Table 3.
Nocturnal Hypoglycemia and Glycemic Control in Clinical Trials Comparing Insulin Analogs vs Human Insulin (T1DM)
| Reference | Length | Treatments (Regimen) [N] | Nocturnal Hypoglycemia (P value)a | % A1Cb (P value) | |
|---|---|---|---|---|---|
| Fulcher[57] | 30 wks | Glargine (HS) + lispro (PP) [62] | 1.77c;d (.04) | 0.22c;e (.02) | −1.04 (<.01) −0.51 |
| NPH (HS) + lispro (PP) [63] | 2.30c;d | 0.37c;e | |||
| Home[58] | 28 wks | Glargine (HS) + RHI (PP) [292] | 61%f | +0.21 | |
| NPH (HS or AM+HS) + RHI (PP) [293] | 61%f | +0.10 | |||
| Raskin[59] | 16 wks | Glargine (HS) + lispro (PP) [310] | 69%f | 12.3%g | −0.1 |
| NPH (HS or AM+HS) + lispro (PP) [309] | 63%f | 12.0%g | −0.1 | ||
| Ratner[60] | 28 wks | Glargine (HS) + RHI (PP) [256] | 18.2%f (.0116) | 65.1h (<.05) | −0.16 −0.21 |
| NPH (HS or AM+HS) + RHI (PP) [262] | 27.1%f | 101.2h | |||
| Ashwell[62] | 32 wks (16 × 2 crossover) | Glargine (PM) + lispro (PP) [51] | 41%f, Mo 1 (.001) | 65%f, Mos 2-4 (.013) | 7.5i (<.001) |
| NPH (PM or AM+PM) + RHI (PP) [51] | 62%f, Mo 1 | 82%f, Mos 2–4 | 8.0i | ||
| Porcellati[63] | 1 year | Glargine (AD) + lispro (PP) [61] NPH 4 times daily + lispro (PP) [60] | 1.2j (<.05) 3.2j | −0.4 (<.05) 0.0 | |
| Hermansen[64] | 18 wks | Detemir (AM + HS) + aspart (PP) [298] | 4.0k | −0.50 (<.001) −0.28 | |
| NPH (AM+HS) + RHI (PP) [297] | (<.001) 9.2k | ||||
| Home[65] | 16 wks | Detemir (AM + HS) + aspart (PP) [139] | 34%f (.035) | −0.85 | |
| Detemir Q12 hours + aspart (PP) [137] | 44%f | (.002)l (3-way) | −0.82 −0.65 (.027)n | ||
| NPH (AM+HS) + aspart (PP) [132] | 50%f (<.001)m | ||||
| Russell-Jones[66] | 6 mos | Detemir (HS) + RHI (PP) [491] | 70.6%f | −0.06 | |
| NPH (HS) + RHI (PP) [256] | Dete(Detemir risk 26% lower than NPH; .003) | +0.06 | |||
| 72.9%f | |||||
| Pieber[67] | 16 wks | Detemir (AM + AD) + aspart (PP) [139] | 60%f | −0.43 | |
| Detemir (AM + HS) + aspart (PP) [132] | 51%f | −0.49 | |||
| NPH (AM+HS) + aspart (PP) [129] | 60%f | −0.39 | |||
| Kolendorf[68] | 32 wks (16 × 2 crossover) | Detemir (AM + HS) + aspart (PP) [125] | 6k (<.0001) | 3.4k;g (<.001) | −0.3 |
| NPH (AM+HS) + aspart (PP) [128] | 12k | 6.9k;g | −0.3 | ||
| Pieber[69] | 26 wks | Detemir (AM + AD) + aspart (PP) [161] | Detemir had 32% lower risk than glargine (<.05) | −0.6 | |
| Glargine (HS) + aspart (PP) [159] | −0.6 | ||||
| Pediatric Parallel-Group Comparative Trials | |||||
| Murphy[70] | 32 wks (16 × 2 crossover) Peds ages 12-18 | Glargine (HS) + lispro (PP) [25] | 8 of 25 nights (<.05) 14 of 25 nights | 8.7i 9.1i | |
| NPH (HS) + RHI (PP) [25] | |||||
| Schober[72] | 28 wks; Peds ages 5-16 | Glargine (HS) + RHI (PP) [174] | 12.6%f 17.7%f | +0.28 | |
| NPH (HS or AM+HS) + RHI (PP) [175] | +0.27 | ||||
| Robertson[71] | 26 wks; Peds aged 11.9 ± 2.8 yrs | Detemir (QD or BID) + aspart (PP) [232] | 4.5k (.011) | 8.0 at end | |
| NPH (QD or BID) + aspart (PP) [115] | 7.1k | 8.0 at end | |||
Analytic methods for event comparisons differ from trial to trial; P values are listed when comparison is significant
A1C values are change from baseline unless otherwise indicated
events per 100 patient-days
moderate
severe
patients with 1 or more episode
patients with episodes confirmed with blood glucose measurements
episodes per 100 patient-years
A1C value at end of treatment
episodes/patient/month
episodes/patient-year
ANOVA comparison of 3 treatment groups together
compared with AM + HS detemir
compared with pooled detemir groups.
T1DM = type 1 diabetes mellitus; N = number of patients; HS = at bedtime; PP = preprandial; RHI = regular human insulin; AD = dinnertime; M = moderate; S = severe; QD = once daily; BID = twice daily; RR = relative risk. Method of literature review and selection of trials included: Table 3 & Table 4 include data identified by searching PubMed, Adis, and BIOSIS literature databases. English-language clinical trials published between 2000 and 2006 using the following search strategy were identified: “(detemir OR glargine) AND nocturnal AND (hypoglycemia OR hypoglycaemia) AND diabetes.” Further, to capture trials that may not have specified “nocturnal” in the title or abstract text but still reported nocturnal hypoglycemia data, a supplemental search of PubMed using “(detemir OR glargine) AND (nocturnal OR hypoglycemia OR hypoglycaemia) AND diabetes” was performed. Reviews from 2004 to 2006 were included and scanned to identify missing trials. Publications (n = 307: 151 PubMed; 104 Adis; 52 BIOSIS) were evaluated and exclusions were made as follows: duplication (or abstracts since published in full), review older than 2004, letters, commentaries, case reports, simulations, cost or economic evaluations, subgroup analyses, patient-information summaries, trials involving CSII, nonparallel comparisons (eg, to a prestudy period), trials <16 weeks' duration, comparisons to analog-containing premixes, conducted with noncommercially available analog formulations, or studies conducted with insulin preparations that are no longer commercially available.