 2005 [40] | RCT; 209 | 6–9 (28) | BiAsp 70/30 BD + OADs; 117 | 52.6 (10.6) | 47 (40.1) | 9.5 (5.9) |
Gla-100 OD + OADs; 116 | 52.3 (9.8) | 44 (37.9) | 8.9 (4.8) | |||
Malone, 2004 [41] | RCT; 105 | 9–12 (40) | Sequence A (Gla-100 HS + MET 1500–2550 mg/day followed by lispro mix 75/25 + MET 1500–2550 mg/day) | 55.3 (9.5) | 20 (37.7) | 9.8 (7.4) |
Sequence B (lispro mix 75/25 + MET 1500–2550 mg/day followed by Gla-100 HS + MET 1500–2550 mg/day) | 54.5 (11.4) | 19 (36.5) | 8.1 (5.8) | |||
Gla-100 vs. Second-generation basal insulins | ||||||
Bailey, 2019 [42] | Retrospective cohort study; 3012 | 6–9 (26) | Gla-300 OD + OADs; 1004 | 60.2 (12.3) | 481 (48) | - |
Gla-100 OD + OADs; 2008 | 60.5 (12.3) | 928 (46) | - | |||
Gupta, 2018 [43] | Retrospective cohort study; 553 | 6–9 (26) | Gla-100 OD + OADs; 92 | 54.4 (13.1) | 36 (39.1) | 11.1 (8.6) |
Gla-300 OD + OADs; 298 | 53.6 (11.9) | 142 (47.7) | 10.9 (9.5) | |||
Switched to Gla-300 OD + OADs; 163 | 56.3 (10.3) | 67 (41.1) | 13.3 (8.1) | |||
Nakanishi, 2018 [6] | Retrospective observational switch study; 122 | 3–6 (12) | Switched to Gla-300 OD ± OADs; 62 | 62.1 (14.7) | 26 (42) | – |
Gla-100 OD ± OADs; 60 | 70.3 (9.2) | 27 (45) | – | |||
Marso, 2017 [44] | RCT; 7637 | > 12 (104 [30 days follow-up]) | IDeg OD ± OADs; 3818 | 64.9 (7.3) | 1422 (37.2) | 16.6 (8.8) |
Gla-100 OD ± OADs; 3819 | 65 (7.5) | 1437 (37.6) | 16.2 (8.9) | |||
Wysham, 2017 [45] | RCT; 721 | > 12 (65) | Sequence B- IDeg OD ± OADs followed by Gla-100 ± OADs; 361 | 61.5 (10.7) | 169 (47) | 14.2 (8.3) |
Sequence A—Gla-100 OD ± OADs followed by IDeg OD ± OADs; 360 | 61.2 (10.3) | 169 (47) | 13.9 (8) | |||
Pan, 2016 [46] | RCT; 833 | 6–9 (26) | IDeg 100 OD + MET; 555 | 55.9 (9.7) | 256 (46.1) | 7.55 (5.28) |
Gla-100 OD + MET; 278 | 56.6 (9.2) | 146 (52.5) | 8.26 (5.45) | |||
Ghoshal, 2016 [47] | Retrospective cohort study; 64 | 6–9 (24) | IDeg 100 OD + OADs; 33 | 56.09 (13.59) | 14 (42.4) | 12.15 (7.19) |
Gla-100 OD + OADs; 31 | 58.97 (11.32) | 13 (42) | 9.93 (3.98) | |||
Terauchi, 2016 [8] | RCT; 241 | 6–9 (26) | Gla-300 OD ± OADs; 121 | 61.1 (10.8) | 44 (36.36) | 14 (8) |
Gla-100 OD ± OADs; 120 | 60.5 (12) | 50 (41.67) | 13.9 (8.7) | |||
Bolli, 2015 [48] | RCT; 878 | 6–9 (26) | Gla-300 OD + OADs—SUs / glinides; 439 | 58.2 (9.9) | 186 (42) | 10.1 (6.5) |
Gla-100 OD + OADs—SUs / glinides; 439 | 57.2 (10.3) | 185 (42) | 9.6 (6.2) | |||
Yki-Jarvinen, 2014 [49] | RCT; 811 | 6–9 (26) | Gla-300 OD ± OADs; 404 | 57.9 (9.1) | 217 (53.7) | 12.7 (7.1) |
Gla-100 OD ± OADs; 407 | 58.5 (9.2) | 222 (54.5) | 12.5 (7.0) | |||
Gough SC, 2013 [50] | RCT; 457 | 6–9 (26) | IDeg -200 + MET ± DPP-4; 228 | 57.8 (9) | 109 (47.8) | 8.4 (6.7) |
Gla-100 OD + MET ± DPP-4 inhibitors; 229 | 57.3 (9.4) | 105 (45.9) | 8 (5.6) | |||
Onishi Y 2013 [51] | RCT; 435 | 6–9 (26) | IDeg OD + OADs—DPP-4 inhibitors; 289 | 58.8 (9.8) | 131 (45.3) | 11.8 (6.5) |
Gla-100 OD + OADs—DPP-4 inhibitors; 146 | 58.1 (10.1) | 71 (48.6) | 11.1 (6.5) | |||
Meneghini L 2013 [52] | RCT; 687 | 6–9 (26) | IDeg OD Flex; 229 | 56.2 (10.3) | 94 (41) | 10.8 (6.9) |
IDeg OD in morning; 228 | 56.5 (9.6) | 104 (46) | 10.3 (6.7) | |||
Gla-100 OD; 230 | 56.7 (8.8) | 119 (52.0) | 10.8 (6.4) | |||
Zinman B, 2012 [53] | RCT; 1030 | > 12 (52) | IDeg -100 + MET ± DPP-4; 257 | 59.3 (9.7) | 302 (39.1) | 9.4 (6.3) |
Gla-100 OD + MET ± DPP-4 inhibitors; 773 | 58.7 (9.9) | 90 (35.0) | 8.6 (5.7) | |||
Gla-100 vs. Co-formulations | ||||||
Kumar, 2017 [54] | RCT; 463 | 6–9 (26) | IDegAsp OD + metformin ± pioglitazone ± dipeptidyl peptidase- 4 inhibitors; 233 | 57.8 (9.5) | 41.3 | 11.6 (6.8) |
Gla-100 OD + metformin ± pioglitazone ± dipeptidyl peptidase- 4 inhibitors; 233 | 58.4 (10.1) | 45.5 | 11.4 (7.3) | |||
Kumar, 2016 [55] | RCT; 529 | > 12 (53) | IDegAsp OD + MET; 266 | 57.4 (9.0) | 53 | 8.7 (6.1) |
Gla-100 OD + MET; 263 | 56.4 (9.2) | 48.3 | 9.6 (6.1) | |||
Onishi 2013 [56] | RCT; 296 | 6–9 (26) | IDegAsp + OADs minus DPP-4 inhibitors / SU / glinides; 147 | 60 (10.0) | 57 (39.0) | 10.9 (7.3) |
Gla-100 OD + OADs minus DPP-4 inhibitors / SU / Glinides; 149 | 61 (9.6) | 51 (34.0) | 12.4 (8.6) | |||
Gla-100 vs. other basal insulins | ||||||
Cander S, 2014 [57] | RCT; 64 | 3–6 (12) | IDet OD + MET + SU; 22 | 57 | 15 (68) | 6.5 |
IDet BD + MET + SU; 22 | 54 | 7 (32) | 7 | |||
Gla-100 OD + MET + SU; 20 | 59 | 13 (65) | 7 | |||
Odawara M, 2014 [58] | Prospective, observational study; 4219 | 6–9 (24) | Gla-100 OD + OADs (insulin-naïve); 3732 | 62.6 (12.1) | 1495 (40) | – |
Gla-100 OD + OADs (insulin non-naïve); 487 | 64 (12.1) | 239 (49) | – | |||
Wei W, 2014 [59] | Retrospective, observational switch study; 5291 | 3–6 (12) | Cohort 2—Det-C Impact (Det OD continued); 780 | 60.8 (11.8) | 388 (49.7) | – |
Cohort 1—Det-S Impact (Det OD switched); 536 | 53.8 (11.7) | 262 (48.9) | – | |||
Cohort 1—Gla-C Impact (Gla-100 OD continued); 2668 | 53.5 (11.8) | 1251 (46.9) | – | |||
Cohort 1—Det-S Humana (Det OD switched); 256 | 72.6 (5.4) | 143 (55.9) | – | |||
Cohort 1—Gla-C Humana (Gla-100 OD continued); 1262 | 73 (5.6) | 692 (54.8) | – | |||
Cohort 2—Gla-S Impact (Gla-100 OD switched); 419 | 60.9 (11.7) | 222 (53.0) | – | |||
Meneghini L, 2013 [60] | RCT; 453 | 6–9 (28) | Det OD + MET; 226 | 57.3 (10.2) | 57 | 8 (5.6) |
Gla-100 OD + MET; 227 | 57.3 (10.3) | 56 | 8.4 (6.6) | |||
Esposito, 2008 [61] | RCT; 110 | 9–12 (40) | Gla-100 OD + OADs minus night time SU, replaced with MET | 54.9 (6.9) | 26 (47.3) | 8.2 (5.3) |
Human NPL OD + OADs minus night time SU, replaced with MET | 53.8 (7.1) | 27 (49.1) | 7.8 (5.4) | |||
Rosenstock, 2008 [9] | RCT; 582 | > 12 (52) | IDet OD + OADs; 291 | 58.4 (10.2) | 125 (42.95) | 9.1 (6.1) |
Gla-100 OD + OADs; 291 | 59.4 (9.6) | 120 (41.23) | 9.1 (6.4) | |||
Malone, 2005 [62] | RCT; 97 | 9–12 (38) | Seq A—Gla-100 OD + MET followed by lispro mix 75/25 BD; 47 | 59.63 (8.03) | 29 (62.0) | 11.9 (6.27) |
Seq B—lispro mix 75/25 BD + MET followed by Gla-100 OD; 50 | 59.18 (8.58) | 25 (50.0) | 13.52 (8.18) |
Author (year) | Study design | Study duration in months (weeks)a | Intervention | Age (years), mean (SD) | Sex (female), N (if available) (%) | Disease duration (years), mean (SD) | Duration of prior insulin therapy (years), mean (SD) |
---|---|---|---|---|---|---|---|
Gla-100 vs. NPH | |||||||
Betonico, 2019 [72] | RCT; 34 | 9–12 (48) | Sequence A- Gla-100 OD + insulin lispro TID for 24 weeks followed by insulin NPH + lispro TID; 16 | 63 (7.0) | 4 (25.0) | 19 (11.6) | – |
Sequence B- Insulin NPH + insulin lispro TID for 24 weeks followed by Gla-100 OD + lispro TID; 18 | 60 (8.7) | 7 (39.0) | 19 (7.0) | – | |||
Rosenstock, 2001 [73] | RCT; 518 | 6–9 (32) | Gla-100 OD ± premeal regular insulin; 259 | 59.5 (9.7) | 109 (42.1) | 13.4 (8.3) | 8.4 (6.9) |
NPH insulin OD / BD ± premeal regular insulin; 259 | 59.2 (9.9) | 98 (37.8) | 14.1 (9) | 8.3 (7.6) | |||
Gla-100 vs. premixed | |||||||
Aschner, 2015 [74] | RCT; 923 | 6–9 (26) | Gla-100 OD + glulisine OD before main meal + MET ± SU; 462 | 56.7 (9.0) | 231 (50.0) | 9.1 (6.0) | – |
Premixed insulin BD MET ± SU; 461 | 55.8 (9.5) | 221 (47.9) | 8.8 (5.8) | – | |||
Tinahones, 2014 [75] | RCT; 476 | 6–9 (26) | Insulin lispro mix BD + MET ± pioglitazone; 236 | 57.4 (9.9) | 120 (51.8) | 12.2 (7.7) | – |
Gla-100 OD + insulin lispro OD + MET ± pioglitazone; 240 | 57.7 (9.1) | 142 (59.1) | 11.3 (6.8) | – | |||
Ito H, 2014 [71] | Prospective cohort study; 27 | 3–6 (16) | Human premixed insulin 50/50 switched to Gla-100 OD + glulisine BD | 62 (16.0) | 8 (29.6) | 14 (8.0) | 4 (3.8) |
Jain, 2010 [67] | RCT; 383 | 6–9 (36) | Gla-100 OD + mealtime lispro TID; 195 | 59.9 (9.6) | 94 (48.2) | 12 (7.3) | – |
Insulin lispro mix 50/50 TID; 188 | 58.9 (8.8) | 102 (54.3) | 11.4 (5.6) | – | |||
Rosenstock, 2008 [76] | RCT; 374 | 6–9 (24) | Premixed TID (lispro mix 50:50) + OADs (minus SU + glinides); 187 | 55.4 (9.8) | 88 (47.0) | 10.9 (6.3) | – |
Gla-100 OD + insulin lispro TID + OADs (minus SU + glinides); 187 | 54 (9.2) | 89 (48.0) | 11.2 (6.2) | – | |||
Joshi, 2005 [70] | Prospective observational cohort study; 145 | 3–6 (12) | Premixed insulin analog (NovoMix 30) BD; 114 | 52.41 (10.04) | 38 (33.3) | 9.53 (5.08) | – |
Gla-100 OD + insulin aspart TID; 31 | 51.1 (14.04) | 7 (22.5) | 11.98 (9.01) | – | |||
Fritsche 2010 [64] | RCT; 310 | > 12 (52) | Gla-100 OD + insulin glulisine TID; 153 | 60.2 (7.5) | 70 (45.8) | 12.8 (5.8) | 5 (3.7) |
Premixed BID; 157 | 60.9 (7.8) | 82 (52.2) | 12.5 (6.8) | 4.7 (3.8) | |||
Levin, 2011 [77] | Randomized pragmatic trial; 197 | 6–9 (36) | Gla-100 OD + insulin glulisine TID; 106 | 56.36 (12.44) | 56 (52.8) | 13.1 (8.78) | – |
Premixed BID; 91 | 55.92 (9.87) | 51 (56) | 12.9 (8.04) | – | |||
Bowering, 2012 [78] | RCT; 433 | 9–12 (48) | Premixed TID stepwise (lispro mix 75:25) + metformin ± sulfonylurea)); 211 | 56.68 (8.03) | 118 (55.9) | 10.6 (6.18) | – |
Gla-100 OD + insulin lispro TID (stepwise fashion) + metformin; 212 | 56.29 (9.35) | 107 (50.5) | 10 (5.54) | – | |||
Miser, 2010 [63] | RCT; 744 | 6–9 (24) | Intensification arm – A: Premixed TID (lispro mix 75:25) + OADs (minus sulfonylurea)); 200 | 55.9 (10.1) | 92 (46) | 8.9 (6) | – |
Intensification arm – A: Gla-100 OD + insulin lispro TID + OADs (minus sulfonylureas); 199 | 58.2 (9.7) | 97 (49) | 9.3 (5.8) | – | |||
Intensification arm – B: Premixed TID (lispro mix 50:50) + OADs (minus sulfonylurea)); 174 | 55.4 (10) | 83 (48) | 10 (6.7) | ||||
Intensification arm – B: Gla-100 OD + insulin lispro TID + OADs (minus sulfonylureas); 171 | 54.5 (9.1) | 86 (50) | 9.6 (6) | ||||
Riddle, 2014 [66] | RCT; 588 | > 12 (60) | Gla-100 OD + insulin glulisine OD + OADs; 194 (G + 1) | 53.08 (9.08) | 106 (56.4) | 9.0 (5.72) | – |
Gla-100 OD + insulin glulisine TID + OADs; 194 (G + 3) | 53.08 (9.08) | 106 (56.4) | 9.4 (6.8) | – | |||
Premixed BD (insulin aspart 70/30 BID) + OADs; 194 (PM 2 +) | 53.7 (10.7) | 109 (56.2) | 9.5 (5.88) | – | |||
Vora, 2015 [65] | RCT; 335 | 6–9 (24) | Gla-100 OD + insulin glulisine OD + metformin; 170 | 61.6 (8) | 47 (27.6) | 12.9 (6.2) | – |
Premixed BD (insulin aspart 70/30 BID) + metformin; 164 | 61.6 (8.9) | 45 (27.4) | 13 (6.6) | – | |||
Jia. 2015 [79] | RCT; 402 | 6–9 (24) | Gla-100 OD + insulin lispro TID + OADs; 202 | 58.1 (9.07) | 93 (46.04) | 15.3 (6.6) | – |
Premixed TID (lispro 50/50 BID + lispro 75/25 OD + OADs; 197 | 59.1 (9.1) | 95 (48.22) | 15 (6.24) | – | |||
Giugliano, 2014 [68] | RCT; 344 | 9–12 (48) | Gla-100 OD + insulin lispro TID (stepwise fashion) + OADs; 173 | 54.2 (8.6) | 92 (53) | - | – |
Premixed TID (lispro 75/25 or lispro 50/50) stepwise + OADs; 171 | 54.3 (8.9) | 84 (49) | - | – | |||
Gla-100 vs. Second-generation basal insulin | |||||||
Hollander, 2015 [80] | RCT; 757 | > 12 (78 [52 weeks main trial + 26 weeks extension period]) | IDegOD OD + aspart ± MET ± pioglitazone; 566 | 58.9 (8.6) | 249 (44.0) | 13.4 (7.2) | – |
Gla-100 OD + aspart ± MET ± pioglitazone; 191 | 58.4 (9.9) | 47.4 | 13.7 (6.8) | – | |||
Riddle, 2014 [81] | RCT; 807 | 6–9 (26) | Gla-300 OD + meal-time insulin ± MET; 403 | 60.1 (8.5) | 187 (46.29) | 15.6 (7.2) | 6.7 (4.7) |
Gla-100 OD + meal-time insulin ± MET; 403 | 59.8 (8.7) | 193 (47.89) | 16.1 (7.8) | 6.5 (4.8) | |||
Gla-100 vs. co-formulations (intensification) | |||||||
Philis-Tsimikas A, 2019 [82] | RCT; 532 | 9–12 (38) | IDegAsp OD / BD ± OADs minus SU and glinides; 267 | 58.2 (8.9) | 53.2 | 12.9 (6.9) | - |
Gla-100 OD + aspart ± OADs minus SU and glinides; 265 | 59.2 (9.1) | 48.3 | 13 (6.5) | - | |||
Gla-100 vs. other basal insulins (intensification) | |||||||
Tentolouris N, 2013 [83] | Retrospective cohort switch study; 301 | > 12 (Up to 52 weeks of treatment follow-up) | Premixed BD continued; 159 | 66.7 (9.6) | 86 (54.1) | 16 (8.6) | – |
Premixed BD switched to Gla-100 OD + rapid acting insulin; 142 | 63.2 (10.1) | 82 (57.8) | 13.5 (7.8) | – | |||
Raskin, 2009 [84] | RCT; 385 | 6–9 (26) | IDet OD + aspart ± MET ± TZDs; 254 | 55.8 (10) | 123 (48.4) | 12.5 (6.8) | – |
Gla-100 OD + aspart ± MET ± TZDs; 131 | 55.9 (11) | 52 (39.7) | 11.9 (7.4) | - | |||
Hollander, 2008 [85] | RCT; 319 | > 12 (52) | IDet OD + aspart + OADs (minus secretagogues and α-glucosidase inhibitors); 214 | 59 | 84 (39.3) | 13.6 | – |
Gla-100 OD + aspart + OADs (minus secretagogues and α-glucosidase inhibitors); 105 | 58 | 50 (47.6) | 13.4 | – |
Study and Patient Characteristics
Initiation
Author, year | Intervention | Study duration (months) | Mean HbA1c | Mean change (SD if available) | Intergroup p value | |
---|---|---|---|---|---|---|
(SD if available) | ||||||
Baseline | Post treatment | |||||
Gla-100 vs. NPH insulin | ||||||
Fiesselmann, 2016 [14] | Gla-100 OD + OADs | 6–9 | – | – | − 1.2 (1.1) | < 0.0001 |
Insulin NPH OD / BD + OADs | – | – | − 0.7 (0.9) | |||
Home PD, 2014 [15] | Gla-100 + OADs | 9–12 | 8.2 (0.8) | 7.1 (0.9) | − 1.07 (0.5) | – |
Insulin NPH + OADs | 8.2 (0.9) | 7.2 (1.0) | − 0.97 (0.5) | |||
Delgado E, 2012 [16] | Gla-100 OD + OADs | 3–12 | 8.3 (1.2) | 7.3 (0.9) | − 1 (1) | < 0.0001 |
Insulin NPH OD / BD + OADs | 7.9 (1.1) | 7.8 (1.1) | − 0.2 (0.8) | |||
Mu P, 2011 [18] | Gla-100 OD + OADs | 3–6 | 9.82 (1.56) | 6.52 (1.34) | – | < 0.05 |
Insulin NPH + OADs | 9.68 (1.73) | 7.63 (1.18) | – | |||
Hsia SH, 2011 [17] | Insulin NPH + OADs | 6–9 | 9.3 (1.6) | 7.9 (1.5) | − 1.4 (1.7) | – |
Gla-100 HS + OADs | 9.2 (1.3) | 7.9 (1.4) | − 1.3 (1.2) | |||
Mattia, 2009 [19] | Gla-100 followed by NPH | 3–6 | 9.3 (1.4) | – | − 1.7 (1.6) | – |
NPH followed by Gla-100 | 9.3 (1.4) | – | - 1.6 (1.6) | |||
Pan, 2007 [20] | Gla-100 + glimepiride 3 mg | 6–9 | 9 (0.86) | 7.90 (1.16) | − 1.1 | 0.03 |
Insulin NPH + glimepiride 3 mg | 9.05 (0.86) | 8.13 (1.19) | − 0.92 | |||
Eliaschewitz, 2006 [22] | Gla-100 + glimepiride 4 mg | 6–9 | 9.03 (1.09) | 7.65 (1.30) | − 1.38 (1.32) | – |
Insulin NPH + glimepiride 4 mg | 9.21 (0.99) | 7.78 (1.29) | − 1.44 (1.33) | |||
Jarvinen, 2006 [21] | Gla-100 + metformin | 9–12 | 9.13 (0.15) | 7.14 (0.12) | − 1.99 | – |
Insulin NPH + metformin | 9.26 (0.15) | 7.16 (0.14) | − 2.1 | |||
Shi, 2004 [23] | Gla-100 + glipizide GITS 5 mg | 6–9 (24) | 8.12 (2.19) | – | − 0.82 | – |
Insulin NPH + glipizide GITS 5 mg | 8.18 (3.1) | – | − 1.1 | |||
Riddle, 2003 [25] | Gla-100 + OADs | 6–9 | 8.61 (0.9) | 6.96 | − 1.65 | – |
Insulin NPH + OADs | 8.56 (0.9) | 6.97 | − 1.59 | |||
Benedetti, 2003 [24] | Gla-100 OD + OADs | > 12 | 9 (1.2) | – | − 0.46 | – |
Insulin NPH OD / BD + OADs | 8.9 (1.1) | – | − 0.38 | |||
Yki-Jarvinen, 2000 [26] | Gla-100 + OADs | > 12 | 9.1 (1) | 8.34 (0.09) | − 0.76 | p < 0.001 |
Insulin NPH + OADs | 8.9 (1) | 8.24 (0.09) | − 0.66 | |||
Gla-100 vs. premixed insulin | ||||||
Petrovski, 2018 [27] | Human/A-log premixed alone switched to Gla-100 OD ± OADs | 6–9 | 9.5 (1.6) | 7.5 (1.1) | – | < 0.05 |
Cao Y, 2017 [29] | Gla-100 OD + sitagliptin 100 mg | 3–6 | 8.07 (0.91) | – | − 1.14 | – |
Insulin aspart 30 BD | 8.23 (0.81) | – | − 0.94 | |||
Zhang, 2017 [28] | Human / A-log premixed ± OADs switched to Gla-100 OD + OADs | 3–6 | 7.8 (1.2) | 7 (1) | − 0.8 (1.2) | < 0.0001 |
Sehgal S, 2015 [7] | Human NPH + OADs | > 12 | 10.3 | 8.8 | − 1.5 | – |
Gla-100 OD + OADs | 10.9 | 8.5 | − 2.4 | – | ||
Biphasic human premixed insulin + OADs | 10.7 | 8.6 | − 2.1 | – | ||
Sun, 2014 [11] | Novolin 30R (Human) BD; n = 94 | 6–9 | 8.65 (0.43) | 7.11 (0.50) | – | – |
Gla-100 + acarbose TID | 8.62 (0.44) | 7.23 (0.61) | – | |||
Zhang Y, 2014 [12] | Human / A-log premixed alone switched to Gla-100 OD ± OADs | 3–6 | 8.28 (1.24) | 6.83 (1.09) | – | 0.01 |
Sakharova O V 2013 [30] | Lispro mix 75/25 + OADs | 3–6 | 9.7 (2.4) | 7.2 (0.7) | − 2.5 (2.4) | 0.009 |
Gla-100 + OADs | 9.7 (2.4) | 8 (1.1) | − 1.7 (2.07) | |||
Kalra, 2010 [31] | BI-Asp 30 + MET + SU (glimepiride) | 6–9 | 8.47 (1.04) | 7.25 (0.13) | − 1.22 | 0.015 |
Gla-100 + MET + SU (glimepiride) | 8.44 (1.1) | 7.60 (0.13) | − 0.87 | |||
Buse, 2009 [33] | Lispro mix 75/25 + OADs | 6–9 | 9.1 (1.3) | 7.3 (1.1) | − 1.8 (1.3) | 0.005 |
Gla-100 + OADs | 9 (1.2) | 7.2 (1.1) | − 1.7 (1.3) | |||
Strojek, 2009 [32] | BI-Asp 30 + MET + SU (glimepiride) | 6–9 | 8.5 (1) | 7.1 | – | 0.029 |
Gla-100 + MET + SU (glimepiride) | 8.5 (1.1) | 7.3 | – | |||
Grp A: Gla-100 OD + glimepiride OD | 3–6 | 8.22 (0.69) | 7.87 (0.66) | − 0.35 (0.52) | – | |
Grp B: Gla-100 OD + glimepiride OD + MET BD | 8.14 (0.9) | 7.44 (0.92) | -0.69 (0.86) | - | ||
Grp C: Human premixed insulin 75/25 or 70/39 | 8.08 (0.84) | 7.83 (1.13) | − 0.25 (1.02) | |||
Robbins, 2007 [35] | Lispro mix 75/25 BD + MET BD | 6–9 | 7.8 (0.9) | 7.1 (0.9) | − 0.7 (0.9) | < 0.001 |
Gla-100 OD + MET BD | 7.8 (1) | 7.5 (1.0) | − 0.4 (0.9) | |||
Raskin, 2007 [36] | BiAsp 70/30 BD + MET | 6–9 | 9.9 (1.5) | 7.0 (1.3) | − 2.89 (1.6) | 0.035 |
Gla-100 OD + MET | 9.9 (1.6) | 7.4 (1.3) | − 2.46 (1.6) | |||
Jacober, 2006 [37] | 16 weeks premixed insulin 50/50 lispro mix pre-breakfast and 25/75 lispro mix predinner followed by 16 weeks Gla-100 | 6–9 | 9.21 (1.33) | 7.08 (0.11) | − 1.98 (0.1) | 0.0083 |
16 weeks Gla-100 followed by 16 weeks premixed insulin 50/50 lispro mix pre-breakfast and 25/75 lispro mix predinner | 9.21 (1.33) | 7.34 (0.11) | − 1.76 (0.1) | |||
Kazda, 2006 [10] | Lispro 50% TID | 6–9 | 8.2 (1.2) | – | − 1.1 (1.1) | < 0.001 |
Lispro mid-mixture (50% lispro / 50% NPL) | 8.1 (1.2) | – | − 1.2 (1.1) | |||
Gla-100 OD | 8.1 (1.3) | – | − 0.3 (1.1) | |||
Bullano, 2006 [38] | Gla-100 | – | 9.07 (2.1) | 8.30 (1.7) | - 0.77 (1.8) | – |
Premixed insulin (70 units of NPH or long-acting insulin to 30 units of short-acting or rapid-acting insulin) | 9.23 (2.3) | 8.47 (2.2) | − 0.89 (1.9) | |||
Roach, 2006 [13] | Insulin lispro 25/75 BD + OADs followed by Gla-100 OD + OADs | 6–9 | 8.4 (1.01) | 6.9 (0.52) | – | 0.035 |
Gla-100 OD + OADs followed by insulin lispro 25/75 BD + OADs | 8.4 (1.01) | 7.3 (0.81) | – | |||
Janka, 2005 [39] | Gla-100 + OADs (glimepiride + metformin) | 6–9 | 8.85 (0.98) | 7.15 (0.90) | − 1.64 | 0.0003 |
Human premixed insulin (30% regular, 70% NPH insulin; insulin actraphane HM 30/70) | 8.83 (0.87) | 7.49 (1.09) | − 1.31 | |||
Raskin, 2005 [40] | BiAsp 70/30 BD + OADs | 6–9 | 9.7 (1.5) | 6.91 (1.17) | − 2.79 (0.11) | P < 0.01 |
Gla-100 OD + OADs | 9.8 (1.4) | 7.41 (1.24) | − 2.36 (0.11) | |||
Malone, 2004 [41] | Lispro mix 75/25 + MET 1500–2550 mg/day followed by Gla-100 HS + MET 1500–2550 mg/day | 9–12 | 8.7 (1.3) | 7.4 (1.1) | − 1.32 (1.01) | 0.003 |
Gla-100 HS + MET 1500–2550 mg/day followed by lispro mix 75/25 + MET 1500–2550 mg/day | 8.7 (1.3) | 7.8 (1.1) | − 0.93 (0.89) | |||
Gla-100 vs. second-generation basal insulin | ||||||
Bailey, 2019 [42] | Gla-300 OD + OADs | 6–9 | 9.59 (1.96) | 8.07 | − 1.52 (2.08) | 0.003 |
Gla-100 OD + OADs | 9.56 (1.94) | 8.26 | − 1.3 (2.12) | |||
Gupta, 2018 [43] | Insulin–ive patients: Started Gla-100 OD + OADs | 6–9 | 8.45 | 7.33 | − 1.12 | – |
Insulin–ive patients: Started Gla-300 OD + OADs | 8.63 | 7.42 | − 1.21 | |||
Insulin-experienced patients: Switched to Gla-300 OD + OADs | 8.5 | 7.55 | − 0.95 | |||
Nakanishi, 2018 [6] | Switched to Gla-300 ± OADs | 3–6 | 8.07 (0.97) | 7.79 (1.20) | – | – |
Gla-100 OD ± OADs | 7.55 (0.82) | 7.5 (0.73) | – | – | ||
Wysham, 2017 [45] | Sequence A—Gla-100 OD ± OADs followed by IDeg OD ± OAD | > 12 | 7.6 (1.1) | 7.08 (1.23) | – | - |
Sequence B—IDeg OD ± OADs followed by Gla-100 ± OADs | 7.6 (1.1) | 7.11 (1.23) | – | |||
Marso, 2017 [44] | IDeg OD ± OADs | > 12 | 8.44 (1.63) | 7.5 | – | – |
Gla-100 OD ± OADs | 8.41 (1.67) | 7.5 | – | |||
Pan, 2016 [46] | IDeg 100 OD + MET | 6–9 | 8.3 (0.9) | 7.0 (0.9) | − 1.3 (1.1) | – |
Gla-100 OD + MET | 8.3 (0.8) | 7.0 (0.9) | − 1.2 (1) | |||
Ghosal, 2016 [47] | IDeg 100 OD + OADs | 6–9 | 8.58 (1.35) | 7.12 (0.64) | − 1.45 (1.17) | – |
Gla− 100 OD + OADs | 8.42 (0.89) | 7.32 (0.72) | − 1.09 (0.55) | |||
Terauchi, 2016 [8] | Gla-300 OD ± OADs | 6–9 | 7.99 (0.72) | - | − 0.45 (0.06) | – |
Gla-100 OD ± OADs | 8.06 (0.77) | - | − 0.55 (0.06) | |||
Bolli, 2015 [48] | Gla-300 OD + OADs (previous)—SUs / Glinides | 6–9 | 8.49 (1.04) | 7.08 (0.96) | − 1.42 (0.05) | – |
Gla-100 OD + OADs (previous)—SUs / Glinides | 8.58 (1.07) | 7.05 (0.95) | − 1.46 (0.05) | |||
Yki-J¨arvinen, 2014 [49] | Gla-300 OD ± OADs | 6–9 | 8.26 (0.86) | 7.57 | - | – |
Gla-100 OD ± OADs | 8.22 (0.77) | 7.56 | - | |||
Gough SC, 2013 [50] | IDeg -200 + MET ± DPP-4 inhibitors | 6–9 | 8.3 (1) | - | − 1.3 (1.01) | – |
Gla-100 OD + MET ± DPP-4 inhibitors | 8.2 (0.9) | - | − 1.3 (1.01) | |||
Onishi Y 2013 [51] | IDeg OD + OADs minus DPP-4 inhibitors | 6–9 | 8.4 (0.8) | 7.2 | − 1.24 | – |
Gla-100 OD + OADs minus DPP-4 inhibitors | 8.5 (0.8) | 7.1 | − 1.35 | |||
Meneghini L 2013 [52] | IDeg OD Flex | 6–9 | 8.5 (1) | - | − 1.28 | – |
IDeg OD in morning | 8.4 (0.9) | - | − 1.07 | |||
Gla-100 OD | 8.4 (0.9) | - | − 1.26 | |||
Zinman B, 2012 [53] | IDeg -100 + MET ± DPP-4 inhibitors | > 12 | 8.2 (0.8) | 7.1 | − 1.06 (1.01) | – |
Gla-100 OD + MET ± DPP-4 inhibitors | 8.2 (0.8) | 7 | − 1.19 (0.97) | |||
Gla-100 vs. Co-formulations | ||||||
Kumar, 2017 [54] | IDegAsp OD + metformin ± pioglitazone ± dipeptidyl peptidase-4 inhibitors | 6–9 | 8.3 (0.8) | 7.3 | − 0.97 | – |
Gla-100 OD + metformin ± pioglitazone ± dipeptidyl peptidase-4 inhibitors | 8.4 (1) | 7.4 | -1 | – | ||
Kumar, 2016 [55] | Gla-100 OD + MET | > 12 | 8.9 (1) | 7.6 | − 1.34 | – |
IDegAsp OD + MET | 8.9 (0.9) | 7.5 | − 1.39 | |||
Onishi Y 2013 [56] | IDegAsp + OADs (previous) minus DPP-4 Inhibitors / SU / Glinides | 6–9 | 8.3 (0.8) | 7 (0.8) | − 1.4 (0.9) | – |
Gla-100 OD + OADs (previous) minus DPP-4 Inhibitors / SU / Glinides | 8.5 (0.8) | 7.3 (0.9) | − 1.2 (1) | |||
Gla-100 vs. other basal insulins | ||||||
Cander S, 2014 [57] | IDet OD + MET + SU | 3–6 | 9.9 | - | − 1.9 | – |
IDet BD + MET + SU | 9.3 | - | − 1.2 | |||
Gla-100 OD + MET + SU | 9.6 | - | − 1.35 | |||
Odawara M, 2014 [58] | Gla-100 OD + OADs (insulin-naïve) | 6–9 | 9.53 (1.19) | 8.07 (1.2!) | - | – |
Gla-100 OD + OADs (insulin non-naïve) | 9.08 (1.11) | 8.46 (1.39) | - | |||
Wei W, 2014 [59] | Cohort 1—Gla-C impact Gla-100 OD continued | 3–6 | 8.6 (1.7) | 8.35 | − 0.13 | < 0.05 for Gla-100 and Det comparison in favor of Gla-100 |
Cohort 1—Det-S impact (Det OD switched) | 8.7 (1.7) | 8.64 | − 0.06 | |||
Cohort 1—Gla-C Huma- (Gla-100 OD continued) | 8.2 (1.5) | 8.04 | − 0.14 | |||
Cohort 1—Det-S Huma- (Det OD switched) | 8.3 (1.5) | 8.31 | 0 | |||
Cohort 2—Det-C impact (Det OD continued) | 8.9 (1.8) | 8.54 | -− 0.68 | |||
Cohort 2—Gla-S Impact (Gla-100 OD switched) | 9.1 (1.9) | 8.34 | − 0.36 | |||
Meneghini L, 2013 [60] | IDet OD + MET | 6–9 | 7.96 (0.62) | 7.48 (0.91) | − 0.48 (0.94) | – |
Gla-100 OD + MET | 7.86 (0.58) | 7.13 (0.72) | − 0.74 (0.76) | |||
Esposito, 2008 [61] | Human NPL OD + OADs minus night-time SU, replaced with MET | 9–12 | 8.8 (0.7) | - | − 1.83 | – |
Gla-100 OD + OADs minus night-time SU, replaced with MET | 8.7 (0.7) | - | − 1.89 | |||
Rosenstock, 2008 [9] | IDet OD + OADs | > 12 | 8.64 (0.78) | 7.16 (0.08) | – | – |
Gla-100 OD + OADs | 8.62 (0.77) | 7.12 (0.08) | – | |||
Malone, 2005 [62] | Lispro mix 75/25 BD + MET followed by Gla-100 OD | 9–12 | 8.5 (0.95) | 7.54 (0.87 | − 1 (0.85) | < 0.001 |
Gla-100 OD + MET followed by lispro mix 75/25 BD | 8.48 (0.8) | 8.14 (1.03 | − 0.42 (0.92) |
Author, year | Mean FPG (SD if available) | Mean change (SD if available) | Intergroup p value | PPG (SD if available) | Mean change (SD if available) | Intergroup p value | ||
---|---|---|---|---|---|---|---|---|
Baseline | Post treatment | Baseline | Baseline | |||||
Gla-100 vs. NPH insulin | ||||||||
Fiesselmann, 2016 [14] | – | – | 43.6 (57.4) | < 0.01 | – | – | – | – |
– | – | 30.3 (46.9) | – | – | – | |||
Home PD, 2014 [15] | 165.6 (37.8) | 111.6 (21.6) | 51.3 (1.08) | 0.009 | – | – | – | – |
160.2 (34.2) | 115.2 (21.6) | 48.24 (1.08) | – | – | – | |||
Delgado E, 2012 [16] | 179.2 | 137.8 | – | < 0.0001 | – | – | – | – |
161.6 | 157.3 | – | – | – | – | |||
Mu P, 2011 [18] | 183.78 (50.76) | 99 (3.96) | – | – | 291.6 (77.94) | 138.78 (9.36) | – | < 0.05 |
189.36 (11.34) | 97.56 (4.68) | – | 284.4 (71.46) | 148.78 (11.34) | – | |||
Hsia SH, 2011 [17] | 147 (40) | 113 (19) | − 33 (39) | – | – | – | – | – |
171 (48) | 125 (27) | − 46 (45) | – | – | – | |||
Mattia, 2009 [19] | 203.6 (58.3) | 103.7 | 99.9 | – | – | – | – | – |
203.6 (58.3) | 103.2 | 100.4 | – | – | – | |||
Pan, 2007 [20] | 226 (51) | 117 (25) | − 106 | – | – | – | – | – |
223 (53) | 119 (26) | − 104 | – | – | – | |||
Eliaschewitz, 2006 [22] | 201.8 (58.7) | 115.6 (36) | − 86.2 (67.2) | – | – | – | – | – |
194.1 (56.6) | 19.5 (44.1) | − 74.6 (66.2) | – | – | – | |||
Jarvinen, 2006 [21] | 203.4 (1.8) | 102.6 (0.36) | – | – | – | – | – | – |
198 (1.8) | 108 (0.54) | – | – | – | – | – | – | |
Shi, 2004 [23] | 146.5 (38.2) | 122.4 (39.6) | – | – | – | – | – | – |
163.9 (39.1) | 160.2 (63) | – | – | – | – | |||
Riddle, 2003 [25] | 198 (11) | 117 | − 81 | – | – | – | – | – |
194 (10.8) | 120 | − 74 | – | – | – | |||
Benedetti, 2003 [24] | 178.2 (3.6) | – | − 48.6 (1.8) | < 0.05 | – | – | – | – |
180 (3.6) | – | 46.8 (1.8) | – | – | – | |||
Yki-Jarvinen, 2000 [26] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | |||
Gla-100 vs. premixed insulin | ||||||||
Petrovski, 2018 [27] | 217.8 (66.6) | 138.6 (37.8) | – | < 0.05 | – | – | – | – |
Cao Y, 2017 [29] | 163.98 (43.74) | – | – | – | – | – | – | – |
182.16 (38.34) | – | – | – | – | – | |||
Zhang, 2017 [28] | 145.8 (37.8) | 120.6 (32.4) | 25.2 (43.2) | < 0.0001 | 207 (61.2) | 171 (45) | 37.8 (70.2) | < 0.0001 |
Sehgal S, 2015 [7] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | – | ||
– | – | – | – | – | – | – | ||
Sun, 2014 [11] | 200.16 (28.08) | 165.24 (16.56) | – | – | 353.26 (94.14) | 162.18 (38.52) | – | – |
201.6 (25.02) | 170.10 (17.1) | – | 363.78 (110.34) | 181.8 (30.78) | – | |||
Zhang Y, 2014 [12] | 137.52 (24.48) | 100.26 (21.78) | – | < 0.01 | 217.26 (21.06) | 160.96 (28.08) | – | < 0.01 |
Sakharova O V 2013 [30] | 188 (64) | 108 (36) | – | – | 294 (97) | 153 (36) | – | 0.001 |
188 (64) | 110 (22) | – | 294 (97) | 199 (49) | – | |||
Kalra, 2010 [31] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | |||
Buse, 2009 [33] | 193 (53.2) | 134 (35) | – | < 0.0001 | – | – | – | – |
196 (55.1) | 122 (33) | – | – | – | – | |||
Strojek, 2009 [32] | – | – | – | – | – | – | – | – |
– | – | – | - | - | - | |||
158 (35) | 122 ± 34 | – | – | – | – | – | – | |
171 (61) | 128 ± 31 | - | - | - | - | - | - | |
153 (49) | 133 (43.0) | – | – | – | – | |||
Robbins, 2007 [35] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | |||
Raskin, 2007 [36] | 255.6 (70.02) | 128.88 (75.06) | – | – | – | – | – | – |
239.4 (74.16) | 126 (61.2) | – | – | – | – | – | ||
Jacober, 2006 [37] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | |||
Kazda, 2006 [10] | 176.4 (50.4) | – | 16.2 (39.6) | < 0.001 | 205.2 (61.2) | 151.2 | − 54 (63) | – |
167.4(37.8) | – | 16.2 (32.4) | 214.2 (50.4) | 163.8 | − 50.4 (52.2) | |||
172.8 (43.2) | – | 46.08 (43.2) | 219.6 (55.8) | 172.8 | − 46.8 (59.4) | |||
Bullano, 2006 [38] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | |||
Roach, 2006 [13] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | |||
Janka, 2005 [39] | 171 (35) | 115 | – | < 0.0001 | – | – | – | – |
172 (38) | 133 | – | – | – | – | |||
Raskin, 2005 [40] | 252 (67.4) | 127 (40.6) | 125 (72.9) | – | – | – | – | – |
243 (68.8) | 117 (44.3) | 125 (74.) | – | – | – | |||
Malone, 2004 [41] | 150.2 (44.7) | 139.3 (36.6) | 11.3 (44.5) | 0.001 | – | – | – | - |
155.3 (50.1) | 123.9 (34.9) | 29 (47.4) | – | – | – | |||
Gla-100 vs. second-generation basal insulin | ||||||||
Bailey, 2019 [42] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | |||
Gupta, 2018 [43] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | |||
– | – | – | - | - | - | |||
Nakanishi, 2018 [6] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | – | ||
Wysham, 2017 [45] | 134.9 (51.6) | 107.6 (51.3) | – | – | – | – | – | – |
139.2 (53.5) | 114.1 (51.9) | – | – | – | – | |||
Marso, 2017 [44] | 169.8 (70.3) | 128 (56) | 39.9 | < 0.0001 | – | – | – | – |
173.5 (70.7) | 136 (57) | 34.9 | – | – | – | |||
Pan, 2016 [46] | 169.2 (43.2) | 108 (36) | 60.30 (52.38) | – | – | – | – | – |
169.2 (45) | 113.4 (34.2) | 56.52 (48.78) | – | – | – | |||
Ghosal, 2016 [47] | 182.88 (37.25) | 107 (19.25) | 75.88 (40.15) | – | – | – | – | – |
182.35 (34.85) | 109.55 (24.20) | 72.81 (37.71) | – | – | – | |||
Terauchi, 2016 [8] | 138.6 (37.8) | - | 21.8 (2.9) | – | – | – | – | – |
133.2 (34.2) | - | 22.5 (2.9) | – | – | – | |||
Bolli, 2015 [48] | 178.74 (51.48) | 120 (38.88) | 61.2 (1.8) | – | – | – | – | – |
183.6 (52.2) | 113.4 (32.76) | 68.4 (1.98) | – | – | – | |||
Yki-J¨arvinen, 2014 [49] | 8.24 (2.97) | 7.09 (2.47) | 1.14 (3.42) | – | – | – | – | – |
7.89 (2.67) | 6.83 (2.37) | 1.06 (3.02) | – | – | – | |||
Gough SC, 2013 [50] | 172.4 (51.7) | 105.7 | 66.7 | – | – | – | – | – |
174.1 (46.8) | 113.1 | 60.9 | – | – | – | |||
Onishi Y 2013 [51] | 151.2 (37.8) | 99 | 51.84 | – | – | – | – | – |
154.8 (34.2) | 102.6 | 53.46 | – | – | – | |||
Meneghini L 2013 [52] | 162 (46.8) | 104.4 | - | 0.04 | – | – | – | – |
158.4 (50.4) | 104.4 | - | – | – | – | |||
162 (50.4) | 111.6 | - | – | – | – | |||
Zinman B, 2012 [53] | 172.8 (46.8) | 106.2 | 68.4 (54.72) | – | – | – | – | – |
174.6 (46.8) | 115.2 | 59.4 (51.66) | – | – | – | |||
Gla-100 vs. Co-formulations | ||||||||
Kumar, 2017 [54] | 144 (45) | 113.4 | – | – | – | – | – | – |
140 (50) | 108 | – | – | – | – | – | ||
Kumar, 2016 [55] | 187.4 (50.5) | - | 67.86 | – | – | – | – | – |
182 (52.3) | - | 63 | – | – | – | |||
Onishi Y 2013 [56] | 162 (28.8) | 102.6 (37.8) | 59.4 (43.2) | – | – | – | – | – |
163.8 (34.2) | 100.8 (34.2) | 63 (43.2) | – | – | – | |||
Gla-100 vs. other basal insulins | ||||||||
Cander S, 2014 [57] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | |||
– | – | – | – | – | – | |||
Odawara M, 2014 [58] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | |||
Wei W, 2014 [59] | – | – | – | – | – | – | – | – |
– | – | – | – | – | – | |||
– | – | – | – | – | – | |||
– | – | – | – | – | – | |||
– | – | – | – | – | – | |||
– | – | – | – | – | – | |||
Meneghini L, 2013 [60] | 156 (40.7) | 112 (33.8) | − 44.8 (46.3) | – | – | – | – | – |
152.4 (39.8) | 109.6 (42.8) | − 43.4 (52.7) | – | – | – | |||
Esposito, 2008 [61] | 192 (41) | 107 (11) | – | – | – | – | – | – |
193 (40) | 105 (12) | – | – | – | – | |||
Rosenstock, 2008 [9] | 194.4 | 128.52 (3.78) | – | – | – | – | – | – |
194.4 | 125.64 (3.78) | – | – | – | – | |||
Malone, 2005 [62] | 155.34 (52.74) | 142.2 (34.56) | – | < 0.007 | – | – | – | – |
147.78 (37.62) | 133.02 (35.28) | – | – | – | – |
Intensification
Author, year | Intervention | Study duration (months) | Mean HbA1c (SD if available) | Mean change (SD if available) | Intergroup p value | Mean FPG (SD if available) | Mean change (SD if available) | Intergroup p value | ||
---|---|---|---|---|---|---|---|---|---|---|
Baseline | Post-treatment | Baseline | Post-treatment | |||||||
Gla-100 vs. NPH insulin | ||||||||||
Betonico, 2019 [72] | Gla-100 OD + insulin lispro TID for 24 weeks followed by insulin NPH + lispro TID | 9–12 | 8.9 (1.3) | 7.95 (1.1) | – | 0.028 | – | – | – | – |
Insulin NPH + insulin lispro TID for 24 weeks followed by Gla-100 OD + lispro TID | 8.6 (1.1) | 8.44 (1.3) | – | – | – | – | ||||
Rosenstock, 2001 [73] | Gla-100 OD ± premeal regular insulin | 6–9 | 8.6 (1.2) | – | – | – | – | – | – | – |
NPH insulin OD / BD ± premeal regular insulin | 8.5 (1.2) | – | – | – | – | – | ||||
Gla-100 vs. premixed insulins | ||||||||||
Aschner, 2015 [74] | Gla-100 OD + glulisine OD before main meal + MET ± SU | 6–9 | 8.7 (0.9) | 7.2 (0.9) | − 1.48 (0.04) | 0.0008 | 160.2 (37.8) | 108 (21.6) | -54 (1.08) | < 0.001 |
Premixed insulin BD MET ± SU | 8.7 (0.9) | 7 (0.9) | − 1.64 (0.04) | 162 (41.4) | 113.4 (25.2) | - 46.8 (1.08) | ||||
Tentolouris N, 2013 [83] | Premixed BD continued | > 12 | 8.18 (1.33) | 7.58 (1.06) | − 0.6 | < 0.001 | 168.9 (47.2) | 148.5 (42.7) | - 19.73 | < 0.001 |
Premixed BD switched to Gla-100 OD + rapid-acting insulin | 8.53 (1.29) | 7.39 (0.81) | − 1.14 | 182.6 (57.1) | 135.6 (34.5) | - 47.02 | ||||
Ito H, 2014 [71] | Human premixed insulin 50/50 switched to Gla-100 OD + glulisine BD | 3–6 | 8.3 (1.8) | 8.2 (1.1) | − 0.1 (1.4) | NS | – | – | – | – |
Tinahones, 2014 [75] | Insulin lispro Mix BD + MET ± pioglitazone | 6–9 | 8.7 (0.8) | Not mentioned | − 1.3 | 0.010 | – | – | – | – |
Gla-100 OD + insulin lispro OD + MET ± pioglitazone | 8.6 (0.7) | Not mentioned | − 1.08 | – | – | – | – | |||
Jain, 2010 [67] | Gla-100 OD + mealtime lispro TID | 6–9 | 9.3 (1.2) | 7.50 (0.20) | − 1.8 | NS | – | – | – | – |
Insulin lispro mix 50/50 TID | 9.5 (1.2) | 7.58 (0.20) | − 1.92 | - | - | - | ||||
Rosenstock, 2008 [76] | Prandial premixed (insulin lispro protamine suspension/lispro) | 6–9 | 8.83 (1.04) | 6.95 | − 1.87 | 0.021 | – | – | – | – |
Gla-100 OD + insulin lispro TID + OADs (minus SU + glinides) | 8.89 (1.09) | 6.78 | − 2.09 | – | – | – | ||||
Joshi, 2005 [70] | Premixed insulin analog (NovoMix 30) BD | 3–6 | 8.79 (1.13) | 7.2 (0.83) | − 1.59 | < 0.05 | 186.59 (47.35) | 114.83 (18.68) | Not mentioned | NS |
Gla-100 OD + insulin aspart TID | 8.53 (1.22) | 7.37 (0.83) | − 1.16 | 190.23 (55.63) | 110.61 (16.79) | Not mentioned | ||||
Fritsche, 2010 [64] | Once-daily insulin glargine bedtime every day and insulin glulisine 0–15 min before mealtime | > 12 | 8.6 (0.8) | 7.3 (1.2) | − 1.3 (1.2) | 0.0001 | 177 (54) | 134 (57) | - 43 (70) | 0.0684 |
Twice-daily premixed insulin (pre-breakfast and evening meal) | 8.5 (0.9) | 7.7 (1.1) | − 0.8 (1.0) | 174 (59) | 144 (52) | - 29 (59) | ||||
Levin, 2011 [77] | Insulin glargine/glulisine therapy | 6–9 | 9.33 (1.8) | 6.93 | − 2.3 | < 0.01 | – | – | – | – |
Premixed analogue therapy | 9.35 (1.8) | 7.52 | − 1.7 | – | – | – | ||||
Bowering, 2012 [78] | Premixed TID stepwise (lispro mix 75:25) + metformin ± sulfonylurea)) | 9–12 | 8.98 (1.04) | 7.1 (1.04) | − 1.84 | NS | – | – | – | – |
Gla-100 OD + insulin lispro TID (stepwise fashion) + metformin | 9.03 (1.05) | 7.3 (1.03) | − 1.8 | = | - | - | ||||
Miser, 2010 [63] | Intensification arm – A: Premixed TID (lispro mix 75:25) + OADs (minus sulfonylurea)) | 6–9 | 8.0 (1) | 8.0 (1.2) | – | NS | – | – | – | – |
Intensification arm – A: Gla-100 OD + insulin lispro TID + OADs (minus sulfonylureas) | 8.0 (1) | 8.1 (1.5) | – | – | – | – | ||||
Intensification arm – B: Premixed TID (lispro mix 50:50) + OADs (minus sulfonylurea)) | 8.0 (0.9) | 8.2 (1.3) | – | – | – | – | ||||
Intensification arm – B: Gla-100 OD + insulin lispro TID + OADs (minus sulfonylureas) | 8.0 (0.9) | 8.2 (1.4) | – | – | – | – | ||||
Riddle, 2014 [66] | G + 1 | > 12 | 9.4 (1.7) | 7.1 (1.68) | − 2.3 (0.12) | 0.05 vs. premix | 198 (70.2) | 117 (57.6) | - 79.2 (73.2) | 0.0005 vs. premix |
G + 3 | 9.4 (1.7) | 7.0 (1.21) | − 2.4 (0.12) | 0.005 vs. premix | 207 (75.6) | 115.2 (48.6) | - 86.4 (90) | 0.0002 vs. premix | ||
PM (2 +) | 9.3 (1.6) | 7.2 (1.37) | − 2.0 (0.12) | 203.4 (64.8) | 133.2 (55.8) | - 61.2 (72) | ||||
Vora, 2015 [65] | Gla-100 OD + insulin glulisine OD + metformin | 6–9 | 8.6 (0.9) | - | − 1.0 | NS | 109.8 (28.8) | – | – | – |
Premixed BD (insulin aspart 70/30 BID) + metformin | 8.6 (0.9) | - | − 1.22 | 108 (28.8) | – | – | – | |||
Jia, 2015 [79] | Gla-100 OD + insulin lispro TID + OADs | 6–9 | 8.7 (1.1) | – | − 1.1 | NS | – | – | – | – |
Premixed TID (lispro 50/50 BID + lispro 75/25 OD + OADs | 8.6 (1) | – | − 1.1 | – | – | – | – | |||
Giugliano, 2014 [68] | Gla-100 OD + insulin lispro TID (stepwise fashion) + OADs | 9–12 | 9.07 (0.99) | 7.58 | − 1.57 (0.10) | NS | – | – | – | – |
Premixed TID (lispro 75/25 or lispro 50/50) stepwise + OADs | 8.98 (0.95) | 7.40 | − 1.65 (0.10) | – | – | – | – | |||
Gla-100 vs. second-generation basal insulins | ||||||||||
Riddle, 2014 [81] | Gla-300 OD + meal-time insulin ± MET | 6–9 | 8.15 (0.78) | 7.25 (0.85) | – 0.83 (0.06) | – | 158.3 (51.8) | 130.32 (46.26) | – | – |
Gla-100 OD + meal-time insulin ± MET | 8.16 (0.77) | 7.28 (0.92) | – 0.83 (0.06) | 160.7 (52.8) | 129.78 (43.2) | – | ||||
Hollander, 2015 [80] | IDeg OD | > 12 | 8.2 (0.8) | 7.2 | − 1 | – | 165.6 (54) | – | − 43.2 | – |
Gla-100 OD | 8.3 (0.9) | 7.1 | − 1.2 | 165.6 (57.6) | – | − 39.6 | ||||
Gla-100 vs. co-formulations | ||||||||||
Philis-Tsimikas A, 2019 [82] | IDegAsp OD / BD ± OADs minus SU & glinide | 9–12 | 8.2 (0.8) | – | − 1.3 (0.8) | – | 162 (48) | – | − 48.6 (54) | – |
Gla-100 OD + aspart ± OADs minus SU & glinides | 8.1 (0.7) | – | − 1.2 (0.8) | 158 (48) | – | − 41.4 (55.8) | ||||
Gla-100 vs. other basal insulins | ||||||||||
Raskin, 2009 [84] | IDet OD + aspart ± MET ± TZDs | 6–9 | 8.4 (1) | 7.13 (0.013) | − 1.08 (1.077) | 0.035 | 174 (3.73) | 129.7 (3.16) | − 43.2 (3.16) | – |
Gla-100 OD + aspart ± MET ± TZDs | 8.4 (1) | 6.92 (0.091) | − 1.28 (1.117) | 172.2 (5.11) | 134.3 (4.32) | − 38.7 (4.32) | ||||
Hollander, 2008 [85] | IDet OD + aspart + OADs (minus secretagogues and α-glucosidase inhibitors) | > 12 | 8.6 (1) | 7.19 | − 1.52 | NS | 171 (54) | 127 | − 46.08 | NS |
Gla-100 OD + aspart + OADs (minus secretagogues and α-glucosidase inhibitors) | 8.8 (1.1) | 7.03 | − 1.68 | 176.4 (52.2) | 120.2 | − 52.56 |
Clinical Outcomes
Insulin Initiation
Gla-100 vs. NPH Insulin
Gla-100 vs. Premixed Insulins
Gla-100 vs. Second-Generation Basal Insulins
Gla-100 vs. Co-formulations
Gla-100 vs. Other First-Generation Basal Insulins
Other Outcomes
Author, year | Study duration (months) | Overall hypoglycemiaa | Intergroup p value | Nocturnal hypoglycemiaa | Intergroup p value | Severe hypoglycemiaa | Intergroup p value |
---|---|---|---|---|---|---|---|
Gla-100 vs. NPH insulin | |||||||
Fiesselmann, 2016 [14] | 6–9 | 7.4 vs. 19.3 | – | 1.4 vs. 10.5 | – | 0.4 vs. 2.1 | – |
Home PD, 2014 [15] | 9–12 | 64.7 vs. 61.1 | – | 34.7 vs. 38 | – | – | – |
Delgado E, 2012 [16] | 3–12 | 21.8 vs. 47.6 | < 0.0001 | 1.3 vs. 8.3 | – | 0.2 vs. 1.85 | – |
Mu P, 2011 [18] | 3–6 | 4.84 vs. 7.14 | – | – | – | 0 vs. 0 | – |
Hsia SH, 2011a [17] | 6–9 | 96 vs. 77 vs. 77 | – | 20 vs. 13 vs. 10 | |||
Mattia, 2009 [19] | 3–6 | 1.04 vs. 2.12 episodes/patient/month | – | 0 vs. 0 | – | – | – |
Pan, 2007 [20] | 6–9 | 682 vs. 1019 | < 0.004 | 5 vs. 28 | < 0.03 | 221 vs. 620 | < 0.001 |
Jarvinen, 2006 [21] | 9–12 | 5.4 vs. 8 | – | 98% vs. 93% of the confirmed symptomatic hypoglycemia | NS | – | – |
Eliaschewitz, 2006 [22] | 6–9 | 52.8 vs. 62.8 | < 0.042 | 20.4 vs. 34.8 | < 0.001 | 2.6 vs. 4.4 | 0.303 |
Shi, 2004 [23] | 6–9 (24) | 7.1 vs. 35.7 | 0.008 | – | – | - | – |
Riddle, 2003 [25] | 6–9 | 13.9 vs. 17.7 | < 0.02 | 4 vs. 6.9 | < 0.001 | 2.5 vs. 1.9 | – |
Benedetti, 2003 [24] | > 12 | 35 vs. 41 | – | 12 vs. 24 | 0.0002 | – | – |
Yki-Jarvinen, 2000 [26] | > 12 | 33 vs. 42 | < 0.04 | 9.9 vs. 24 | < 0.001 | – | – |
Gla-100 vs. premixed insulin | |||||||
Petrovski, 2018 [27] | 6–9 | 5.2% | – | 0.8% | – | 0 | – |
Cao Y, 2017 [29] | 3–6 | 2.85 vs. 13.3 | < 0.01 | – | – | – | – |
Zhang, 2017 [28] | 3–6 | 15.5 | – | 1.1% | - | 0.3% | – |
Sehgal S, 2015 [7] | > 12 | – | – | – | – | 4.0 vs. 0.0 vs. 11.9 | – |
Sun, 2014 [11] | 6–9 | 10.6 vs. 13.8% | NS | – | – | – | – |
Zhang Y, 2014 [12] | 3–6 | 0.3 episodes /patient/month | - | – | – | – | – |
Sakharova O V 2013 [30] | 3–6 | – | – | – | – | 0 vs. 0 | – |
Kalra, 2010 [31] | 6–9 | 4.5 vs. 6.2 episodes/patient/year | – | 0.9 vs.0.9 episodes/patient/year | – | – | – |
Buse, 2009 [33] | 6–9 | 23.1 vs. 28 episodes/patient/year | 0.007 | 11.4 vs. 8.9 episodes/patient/year | 0.009 | 0.03 vs. 0.10 episodes/patient/year | – |
Strojek, 2009 [32] | 6–9 | 4.8 vs. 6.5 episodes/patient/year | 0.034 | 0.5 vs. 1.1 episodes/patient/year | 0.003 | - | – |
Schiel, 2007 [34] | 3–6 | 59 or 72 vs. 77 | – | – | – | – | – |
Robbins, 2007 [35] | 6–9 | 0.5 vs. 0.8 episodes/patient/month | – | 0.3 vs. 0.2 episodes/patient/month | – | – | – |
Raskin, 2007 [36] | 6–9 | 42 vs. 68 | 0.0013 | 10 vs. 25 | 0.021 | 0 vs. 0 | – |
Jacober, 2006 [37] | 6–9 | 2.57 vs. 3.98 episodes/patient/month | 0.0013 | 1.05 vs. 0.80 episodes/patient/month | NS | 0 vs. 0 | - |
Kazda, 2006 [10] | 6–9 | 1 vs. 1.5 or 1.4 episode/100 patient-years | – | – | – | – | – |
Bullano, 2006 [38] | - | 19.1 vs. 16.5 events /100-patients/year | – | – | – | – | – |
Roach, 2006 [13] | 6–9 | 30 vs. 80 | – | – | – | – | – |
Janka, 2005 [39] | 6–9 | 4.07 vs. 9.87 events per patient-years | < 0.0001 | 0.51 vs. 1.04 events per patient-years | 0.0449 | 0 vs. 0.05 | - |
Raskin, 2005 [40] | 6–9 | 0.7 vs. 3.4 episodes/patient/year | < 0.05 | – | – | 1 vs. 0 | – |
Malone, 2004 [41] | 9–12 | 0.39 vs. 0.68 episodes/patient/month | 0.04 | 0.14 vs. 0.24 episodes/patient/month | – | – | – |
Gla-100 vs. second-generation basal insulins | |||||||
Bailey, 2019 [42] | 6–9 | 9.66 vs. 12.45 | – | – | – | – | – |
Gupta, 2018 [43] | 6–9 | 0.08 vs. 0.04 vs. 0.13 events / PYE | 0.018 | - | - | - | – |
Nakanishi, 2018 [6] | 3–6 | – | – | – | – | – | – |
Marso, 2017 [44] | > 12 | – | – | – | – | 3.70 vs. 6.25 episodes / 100 PYE | < 0.001 |
Wysham, 2017 [45] | > 12 | 275.1 vs. 219.9 episodes/ 100 PYE | < 0.001 | 88.4 vs. 72 episodes/100 PYE | < 0.001 | 9.4 vs. 4.4 episodes / 100 PYE | 0.03 |
Ghosal, 2016 [47] | 6–9 | 19.4 vs. 64.6 | – | - | – | - | – |
Pan, 2016 [46] | 6–9 | 85 vs. 97 episodes/100PYE | – | 22 vs. 24 episodes/100 PYE | – | 2 vs. 1 episode/100 PYE | – |
Terauchi, 2016 [8] | 6–9 | 11.55 vs. 17.87 episodes / PYE | – | 2.44 vs. 5.3 episodes / PYE | – | 0.05 vs. 0.03 episodes / PYE | – |
Bolli, 2015 [48] | 6–9 | 6.4 vs. 8.5 events/PYE | 0.042 | 16 vs. 17 | NS | 1 vs. 1 episode | – |
Yki-Jarvinen, 2014 [49] | 6–9 | 14.37 vs. 18.96 episodes / PYE | – | 1.98 vs. 3.95 episodes / PYE | Not mentioned | 0.03 vs. 0.06 episodes / PYE | – |
Gough SC, 2013 [50] | 6–9 | 1.22 vs. 1.42 episodes/PYE | – | 0.18 vs. 0.28 episodes/PYE | – | – | – |
Meneghini L 2013 [52] | 6–9 | 3.6 vs. 3.6 vs. 3.5 episodes/ PYE | – | 0.6 vs. 0.6 vs. 0.8 episodes/PYE | – | – | – |
Onishi Y 2013 [51] | 6–9 | 3.0 vs. 3.7 episodes/PYE | – | 0.8 vs. 1.2 episodes/PYE | – | – | – |
Zinman B, 2012 [53] | > 12 | 1.52 vs. 1.85 episodes / patient/ year | – | 0.25 vs. 0.39 episodes/patient/year | 0.038 | 0.003 vs. 0.023 episodes/patient/year | 0.017 |
Gla-100 vs. co- formulations | |||||||
Kumar, 2017 [54] | 6–9 | 52.6 vs. 48.1% of the patients | < 0.05 | 19.1 vs. 21.0% of the patients | – | – | – |
Kumar, 2016 [55] | > 12 | Treatment ratio is 1.86 in favor of Gla-100 | < 0.0001 | Treatment ratio is 10.25 in favor of IDegAsp | < 0.0001 | 0.01 vs. 0.01 events / PYE | - |
Onishi Y 2013 [56] | 6–9 | 1.91 vs. 2.71 episodes/ PYE | – | 0.39 vs. 0.53 episodes/PYE | – | – | – |
Gla-100 vs. other basal insulins | |||||||
Cander S, 2014 [57] | 3–6 | 0.0 vs. 0.5 vs. 0.0 episodes/patient/week | – | – | – | – | – |
Wei W, 2014 [59] | 3–6 | 0.30 vs. 0.37 vs. 0.37 vs. 0.41 vs. 0.26 vs. 0.21 episodes /PYE | – | – | – | – | – |
Meneghini L, 2013 [60] | 6–9 | 3.19 vs. 4.41 episodes / PYE | 0.034 | 1.11 vs. 0.88episodes /PYE | – | – | – |
Esposito, 2008 [61] | 9–12 | 7.5 vs. 6.0 episodes/PYE | – | 33 vs. 25 | – | – | – |
Rosenstock, 2008 [9] | > 12 | 5.8 vs. 6.2 episodes/patient-year | – | 1.3 vs. 1.3 episodes/patient-year | – | 0 | – |
Malone, 2005 [62] | 9–12 | 0.61 vs. 0.44 episodes / patient / 30 days | – | 0.14 vs. 0.34 episodes / patient / 30 months | 0.002 | – | – |
Author, year | Weight change from baseline; mean | Intergroup p value | Baseline Insulin dose | Post-treatment insulin dose | Intergroup p value |
---|---|---|---|---|---|
Gla-100 vs. NPH insulin | |||||
Fiesselmann, 2016 [14] | 0.8 vs. 0.1 | < 0.05 in favor of NPH | – | – | – |
Home PD, 2014 [15] | 1.26 vs. 1.05 | – | 0.2 vs. 0.2 U/kg/day | 0.39 vs. 0.36 U/kg/day | – |
Delgado E, 2012 [16] | – | – | 34 vs. 34 | 30 vs. 36 | – |
Mu P, 2011 [18] | – | – | – | – | – |
Hsia SH, 2011a [17] | -0.2 vs. 1.7 vs. 3.1 | 0.01 in favor of NPH | – | 14.6 vs. 17.7 vs. 17.9 U/day | – |
Mattia, 2009 [19] | - | - | 10 vs. 10 U/day | 28.8 vs. 34.7 U/day | – |
Pan, 2007 [20] | - | - | 9.6 vs. 9.6 U/day | 32.1 vs. 32.1 U/day | – |
Jarvinen, 2006 [21] | 2.6 vs. 3.5 | – | – | 68 vs. 70 | – |
Eliaschewitz, 2006 [22] | – | – | 16.2 vs. 14.9 U/day | 32.6 vs. 31.2 U/day | – |
Shi, 2004 [23] | – | – | – | – | – |
Riddle, 2003 [25] | 3.0 vs. 2.8 | – | 10 vs. 10 U/day | 47.2 vs. 41.8 U/day | < 0.005 in favor of Gla-100 |
Benedetti, 2003 [24] | 2.01 vs. 1.88 | – | – | - | – |
Yki-Jarvinen, 2000 [26] | 2.57 vs. 2.34 | – | – | 23 vs. 21 U/day | – |
Gla-100 vs. premixed insulin | |||||
Petrovski, 2018 [27] | - | < 0.001 in favor of Gla-100 | - | - | - |
Cao Y, 2017 [29] | -0.33 vs. 1.65 | < 0.05 in favor of Gla-100 | - | 21 vs. 58 U/day | - |
Zhang, 2017 [28] | -0.2 | < 0.0001 in favor of Gla-100 | 29.4 U/day | 16.0 U/day | - |
Sehgal S, 2015 [7] | 1.9 vs. 1.1 vs. 0.9 | - | 0.2 vs. 0.2 vs. 0.3 U/kg/day | 0.3 vs. 0.3 vs. 0.5 U/kg/day | NS |
Sun, 2014 [11] | - | - | 0.2 vs. 1.0 U/kg/day | - | - |
Zhang Y, 2014 [12] | - | - | 30.2 U/day | 16.38 U/day | - |
Sakharova O V 2013 [30] | 2.4 vs. 1.7 | - | - | 0.4 vs. 0.3 U/kg/day | - |
Kalra, 2010 [31] | 0.8 vs. 1.16 | - | 0.2 vs. 0.2 U/kg/day | 0.4 vs. 0.35 U/kg/day | NS |
Buse, 2009 [33] | 3.6 vs. 2.5 | < 0.0001 in favor of Gla-100 | - | 0.47 vs. 0.40 U/kg/day | < 0.001 in favor of Gla-100 |
Strojek, 2009 [32] | 1.74 vs. 1.67 | - | 0.2 vs. 0.2 U/kg/day | 0.29 vs. 0.32 U/kg/day | NS |
Schiel, 2007 [34] | 0.77 vs. - 0.31 vs. 0.21 | - | 77.6 vs. 64.9 vs. 65.2 U/day | 75.1 vs. 53.9 vs. 70.6 U/day | NS |
Robbins, 2007 [35] | - 0.5 vs. 1.2 | < 0.001 | 0.6 vs. 0.6 U/kg/day | 0.6 vs. 0.7 U/kg/day | < 0.001 in favor of Gla-100 |
Raskin, 2007 [36] | 5.4 vs. 3.0 | 0.0004 in favor of Gla-100 | 0.14 vs. 0.14 | 0.91 vs. 0.57 | - |
Jacober, 2006 [37] | - | - | - | 0.25 vs. 0.27 U/kg/day | - |
Kazda, 2006 [10] | 2.3 vs. 1.8 vs. 0.7 | - | 0.25 vs. 0.30 vs. 0.16 U/kg/day | 0.50 vs. 0.59 vs. 0.43 U/kg/day | < 0.005 in favor of Gla-100 |
Bullano, 2006 [38] | – | – | – | – | – |
Roach, 2006 [13] | – | – | – | 44 vs. 60 U/day | – |
Janka, 2005 [39] | 1.4 vs. 2.1 | - | 9.9 vs. 20.6 | 28.2 vs. 64.5 | < 0.05 in favor of Gla-100 |
Raskin, 2005 [40] | 5.4 vs. 3.5 | < 0.01 in favor of Gla-100 | 0.14 vs. 0.13 | 0.82 vs. 0.55 | < 0.05 in favor of Gla-100 |
Malone, 2004 [41] | 2.3 vs. 1.6 | 0.006 in favor of Gla-100 | 0.39 vs. 0.39 | 0.62 vs. 0.57 | < 0.001 in favor of Gla-100 |
Gla-100 vs. second-generation basal insulins | |||||
Bailey, 2019 [42] | – | – | – | – | – |
Gupta, 2018 [43] | – | – | 0.339 vs. 0.331 vs. 0.73 U/kg/day | 0.44 vs. 0.43 vs. 0.58 U/kg/day | – |
Nakanishi, 2018 [6] | – | – | 8.7 vs. 11.1 U/day | 8.6 vs. 10.8 U/day | – |
Marso, 2017 [44] | 4.9 vs. 4.9 | – | – | – | 0.04 in favor of Gla-100 |
Wysham, 2017 [45] | 0.9 vs. 0.5 | – | 43.0 vs. 40.0 U/day | 83.0 vs. 83.0 U/day | – |
Ghosal, 2016 [47] | 0.85 vs. 1.65 | – | – | 18.61 vs. 25.68 U/day | 0.002 in favor of IDeg |
Pan, 2016 [46] | 2.2 vs. 1.8 | – | 0.14 vs. 0.14 U/kg/day | 0.49 vs. 0.50 U/kg/day | – |
Terauchi, 2016 [8] | 0.4 vs. 0.6 | 0.0003 in favor of Gla-100 | 0.23 vs. 0.24 U/kg/day | 0.35 vs. 0.30 U/kg/day | – |
Bolli, 2015 [48] | 0.71 vs. 0.49 | - | 0.2 vs. 0.2 U/kg/day | 0.62 vs, 0.53 U/kg/day | – |
Yki-Jarvinen, 2014 [49] | 0.66 vs. 0.08 | 0.015 in favor of Gla-300 | 0.64 vs. 0.66 U/kg/day | 0.92 vs. 0.84 U/kg/day | < 0.05 in favor of Gla-100 |
Gough SC, 2013 [50] | 1.9 vs. 1.5 | – | 11.0 vs. 10.0 U/day | 0.53 vs. 0.60 U/kg/day | < 0.05 in favor of IDeg |
Meneghini L 2013 [52] | 1.5 vs. 1.6 vs. 1.3 | – | 0.2 vs. 0.2 vs. 0.2 U/kg/day | 0.6 vs. 0.6 vs. 0.6 U/kg/day | – |
Onishi Y 2013 [51] | 1.3 vs. 1.4 | – | 0.14 vs. 0.14 U/kg/day | 0.28 vs. 0.35 U/kg/day | 0.0004 in favor of IDeg |
Zinman B, 2012 [53] | 2.4 vs. 2.1 | – | 0.12 vs. 0.11 U/kg/day | 0.59 vs. 0.60 U/kg/day | - |
Gla-100 vs. co-formulations | |||||
Kumar, 2017 [54] | 1.74 vs. 1.41 | – | – | 0.69 vs. 0.69 U/kg/day | – |
Kumar, 2016 [55] | 2.8 vs. 4.4 | < 0.0001 in favor of Gla-100 | – | 0.70 vs. 0.78 U/kg/day | – |
Onishi Y 2013 [56] | 0.7 vs. 0.7 | - | 11.0 vs. 10.0 U/day | 29.0 vs. 28.0 U/day | – |
Gla-100 vs. other basal insulins | |||||
Cander S, 2014 [57] | 1.0 vs. 0.0 vs. 1.1 | – | 0.12 vs. 0.12 vs. 0.12 U/kg/day | 0.25 vs. 0.22 vs. 0.19 U/kg/day | – |
Wei W, 2014 [59] | – | – | 46.6 vs. 45.1 vs. 41.1 vs. 40.0 vs. 49.3 vs. 51.2 U/day | 47.6 vs. 48.4 vs. 41.5 vs. 42.1 vs. 54.6 vs. 53.0 U/day | – |
Meneghini L, 2013 [60] | 0.49 vs. 1.0 | < 0.05 in favor of IDet | 0.2 vs. 0.2 U/kg/day | 0.70 vs. 0.61 U/kg/day | 0.0119 in favor of Gla-100 |
Esposito, 2008 [61] | 2.4 vs. 2.8 | - | 11.0 vs. 10.0 U/day | 52.0 vs. 57.0 U/day | - |
Rosenstock, 2008 [9] | 2.8 vs. 3.5 | < 0.05 in favor of IDeg | 0.2 vs. 0.2 U/kg/day | 0.78 vs. 0.44 U/kg/day | < 0.0001 in favor of Gla-100 |
Malone, 2005 [62] | 0.82 vs. -0.06 | 0.001 in favor of Gla-100 | 0.27 vs. 0.27 U/kg/day | 0.42 vs. 0.36 U/kg/day | < 0.001 in favor of Gla-100 |
Insulin Intensification
Gla-100 vs. NPH Insulin
Author, year | Study duration (months) | Overall hypoglycemia | Intergroup p value | Nocturnal hypoglycemia | Intergroup p value | Severe hypoglycemiaa | Intergroup p value |
---|---|---|---|---|---|---|---|
Gla-100 vs. NPH insulin | |||||||
Betonico, 2019 [72] | 9–12 | 4.9 vs. 6.3 events / patient | - | 0.5 vs. 1.5 events / patient | 0.047 | 0.7 vs. 1.03 events/patient | – |
Rosenstock, 2001 [73] | 6–9 | 61.4 vs. 66.8 | - | 31.3 vs. 40.2 | 0.02 | 6.6 vs. 10.4 | – |
Gla-100 vs. premixed insulin | |||||||
Aschner, 2015 [74] | 6–9 | 1.20 vs. 3.40 episodes/ PYE | – | 0.35 vs. 1.01 episodes / PYE | < 0.05 | – | – |
Ito H, 2014 [71] | 3–6 | – | – | – | – | – | – |
Tinahones, 2014 [75] | 6–9 | 16.51 vs. 13.07 episodes / PYE | – | 1.54 vs. 1.82 episodes / PYE | – | 0.04 vs. 0.0 episodes / PYE | – |
Tentolouris N, 2013 [83] | > 12 | 0.705 vs. 0.757 episodes / patient/year | – | 0.053 vs. 0.076 episodes / patient/year | – | 0.007 vs. 0.017 episodes / patient / year | – |
Jain, 2010 [67] | 6–9 | 2.19 vs. 1.57 episodes / Patient/ month | 0.022 | 46.7 vs. 46.9% of the population | – | 2.1 vs. 3.4% of the population | – |
Rosenstock, 2008 [76] | 6–9 | 48.70 vs. 51.20 | – | 4.78 vs. 6.17 | – | 0.10 vs. 0.04 | – |
Joshi, 2005 [70] | 3–6 | 58.08 vs. 16.07 | < 0.05 | – | – | – | – |
Fritsche, 2010 [64] | > 12 | 13.99 events per patient-year vs. 18.54 events per patient-year | NS | 2.28 vs. 2.37 events per patient-year | NS | 0.11 vs. 0.22 events per patient-year | NS |
Levin, 2011 [77] | 6–9 | 36 vs. 42% | NS | – | – | – | – |
Bowering, 2012 [78] | 9–12 | 1.96 events per patient per 30 days vs. 1.71 events per patient per 30 days | NS | 0.85 events per patient per 30 days vs. 0.67 events per patient per 30 days | NS | 2.8 vs. 3.4% | NS |
Miser, 2010 [63] | 6–9 | Intensification arm A – 11.2 (44.8) vs. 10.1 (21.8) Intensification arm B – 12.1 (28.2) vs. 11.1 (20.4) events / PYE | NS | Intensification arm A – 3 (13.6) vs. 2.5 (7.0) Intensification arm B – 2.4 (6.1) vs. 2.5 (8.1) events / PYE | NS | Intensification arm A – 3 (13.6) vs. 2.5 (7.0) Intensification arm B – 2.4 (6.1) vs. 2.5 (8.1) | |
Riddle, 2014 [66] | > 12 | G + 1 vs. G + 3 vs. PM (2 +) – 7.1 (0.9) vs. 7.2 (1) vs. 12.2 (1.7) | 0.0013 for G + 1 vs. PM (2 +); 0.0016 for G + 3 vs. PM (2 +) | – | – | G + 1 vs. G + 3 vs. PM (2 +) – 0.1 (0) vs. 0.2 (0.1) vs. 0.2 (0.1) | NS for all comparisons |
Vora, 2015 [65] | 6–9 | 15.3 events / PYE vs. 18.2 events / PYE | NS | 5.7 events / PYE vs. 3.6 events / PYE | 0.019 | – | – |
Jia, 2015 [79] | 6–9 | 0.41 (0.67) events / patient / 30 days vs. 0.47 (1.04) events / patient / 30 days | NS | 0.05 (0.21) events / patient / 30 days vs. 0.03 (0.09) events / patient / 30 days | NS | 0 vs. 0 | NS |
Giugliano, 2014 [68] | 9–12 | 8.13 (13.45) events / PYE vs. 9.63 (19.31) events / PYE | NS | 1.09 (3.25) events / PYE vs. 1.91 (5.20) events / PYE | 0.018 | 0.12 (0.80) events / PYE vs. 0.09 (0.74) events / PYE | NS |
Gla-100 vs. second-generation basal insulins | |||||||
Hollander, 2015 [80] | > 12 | 9.84 vs. 12.76 episodes / PYE | 0.011 | 1.27 vs. 1.77 episodes / PYE | 0.016 | 0.05 vs. 0.06 episodes / PYE | – |
Riddle, 2014 [81] | 6–9 | 26.37 vs. 28.08 episodes / PYE | – | 3.32 vs. 4.57 episodes / PYE | 0.0045 | 0.27 vs. 0.24 episodes / PYE | – |
Gla-100 vs. co-formulations | |||||||
Philis-Tsimikas A, 2019 [82] | 9–12 | 2.87 vs. 3.43 episodes / PYE | – | 0.6 vs. 1.01 episodes / PYE | < 0.05 | 0.037 vs. 0.048 episodes / PYE | – |
Gla-100 vs. other basal insulins | |||||||
Raskin, 2009 [84] | 6–9 | 19.30 vs. 17.94 episodes / PYE | – | 4.23 vs. 3.38 episodes / PYE | – | 0.09 vs. 0.12 episodes / PYE | – |
Hollander, 2008 [84] | > 12 | 12.55 vs. 9.30 episodes / PYE | NS | 2.88 vs. 2.4 episodes / PYE | NS | – | – |
Author, year | Weight change from baseline; mean | Intergroup p value | Baseline insulin dose | Post-treatment insulin dose | Intergroup p value |
---|---|---|---|---|---|
Gla-100 vs. NPH insulin | |||||
Betonico, 2019 [72] | – | – | – | 0.31 vs. 0.34 U/kg/day | – |
Rosenstock, 2001 [73] | 0.4 vs. 1.4 | 0.0007 | – | 0.75 vs. 0.75 U/kg/day | – |
Gla-100 vs. premixed insulin | |||||
Aschner, 2015 [74] | 1.1 vs. 1.4 | – | 0.17 vs, 0.17 U/kg/day | 0.60 vs. 0.81 U/kg/day | – |
Ito H, 2014 [71] | – | – | 26.8 | 25.8 | – |
Tinahones, 2014 [75] | 1.13 vs. 0.5 | 0.018 in favor of basal bolus | 33.8 vs. 33.5 U/day | 39.8 vs. 37.4 U/day | – |
Tentolouris N, 2013 [83] | 0.734 vs. 0.121 | – | 0.61 vs. 0.56 U/kg/day | 0.65 vs. 0.53 U/kg/day | < 0.001 in |
Jain, 2010 [67] | 3.19 vs. 3.09 | – | – | 0.51 vs. 0.57 U/kg/day | 0.017 |
Rosenstock, 2008 [76] | 4.0 vs. 4.5 | – | 52.0 vs. 55.0 U/day | 123.0 vs. 146.0 U/day | 0.002 |
Joshi, 2005 [70] | – | – | 38.23 vs. 57.39 U/day | 40.19 vs. 52.77 U/day | – |
Fritsche, 2010 [64] | 3.6 vs. 2.2 | < 0.0001 | 52.4 vs. 58.3 U/day | 98 vs. 91.3 U/day | < 0.0001 |
Levin, 2011 [77] | 2.40 vs. 2.35 | 0.03 | 76.92 vs. 77.65 U/day | 78.31 vs. 90.06 U/day | NS |
Bowering, 2012 [78] | 2.92 vs. 2.78 | NS | – | 0.71 vs. 0.71 U/kg/day | NS |
Miser, 2010 [63] | Intensification arm A – 0 vs. 2 Intensification arm B – 0 vs. 2 | NS | Intensification arm A – 41 (24.3) vs. 41.9 (24.4) Intensification arm B – 50 (24) vs. 49.9 (21.3) U/day | Intensification arm A – 69.4 (44.4) vs. 71.1 (39.4) Intensification arm B – 74.4 (36.1) vs. 73.9 (39.2) U/day | NS |
Riddle, 2014 [66] | G + 1 vs. G + 3 vs. PM (2 +) – 5.0 (6.5) vs. 6.8 (7.6) vs. 6.4 (6.9) | 0.024 for G + 1 and G + 3 vs. PM (2 +) | – | G + 1 vs. G + 3 vs. PM (2 +) – 0.92 (0.47) vs. 1.05 (0.73) vs. 1.04 (0.66) U/kg/day | NS for all comparisons |
Vora, 2015 [65] | 2.06 vs. 2.5 | NS | – | – | NS |
Jia, 2015 [79] | 0.7 vs. 0.8 | NS | 0.62 (0.21) vs. 0.63 (0.20) U/kg/day | 0.76 (0.27) vs. 0.74 (0.25) U/kg/day | NS |
Giugliano, 2014 [68] | 2.32 (3.7) vs. 2.31 (3.3) | NS | – | 0.57 (0.39) vs. 0.56 (0.32) U/kg/day | NS |
Gla-100 vs. second-generation basal insulins | |||||
Hollander, 2015 [80] | 4.4 vs. 4.0 | – | – | 0.71 vs. 0.76 U/kg/day | – |
Riddle, 2014 [81] | 0.9 vs. 0.9 | – | 0.67 (vs. 0.67 U/kg/day | 0.97 vs. 0.88 U/kg/day | – |
Gla-100 vs. co-formulations | |||||
Philis-Tsimikas A, 2019 [82] | 2.4 vs. 2.5 | – | 35.2 vs. 34.6 U/day | 83.4 vs. 89.3 U/day | < 0.05 in favor of IDegAsp |
Gla-100 vs. other basal insulins | |||||
Raskin, 2009 [84] | 1.2 vs. 2.7 | 0.001 in favor of IDet | 0.2 vs. 0.2 U/kg/day | 0.81 vs. 0.75 U/kg/day | – |
Hollander, 2008 [85] | 3.8 vs. 2.8 | < 0.05 | – | – | NS |