Table 2.
Dose titration regimens for basal insulins
| Trial Acronym & Reference | Frequency of Insulin Adjustments | Monitored Variable | Measured FPG Level (mg/dl [mmol/l]) | Change in Insulin Dosage (U/day) |
|---|---|---|---|---|
| Tested with twice-daily exenatide | ||||
| Buse et al. [16]* | Weekly for 5 weeks then at least every other week | Mean FPG of prior 3–7 days | > 180 (> 10) 140–179 (7.8–9.9)† 120–139 (6.7–7.7)† 100–119 (5.6–6.6)† 73–99 (4.1–5.5) | ↑ 8 ↑ 6 ↑ 4 ↑ 2 No change |
| At least one FPG value since last assessment At least one FPG value since last assessment | 56–72 (3.1–4.0) < 56 (< 4.0) | ↓ 2 ↓ 4 | ||
| Not tested with twice-daily exenatide | ||||
| INITIATE‡ Raskin et al. [43] | Weekly for 12 weeks and then every 2 weeks thereafter | FPG on 3 preceding days | > 180 (> 10) 141–180 (7.8–10) 111–140 (6.2–7.8) 80–110 (4.4–6.2) < 80 (< 4.4) | ↑ 6–8† ↑ 4–6† ↑ 2–4† No change ↓ 2 |
| INSIGHT§ Gerstein et al. [41] | Daily | Daily FPG | > 99 (> 5.5) | ↑ 1 |
| LANMET¶ Yki-Jarvinen et al. [42] | Varied based on FPG readings | FPG on 3 consecutive mornings | > 180 (> 10) 99–180 (5.5–10) | ↑ 4 ↑ 2 |
| 4-T** Holman et al. [9] | Not specified | Twice-daily glucose | Fasting target: 72–99 mg/dl (4.0–5.5 mmol/l) Two-hourpostprandial target:90–126 mg/dl (5.0–7.0 mmol/l) | ↑ 10% or 4 U (whichever is greater) if the mean glucose reading for a given time point is > 72 mg/dl (> 4.0 mmol/l) above upper end of range†† Otherwise, ↑ 5% or 4 U (whichever is greater)†† ↓ By 10% or 4 U (whichever is the greater) in the presence of grade 3 hypoglycaemia or mean glucose readings < 56 mg/dl (< 3.1 mmol/l)†† Otherwise, ↓ 5% or 2 U (whichever is greater)†† |
| Rosenstock et al. [11]‡‡ | Weekly for 12 weeks and approximately every 3 weeks thereafter | FPG on 3 consecutive mornings | > 180 (> 10) 164–180 (9.1–10) 145–163 (8.1–9.0) 127–144 (7.1–8.0) 109–126 (6.1–7.0) 73–108 (4.1–6.0) | ↑ 12 ↑ 8§§ ↑ 6§§ ↑ 4§§ ↑ 2 No change |
| One FPG value One FPG value | 56–72 (3.1–4.0) < 56 (< 3.1) | ↓ 2 ↓ 4 | ||
FPG, fasting plasma glucose; ↑, increase by; ↓, decrease by.
Modified from Treat-to-Target protocol [10]. Trial compared glargine + exenatide vs. glargine + placebo. Insulin starting dosage was 10 U/day. Final mean FPG was 117 mg/dl (6.5 mmol/l) in the glargine + exenatide group and 118 mg/dl (6.6 mmol/l) in the glargine + placebo group.
†The increase in daily dose should not exceed more than 10 U/day or 10% of the current daily dose, whichever is greater.
‡Trial compared glargine vs. biphasic insulin aspart 70/30; final mean FPG was 117 mg/dl (6.5 mmol/l) in the glargine group.
§Trial compared glargine vs. conventional therapy; patients started with 10 units of insulin per day.
¶Trial compared glargine + metformin vs. NPH + metformin. The initial bedtime insulin dose was 10 U for all patients who were using metformin alone, and 20 U if the patients had used both sulfonylurea and metformin and sulfonylurea was stopped, as was mandated by the study design. Final mean FPG was 103 mg/dl (5.7 mmol/l) in the glargine group.
*Trial compared detemir vs. biphasic aspart vs. prandial insulin. Starting doses of insulin according to the following formulas: for men, [(FPG [mmol/l] − 5) × 2] × (weight [kg] ÷ [14.3 × height (m) − height (m)]; for women, [(FPG [mmol/l] − 5) × 2] × (weight [kg] ÷ (13.2 × height [m]) − height [m]). Final mean FPG was 112 mg/dl (6.2 mmol/l).
††The trial-management system suggested changes in insulin dosages according to the following rules. Maintain prebedtime insulin doses if more than 2/3 of prebreakfast and pre-evening meal glucose readings are within range. Increase prebedtime insulin dose (when no hypoglycaemia) if more than 1/3 of prebreakfast meal glucose readings remain high. Add a prebreakfast insulin injection if glucose readings are at target before breakfast, but not before the evening meal and nocturnal hypoglycaemia limits further prebedtime insulin dose increases. Decrease insulin doses in the presence of: (i) any Grade 2 or 3 hypoglycaemic episode at relevant time points; and (ii) mean glucose readings< 70 mg/dl (< 3.9 mmol/l) at relevant time points.
‡‡Trial compared detemir vs. glargine. Basal insulin was initiated at 12 U/day. Final mean FPG was 131 mg/dl (7.27 mmol/l) in the once-daily detemir group and 126 mg/dl (6.98 mmol/l) in the glargine group.
§§Add 2 units if no response to previous insulin adjustment; no response is defined as occurring if the average self-monitored plasma glucose level is increased and/or within the same range as the last contact.