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. 2016 Nov;82(5):1291-1302.
doi: 10.1111/bcp.13059. Epub 2016 Aug 3.

Hypoglycaemia when adding sulphonylurea to metformin: a systematic review and network meta-analysis

Stig Ejdrup Andersen  1 , Mikkel Christensen  2
Affiliations

Hypoglycaemia when adding sulphonylurea to metformin: a systematic review and network meta-analysis

Stig Ejdrup Andersen et al. Br J Clin Pharmacol. 2016 Nov.

Abstract

Aims: The risk of hypoglycaemia may differ among sulphonylureas (SUs), but evidence from head-to-head comparisons is sparse. Performing a network meta-analysis to use indirect evidence from randomized controlled trials (RCTs), we compared the relative risk of hypoglycaemia with newer generation SUs when added to metformin.

Methods: A systematic review identified RCTs lasting 12-52 weeks and evaluating SUs added to inadequate metformin monotherapy (≥1000 mg/day) in type 2 diabetes. Adding RCTs investigating the active comparators from the identified SU trials, we established a coherent network. Hypoglycaemia of any severity was the primary end point.

Results: Thirteen trials of SUs and 14 of oral non-SU antihyperglycaemic agents (16 260 patients) were included. All reported hypoglycaemia only as adverse events. Producing comparable reductions in HbA1C of -0.66 to -0.84% (-7 to -9 mmol/mol), the risk of hypoglycaemia was lowest with gliclazide compared to glipizide (OR 0.22, CrI: 0.05 to 0.96), glimepiride (OR 0.40, CrI: 0.13 to 1.27), and glibenclamide (OR 0.21, CrI: 0.03 to 1.48). A major limitation is varying definitions of hypoglycaemia across studies.

Conclusions: When added to metformin, gliclazide was associated with the lowest risk of hypoglycaemia between the newer generation SUs. Clinicians should consider the risk of hypoglycaemia agent-specific when selecting an SU agent.

Keywords: hypoglycaemia; network meta-analysis; oral antiglycaemic agents; relative safety; sulphonylurea; type 2 diabetes.

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Figures

Figure 1
Figure 1
PRISMA flow chart of study selection results
Figure 2
Figure 2
The evidence network of eligible comparisons for hypoglycaemia. The width of the lines is proportional to the number of trials comparing each pair of treatments, and the area of each node is proportional to the number of randomized participants (sample size)
Figure 3
Figure 3
The cumulative rankogram of the estimated probability that, given the priors and the data, each SU agent has the lowest rate of hypoglycaemia (rank 1), the second lowest (rank 2), etc., among the compared agents
Figure 4
Figure 4
Comparative risk of hypoglycaemia (A) and comparative effect on HgbA1c (B) and body weight (C) when comparing the individual oral anti‐glycaemic agents + metformin using metformin + placebo as reference. Results with 95% credibility intervals (CI) are: (A) odds ratios (ORs); (B) absolute difference (%); and (C) absolute difference (kg)
See this image and copyright information in PMC

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