Table 1 Inclusion and exclusion criteria for SU add-on systematic review

Population

Adults (aged ≥18 years) with T2DM on a stable dose of a SU as monotherapy (for at least 8 weeks, at half the maximum dose or maximum tolerable dose) where SU alone, with diet and exercise, does not provide adequate glycaemic control.

Treatment pathway

Add-on pharmacological therapy after failure of SU monotherapy, where the first-line SU was initiated because metformin was considered inappropriate.

Interventions

Pharmacological therapies that would be added to a SU in clinical practice when SU monotherapy does not provide adequate glycaemic control.

Comparators

Active arms: Dual therapies of interest namely drugs/doses licensed in the EU, as a dual therapy in combination with a SU and as used in clinical practice[13].

Outcomes

To be included in the meta-analysis, studies needed to report at least 1 of the primary endpoints of interest at 24 +/- 6 weeks:

• mean change in HbA1c from baseline

• mean change in weight from baseline

• mean change in systolic blood pressure from baseline

• proportion (number) of patients experiencing at least 1 hypoglycaemia episode

Interim results from longer-term studies were permitted provided that dose titration and a sufficient maintenance period were complete at follow-up.

Study design

• Prospective, RCTs.

• If cross-over design then results reported prior to the cross-over period can be used in the meta-analysis.

• Minimum follow-up of 18 weeks to be included in the meta-analysis (i.e. 24 weeks +/-6 weeks); an expansion of the study window to 24 +/- 8 weeks as a sensitivity analysis for borderline studies was permitted.

Publications

Full-text publications, except for abstracts published in 2012 (for results from recently completed trials), full-text available in English.

Exclusions

• Results from uncontrolled open label extensions of RCTs.

• Studies of SU used as part of a triple therapy regimen.

• Study populations with moderate to severe renal impairment.

• Study arms using treatment dosing regimens that are not licensed in the EU.