Barnett 2013.

Methods	Parallel randomised controlled clinical trial Randomisation ratio: 2:1 Equivalence design Controlled clinical trial (CCT): a Phase IIIb, extension of RCT
Participants	Inclusion criteria: Men and women aged 18–78 years with T2DM, fasting C‐peptide C 0.8 ng/mL, body mass index (BMI) B45 kg/m2, and inadequate glycaemic control (HbA1c 7.5%–11.0%) on a stable regimen of insulin (30–150 U/day, with B 20% variation in total daily dose for C 8 weeks before screening). Exclusion criteria: poorly controlled diabetes (e.g. marked polyuria and polydipsia with 10% weight loss during the 3 months before screening); history of diabetic ketoacidosis or hyperosmolar nonketotic coma; history of significant cardiovascular disease or haemoglobinopathy; contraindications to DPP‐4 inhibitors, metformin, or insulin; or pregnancy, breast feeding, or not using an acceptable method of birth control Diagnostic criteria: not stated
Interventions	Number of study centres: unclear Treatment before study: intermediate‐acting insulin, long‐acting (basal) insulin, or a premixed formulation in which rapid‐ or short‐acting insulin constituted one component was permitted. Participants could also be taking metformin if the daily dose was stable for C 8 weeks before screening. Titration period: 4 weeks
Outcomes	Primary outcome(s) (as stated in the publication): mean change from baseline to 52 weeks in HbA1c
Study details	Total study duration: 56 weeks Run‐in period: 4 weeks Study terminated early (for benefit/because of adverse events): no
Publication details	Language of publication: English Funding source: Bristol‐Myers‐Squibb and AstraZeneca Publication status: peer‐reviewed journal
Stated aim of study	To evaluate the safety and efficacy of the DPP4 inhibitor saxagliptin vs placebo as add‐on therapy in type 2 diabetes inadequately controlled with insulin with or without metformin
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from publication: "Patients were stratified based on metformin use at enrolment and randomised 2:1 via an interactive voice response system using a blocked randomisation schedule to receive saxagliptin 5 mg (Onglyza, Bristol‐Myers Squibb Company, Princeton, NJ, USA, and AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA) or placebo once daily as add‐on to baseline therapy with insulin or insulin plus metformin."
Allocation concealment (selection bias)	Low risk	Quote from publication: "To maintain blinding to patients and physicians, saxagliptin and placebo tablets were identical in appearance, and bottles were printed with a blinded label."
Blinding of participants and personnel (performance bias) Adverse events	Low risk	Quote from publication: "To maintain blinding to patients and physicians, saxagliptin and placebo tablets were identical in appearance, and bottles were printed with a blinded label."
Blinding of participants and personnel (performance bias) HbA1c, FPG, lipids	Low risk	Comment: FGP and lipids not assessed
Blinding of participants and personnel (performance bias) Insulin dose	Unclear risk	Quote from publication: "To maintain blinding to patients and physicians, saxagliptin and placebo tablets were identical in appearance, and bottles were printed with a blinded label."
Blinding of outcome assessment (detection bias) Adverse events	Unclear risk	Comment: unclear if the outcome assessor was blinded
Incomplete outcome data (attrition bias) Adverse events	High risk	Comment: no exact SDs are reported as text only in the figures
Incomplete outcome data (attrition bias) HbA1c, FPG, lipids	High risk	Comment: no exact SDs are reported as text only in the figures Comment: incomplete for FPG and lipids
Incomplete outcome data (attrition bias) Insulin dose	Low risk	Comment: available
Selective reporting (reporting bias)	High risk	Comment: no exact SDs are reported as text only in the figures
Other bias	Unclear risk	Comment: sponsoring by a pharmaceutical company