Meta-analyses of clinical trials comparing CSII with traditional
insulin injections usually show a small, but significant advantage of CSII with respect to HbA1c and risk of severe
hypoglycemia. On the other hand, CSII is associated with a small, but relevant risk of
ketoacidosis, mainly due to malfunction of
insulin pump and/or
catheter occlusion. During last time, the technology of
insulin pumps and infusion sets has improved as the profound evolution in type and schemes with traditional
insulin injections. Aim of the present study is to update previous meta-analyses comparing CSII with traditional
insulin injections in subjects with
type 1 diabetes. Specific subgroup analyses were designed for assessing the effects of CSII in comparison with basal-bolus MDI, with short-acting analogues as bolus and long-acting analogues as basal
insulin. In addition, an exploratory analysis was performed to verify the effect of CSII in
insulin-naïve patients with
type 1 diabetes. The present analysis includes all randomized clinical trials comparing CSII with traditional
injections in
type 1 diabetes, with a duration of at least 12 weeks. Animal studies were excluded, whereas no language or date restriction was imposed. If duplicate publications of a single trial were present, the paper containing more adequate information was considered as principal publication. In trials comparing CSII with basal-bolus MDI, performed before the introduction of rapid-acting analogues, regular human
insulin was used for CSII, and as prandial
insulin in control groups. CSII was associated with a significant reduction of A1c, in comparison with MDI, irrespective of the use of either human
insulin or rapid-acting analogues. However, in trials with rapid-acting analogue the advantage of CSII was significantly smaller than in trials with regular human
insulin (HbA1c difference: - 0.29[- 0.46; - 0.13] vs - 1.93[- 1.84; - 0.42]%; p = 0.02). Different rapid-acting analogues provided similar results (HbA1c reduction vs MDI: - 0.25 [- 0.48; - 0.02]%, p = 0.03, and - 0.29 [- 0.49; - 0.09]%, p = 0.005, for
lispro and aspart, respectively). In addition, in trials comparing CSII with basal-bolus MDI, CSII reduced HbA1c to a similar extent irrespective of the use of either NPH or long-acting analogues as basal
insulin in the control groups (HbA1c reduction vs MDI: - 0.31 [- 0.55; - 0.06]%, p = 0.01, and - 0.20 [- 0.38; - 0.03]%, p = 0.02, for NPH and long-acting analogues, respectively. With respect to severe
hypoglycemia, CSII did not produce a significant reduction of risk in comparison with traditional
insulin injections. Conversely, CSII was associated with a significant increase in the incidence of reported
diabetic ketoacidosis (DKA). Notably, the increased risk of DKA was significant in trials comparing CSII with conventional
insulin therapy, whereas only a nonsignificant trend toward an increased risk was observed in comparisons with basal-bolus MDI. Only two trials comparing CSII with basal-bolus MDI, both using rapid-acting analogues, were performed on
insulin-naïve type 1 diabetic patients. When those two trials were analyzed separately, CSII did not produce any relevant effect on HbA1c (difference from control: - 0.10[- 0.38; + 0.17]%; p = 0.46). No meta-analysis could be performed on either severe
hypoglycemia or DKA, which were not reported by one of the two trials. CSII seems to produce a small improvement in HbA1c in patients with
type 1 diabetes inadequately controlled with MDI. This apparent effect, which could be partly due to publication bias, is smaller when MDI is properly performed using basal-bolus schemes with
short-acting insulin analogues. Other outcomes different from HbA1c (such as quality of life) could be relevant for the choice of CSII instead of MDI. In addition, further studies are needed to better define the profile of patients who could benefit most from CSII.