Table 9: Comparing pre-mixed and basal insulin initiation regimens in T2DM.
Study | Population criteria | Types of insulin used | Effect on HbA1c | Adverse effects |
Giugliano, et al. [23] Meta-analysis of 16 RCTs | 7759 patients with T2DM where RCTs were for at least 12 weeks | Biphasic premixed insulins, short-acting prandial insulins and basal insulin | Premixed insulin lead to OR 1.88 to achieve HbA1c < 7% compared with basal insulin | Premixed insulin was associated with 0.34 more hypoglycaemic events/patient/30 days than basal insulin
1 kg more weight gain was seen with premixed insulins |
Janka, et al. [42] Multinational, multicentre, open parallel group study | 371 insulin naïve individuals with T2DM and HbA1c between 7.5-10% | Once daily morning insulin glargine and OHAs compared with 30% regular/70% human NPH insulin twice daily alone | Reduction of 1.64% with glargine compared to reduction of 1.31% premixed insulin (p = 0.0003)
Glargine led to 45.5% of patients with HbA1c ≤ 7.0% compared to 28.6% without confirmed nocturnal hypoglycaemia (p = 0.0013) |
4.07 hypoglycaemic events/patient year with glargine
9.87 hypoglycaemic events/patient year with premixed insulin (p < 0.0001) |
Initiate study [43] 28 week parallel-group study | 233 insulin naïve patients with HbA1c ≥ 8.0% on OHAs
Metformin was titrated to 2550 mg/day before insulin initiation |
Premixed 70/30% twice daily insulin compared with glargine at bedtime | Mean HbA1c was 6.91% with premixed versus 7.41% with basal insulin (p < 0.01)
HbA1c reduced by 2.79% with premixed compared to 2.36% reduction with basal insulin (p < 0.01) especially if HbA1c was > 8.5% HbA1c target of ≤ 6.5% was achieved in 14% more patients with pre-mixed (p < 0.05) |
2.7 more hypoglycaemic episodes/year seen with premixed versus basal insulin (p < 0.05)
1.9 kg more weight gain with premixed versus basal insulin (p < 0.01) |
Durable trial [44] 24 week randomised, multicentre, multinational, open parallel trial | 2091 insulin naïve adults patients with T2DM with HbA1c > 7% on at least 2 OHAs for 90 days | Twice daily premixed lispro protamine suspension 75% and 25% lispro or daily glargine with continuation of OHAs in both groups | 7.2% people achieved HbA1c target < 7% with premixed (p < 0.001)
Premixed insulin showed 1.8% reduction compared to 1.7% seen with glargine (p = 0.005) |
1.1 kg more weight gain seen with premixed rather than basal insulin (p < 0.0001)
4.9 more hypoglycaemic episodes/patient/year with premixed compared to basal insulin (p = 0.007) but fewer nocturnal hypoglycaemia (p = 0.007) |