Table 3.
Studies Evaluating Timing of Insulin Glargine Administration
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Change from baseline |
Frequency of hypoglycemia (episodes/patient–month, % patients) |
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| Reference | Design | No. patients | Trial duration | Treatments | A1c % | FBG (mmol/L) | Symptomatic | Nocturnal | Comments |
| Hamann 200329 (Study 4007) |
Open-label, multicenter, parallel-group trial | 378 | 24 weeks treatment | Breakfast glargine + lispro Dinnertime glargine + lispro Bedtime glargine + lispro |
−0.2% (baseline 7.6%) −0.1 % (baseline 7.5%) −0.1% (baseline 7.6%) P = NS |
+ 0.1 ± 2.6 −1.2 ± 2.7 −1.3 ± 2.5 P = NS |
92.6% 93.8% 96.9% P = NS |
59.5%, P = 0.29 vs bedtime and dinner time 71.9%, P = 0.0013 vs breakfast 77.5% |
No clinically relevant difference in efficacy when glargine administered before breakfast, before dinner, or at bedtime |
| Ashwell 200628 | Three-way cross over study to determine the optimal timing of injection of once-daily glargine in people using lispro at mealtimes | 23 | 16 weeks | Lunchtime glargine + lispro Dinnertime glargine + lispro Bedtime glargine + lispro |
Endpoint: 9.2 ± 0.3% Endpoint: 8.2 ± 0.3% Endpoint: 8.0 ± 0.3% P = 0.016 |
8.6 ± 0.7 6.4 ± 0.7 6.4 ± 0.8 P = 0.051 |
9.4 ± 0.9 4.9 ± 0.9 7.4 ± 1.1 P = 0.007 |
9.1 ± 0.6 7.8 ± 0.6 6.7 ± 0.6 P = 0.023 |
BG levels rise around the time of glargine administration, whatever the time. Bedtime dosing leads to hyperglycemia in the early part of the night which is improved by giving insulin glargine at lunch time or dinner time |
| Grimaldi 200738 (Study 4024) |
Open-label, multicenter, parallel-group, non-inferiority study | 1178 | 26 weeks | Dinnertime glargine (18:30–21:00) + FAA (75%) or RHI (25%) Bedtime glargine (22:00 – 24:00) + FAA or RHI |
−0.25 ± 0.66% (baseline 8.01%) −0.24 ± 0.76% (baseline 8.08%) P = NS |
NR NR P = NS |
Severe: 6.85% Severe: 5.69% P = NS |
NR NR |
No difference in A1C variation, FBG decrease, severe hypoglycemia or weight change: equivalence between regimens shown |
FBG = fasting blood glucose; NS = not significant; NR = not reported; FAA = fast-acting analogue; RHI = regular human insulin; BG = blood glucose; SMBG = self-monitored blood glucose; od = once-daily; bd = twice-daily; NPH = neutral protamine Hagedorn insulin; glargine = insulin glargine.