Table 1.
Study characteristics
| Treatment comparison | Author (year) | Study population | Follow-up period | Treatment group | Treatment group population | Age | Gender | Fasting glucose | HbA1c | Insulin dose |
|---|---|---|---|---|---|---|---|---|---|---|
| Basal-bolus 1× vs premix BID | Riddle (2014) | 588 | Baseline—60 weeks | Glargine 100 U/mL QD + glulisine 1× (++ OADs) | 194 | Mean 53.8 (± SD 9.08) | Female—106 (56.4%) | Mean 11.0 mmol (± SD 3.9) (plasma) | Mean 9.4% (± SD 1.7) | Mean 0.11 U/kg, population n = 189, mITT |
| Aspart 70/30 BID (++ OADs) | 194 | Mean 53.7 (± SD 10.7) | Female—109 (56.2%) | Mean 11.3 mmol (± SD 3.6) (plasma) | Mean 9.3% (± SD 1.6) | Mean 0.11 U/kg, population n = 181, mITT | ||||
| Basal-bolus 1× vs premix BID | Tinahones (2014) | 478 | Baseline—24 weeks | Glargine 100 U/mL QD + lispro 1× (++ metformin and/or pioglitazone) | 240 | Mean 57.7 (± SD 9.1) | Female—142 (59.2%) | Mean 6.2 mmol (± SD 1.8) (plasma) | Mean 8.6% (± SD 0.7) | Mean 33.5 U (± SD 17.1) |
| Lispro 75/25 BID (++ metformin and/or pioglitazone) | 236 | Mean 57.4 (± SD 9.9) | Female—120 (50.8%) | Mean 6.4 mmol (± SD 2) (plasma) | Mean 8.7% (± SD 0.8) | Mean 33.8 U (± SD 18.7) | ||||
| Basal-bolus 1× vs premix BID | Vora (2015) | 335 | Baseline—24 weeks | Glargine 100 U/mL QD + glulisine 1× (++ metformin) | 170 | Mean 61.6 (± SD 8) | Female—47 (27.6%) | Mean 6.1 mmol (± SD 1.64) (plasma), population n = 170 participant | Mean 8.6% (± SD 0.9), population n = 170 participant | Mean 45 U |
| Aspart 70/30 BID (++ metformin) | 164 | Mean 61.6 (± SD 8.9) | Female—45 (27.4%) | Mean 6.04 mmol (± SD 1.6) (plasma), population n = 165 participant | Mean 8.6% (± SD 0.9), population n = 165 participant | Mean 42 U | ||||
| Basal-bolus 3× vs premix BID | Fritsche (2010) | 310 | Baseline—52 weeks | Glargine 100 U/mL QD + glulisine 0–3× (++ metformin) | 153 | Mean 60.2 (± SD 7.5) | Female—70 (45.8%) | Mean 9.9 mmol (± SD 3) (plasma) | Mean 8.62% (± SD 0.83) | Mean 52.4 IU (± SD 23.5) |
| NPH 70/30 BID (++ metformin) | 157 | Mean 60.9 (± SD 7.8) | Female—82 (52.2%) | Mean 9.7 mmol (± SD 3.3) (plasma) | Mean 8.51% (± SD 0.86) | Mean 58.3 IU (± SD 26.7) | ||||
| Basal-bolus 3× vs premix BID | Liebl (2009) | 719 | Baseline—26 weeks | Detemir QD + aspart 3× | 537 | Mean 60.3 (± SD 9.2) | Female—231 (43%) | Mean 11.21 mmol/L (± SD 3.2) (plasma) | Mean 8.52% (± SD 1.13) | N/A |
| Aspart 70/30 BID | 178 | Mean 61.7 (± SD 9.2) | Female—66 (37%) | Mean 10.95 mmol/L (± SD 2.9) (plasma) | Mean 8.4% (± SD 1.03) | N/A | ||||
| Basal-bolus 3× vs premix TID | Jia (2015) | 402 | Baseline—24 weeks | Glargine 100 U/mL QD + lispro 3× (++ OADs) | 202 | Mean 58.1 (± SD 9.07) | Female—93 (46.04%) | Mean 11 mmol (± SD 3.9) (plasma) | Mean 9.8% (± SD 3.13) | Mean 0.62 U/kg (± SD 0.21) |
| Lispro 50/50 BID + lispro 75/25 QD (++ OADs) | 197 | Mean 59.1 (± SD 9.1) | Female—95 (48.22%) | Mean 11.3 mmol (± SD 3.6) (plasma) | Mean 9.99% (± SD 2.69) | Mean 0.63 U/kg (± SD 0.2) | ||||
| Basal-bolus 3× vs premix TID | Rosenstock (2008) | 374 | Baseline—24 weeks | Glargine 100 U/mL QD + lispro 3× (++ OADs) | 187 | Mean 54 (± SD 9.2) | Female—89 (48%) | Mean 10.08 mmol (± SD 3.32) (plasma) | Mean 8.89% (± SD 1.09) | Mean 0.56 U/kg (± SD 0.27) |
| Lispro 50/50 TID (++ OADs) | 187 | Mean 55.4 (± SD 9.8) | Female—88 (47%) | Mean 9.54 mmol/L (± SD 3.32) (plasma) | Mean 8.83% (± SD 1.04) | Mean 0.53 U/kg (± SD 0.21) | ||||
| Basal-bolus stepwise vs premix stepwise | Bowering (2012) | 426 | Baseline—48 weeks | Glargine 100 U/mL QD + lispro 1–3× (++ metformin) | 212 | Mean 56.29 (± SD 9.35) | Female—107 (50.5%) | NA | Mean 9.03% (± SD 1.05) | Mean 10 U |
| Lispro 75/25 1-3× (++ metformin ± sulfonylurea) | 211 | Mean 56.68 (± SD 8.03) | Female—118 (55.9%) | NA | Mean 8.98% (± SD 1.04) | Mean 10 U | ||||
| Basal-bolus stepwise vs premix stepwise | Giugliano (2014) | 344 | Baseline—48 weeks | Glargine 100 U/mL QD + lispro 1–3× (++ OADs) | 173 | Mean 54.2 (± SD 8.6) | Female—92 (53%) | Mean 9.6 mmol/L (± SD 2.2) (plasma) | Mean 9.07% (± SD 0.99) | NA |
| Lispro 75/25 or lispro 50/50 1–3× (++ OADs) | 171 | Mean 54.3 (± SD 8.9) | Female—84 (49%) | Mean 9.4 mmol/L (± SD 2.2) (plasma) | Mean 8.98% (± SD 0.95) | NA | ||||
| Basal-bolus stepwise vs premix stepwise | Jain (2010) | 484 | Baseline—36 weeks | Glargine 100 U/mL QD + lispro ≤ 3× (++ OADs) | 195 | Mean 59.9 (± SD 9.6) | Female—94 (48.2%) | Mean 9.6 mmol/L (± SD 12.57, SE 0.9) (blood) | Mean 9.3% (± SD 1.2) | NA |
| Lispro 50/50 1–3× (++ OADs) | 188 | Mean 58.9 (± SD 8.8) | Female—102 (54.3%) | Mean 10.2 mmol/L (± SD 12.34, SE 0.9) (blood) | Mean 9.5% (± SD 1.2) | NA | ||||
| Basal-bolus stepwise vs premix stepwise | Jin (2016) | 161 | Baseline—24 weeks | Glargine 100 U/mL QD + glulisine 0–2× | 78 | Mean 59.45 (± SD 10.03) | Female—39 (50%) | Mean 105.1 mg/dL (5.83 mmol/L) (± SD 20.26) (plasma) | Mean 8.48% (± SD 0.74) | Mean 35.53 U (± SD 13.32) |
| Aspart 70/30 BID | 82 | Mean 59.5 (± SD 8.72) | Female—43 (52.44%) | Mean 107.82 mg/dL (5.98) mmol/L) (± SD 22.84) (plasma) | Mean 8.31% (± SD 0.74) | Mean 12.49 U (± SD 2.97) | ||||
| Basal-bolus stepwise vs premix stepwise | Linjawi (2017) | 335 | Baseline—32 weeks | Glargine 100 U/mL QD + insulin aspart (++ metformin + sulfonylurea) | 167 | Mean 56.6 (± SD 10.4) | Female—90 (53.9%) | Mean 9.6 mmol/L (± SD 2.3) (plasma) | Mean 8.2% (± SD 0.7) | Mean 0.127 U/kg |
| Aspart 70/30 QD-TID (++ metformin + sulfonylurea) | 168 | Mean 56.6 (± SD 10.4) | Female—79 (47%) | Mean 9.7 mmol/L (± SD 2.7) (plasma) | Mean 8.3% (± SD 0.7) | Mean 0.157 U/kg | ||||
| Basal-bolus stepwise vs premix stepwise | Malek (2015) | 403 | Baseline—50 weeks | Detemir QD + metformin (++ aspart 1–3×) | 200 | Mean 59.45 (± SD 10.03) | Female—113 (56.5%) | Mean 9.52 mmol/L (plasma) | Mean 8.7% (± SD 1.1) | Mean 0.1 U/kg (± SD 13.32) |
| Aspart 70/30 QD-TID + metformin | 203 | Mean 52.6 (± SD 10.1) | Female—128 (63.1%) | Mean 10.07 mmol/L (plasma) | Mean 8.6% (± SD 1) | Mean 0.1 U/kg (± SD 2.97) | ||||
| Basal ± OAD vs premix BID ± OAD | Al-Shaikh (2006) | 221 | Baseline—6 months | Glargine 100 U/mL QD (++ metformin + sulfonylurea) | 111 | NA | NA | NA | Mean 11.4% (range 8–16.4) | NA |
| NPH 70/30 BID | 110 | NA | NA | NA | Mean 11.2 | NA | ||||
| Basal ± OAD vs premix BID ± OAD | Buse (2009) | 2091 | Baseline—24 weeks | Glargine 100 U/mL QD (++ OADs) | 1046 | Mean 57 (± SD 10) | Female—494 (47.2%) | Mean 10.9 mmol/L (± SD 3.1) (plasma) | Mean 9% (± SD 1.2) | NA |
| Lispro 75/25 BID (++ OADs) | 1045 | Mean 57 (± SD 10.0) | Female—493 (47.2%) | Mean 10.7 mmol/L (± SD 3) (plasma) | Mean 9.1% (± SD 1.3) | NA | ||||
| Basal ± OAD vs premix BID ± OAD | Cao (2017) | 72 | Baseline—16 weeks | Glargine 100 U/mL QD + sitagliptin | 33 | Mean 52.1 (± SD 9.6) | Female—15 (46.6%) | Mean 9.11 mmol/L (± SD 2.43) (plasma) | Mean 8.07% (± SD 0.91) | NA |
| Aspart 70/30 BID | 32 | Mean 49.8 (± SD 11.2) | Female—16 (49.8%) | Mean 10.12 mmol/L (± SD 2.13) (plasma) | Mean 8.23% (± SD 0.81) | NA | ||||
| Basal ± OAD vs premix BID ± OAD | Holman (2009) | 708 | Baseline—3 years | Detemir QD | 234 | N/A | N/A | N/A | Mean 8.5% (95% CI 8.4–8.62) | Mean 0.173 U/kg (95% CI 0.156–0.191) |
| Aspart 70/30 BID | 235 | N/A | N/A | N/A | Mean 8.6% (95% CI 8.49–8.7) | Mean 0.182 U/kg (95% CI 0.165–0.208) | ||||
| Basal ± OAD vs premix BID ± OAD | Janka (2005) | 364 | Baseline—24 weeks | Glargine 100 U/mL QD + glimepiride (++ metformin) | 177 | Mean 60.9 years (± SD 8.7) | Female—69 (39%) | Mean 9.5 mmol/L (± SD 1.9) (blood) | Mean 8.85% (± SD 0.98) | Mean 9.9 U (± SD 2.6) |
| Human premixed 70/30 BID | 187 | Mean 60.4 years (± SD 9.1) | Female—80 (43%) | Mean 9.6 mmol/L (± SD 2.1) (blood) | Mean 8.83% (± SD 0.87) | Mean 20.6 U | ||||
| Basal ± OAD vs premix BID ± OAD | Kann (2006) | 258 | Baseline—26 weeks | Glargine 100 U/mL QD + glimepiride | 127 | Mean 61 years (± SD 8.9) | Female—65 (51.2%) | N/A | Mean 8.9% (± SD 1.3) | Mean 0.2 U/kg |
| Aspart 70/30 BID + metformin | 128 | Mean 61.5 years (± SD 9.3) | Female—59 (46.1%) | N/A | Mean 9.21% (± SD 1.4) | Mean 0.2 U/kg | ||||
| Basal ± OAD vs premix BID ± OAD | Ligthelm (2011) | 280 | Baseline—24 weeks | Glargine 100 U/mL QD + glimepiride (++ metformin + insulin secretagogues ± thiazolidinedione) | 143 | Mean 53.5 years (± SD 10.6) | Female—59 (41.3%) | Mean 174.6 mg/dL (9.69 mmol/L) (± SD 60) (plasma), population, n = 127, ITT | Mean 9% (± SD 1.2) | Mean 0.39 U/kg (± SD 0.22), population, n = 141, safety |
| Aspart 70/30 BID (++ metformin ± thiazolidinedione) | 137 | Mean 51.9 years (± SD 10.2) | Female—62 (45.3%) | Mean 179.7 mg/dL (9.97 mmol/L) (± SD 67.7) (plasma), population, n = 132, ITT | Mean 9% (± SD 1) | Mean 0.46 U/kg (± SD 0.23), population, n = 138, safety | ||||
| Basal ± OAD vs premix BID ± OAD | Raskin (2005) | 233 | Baseline—28 weeks | Glargine 100 U/mL QD (++ metformin ± thiazolidinedione ± pioglitazone) | 116 | Mean 52.3 years (± SD 9.8) | Female—51 (44%) | Mean 243 mg/dL (13.49 mmol/L) (± SD 68.8) (plasma) | Mean 9.8% (± SD 1.4) | Mean 0.13 U/kg (± SD 0.03) |
| Aspart 70/30 BID (++ metformin ± thiazolidinedione ± pioglitazone) | 117 | Mean 52.6 years (± SD 10.6) | Female—55 (47%) | Mean 252 mg/dL (13.99 mmol/L) (± SD 67.4) (plasma) | Mean 9.7% (± SD 1.5) | Mean 0.14 U/kg (± SD 0.03) | ||||
| Basal ± OAD vs premix BID ± OAD | Zhou (2015) | 105 | Baseline—12 weeks | Glargine 100 U/mL QD + gliclazide | 52 | Mean 55.54 years (± SD 5.88) | Female—24 (46.15%) | Mean 10.49 mmol/L (± SD 2.01) (plasma) | Mean 8.48% (± SD 0.69) | Mean 0.19 U/kg (± SD 0.02) |
| Human insulin 70/30 BID | 53 | Mean (54.39 yr (± SD 6.86) | Female—27 (50.94%) | Mean 10.16 mmol/L (± SD 2.17) (plasma) | Mean 8.55% (± SD 0.79) | Mean 0.41 U/kg (± SD 0.1) |
++ Background therapy + concurrent/concomitant, ± part of the population received but the rest did not receive the additional intervention, QD once-daily, BID twice daily, TID three times daily, OAD/OADs oral antidiabetic drugs, CI confidence interval, SD standard deviation, SE standard error, CI confidence interval, ITT intent-to-treat, mITT modified intent-to-treat