| Methods | Parallel randomised controlled trial, randomisation ratio 1:1, non‐inferiority design | |
| Participants |
Inclusion criteria: NIDDM, age = 35 to 70 years, insulin therapy for at least two months before study entry¹ Exclusion criteria: any other severe disease, current use of oral antidiabetic drugs or insulin infusion devices Diagnostic criteria: WHO 1980 |
|
| Interventions |
Number of study centres: multicentre (47 investigators) Treatment before study: human insulin therapy for at least 2 months before study Titration period: 12 months |
|
| Outcomes | Outcomes reported in abstract of publication: 1‐hr and 2‐hr postprandial rise in serum glucose, HbA1c | |
| Study details |
Run‐in period: 1 month² Study terminated early: no Trial register ID: not reported |
|
| Publication details |
Language of publication: English Funding: commercial (Eli Lilly) Publication status: full article in peer reviewed journal³ |
|
| Study aim for study | Quote from publication: "We examined the safety and efficacy of insulin lispro in the pre‐meal treatment of patients with diabetes mellitus" | |
| Notes | ¹Anderson 1997 combined two trials including type 1 and type 2 diabetic participants. The inclusion criteria listed here only refer to participants with type 2 diabetes ²According to IQWIG 2005, 2 to 4 weeks ³Anderson 1997 reports on the pooled results of trials Z012 1997 and Z014 1997; details on the individual trials were taken from IQWIG 2005 |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk |
Quote from publication: "Patients were then randomly assigned to receive either insulin lispro or regular human insulin as a pre‐meal injection" Comment: considered adequate in IQWIG 2005 |
| Allocation concealment (selection bias) | Low risk |
Quote from IQWiG report: "Allocation was done centrally" Comment: considered adequate in IQWIG 2005 |
| Blinding of participants and personnel (performance bias) All‐cause mortality | Low risk |
Quote from publication: "open‐label" Comment: outcome measure unlikely to be influenced by lack of blinding |
| Blinding of participants and personnel (performance bias) Severe hypoglycaemia | High risk |
Quote from publication: "open‐label" Comment: outcome measure likely influenced by lack of blinding |
| Blinding of participants and personnel (performance bias) HbA1c | Unclear risk | Quote from publication: "open‐label" |
| Blinding of participants and personnel (performance bias) Adverse events | High risk |
Quote from publication: "open‐label" Comment: outcome measure likely influenced by lack of blinding |
| Blinding of outcome assessment (detection bias) All‐cause mortality | Low risk |
Quote from publication: "open‐label" Comment: outcome measure unlikely influenced by lack of blinding |
| Blinding of outcome assessment (detection bias) Severe hypoglycaemia | High risk |
Quote from publication: "open‐label" Comment: outcome measure likely influenced by lack of blinding |
| Blinding of outcome assessment (detection bias) HbA1c | Low risk |
Quote from publication: "Blood samples were taken at 3‐month intervals for the determination of glycated haemoglobin (HbA1c) levels and analysed by a central laboratory" Comment: outcome measure unlikely to be influenced by lack of blinding |
| Blinding of outcome assessment (detection bias) Adverse events | High risk |
Quote from publication: "open‐label" Comment: outcome measure likely influenced by lack of blinding |
| Incomplete outcome data (attrition bias) All‐cause mortality | Low risk | Quote from IQWiG report: "Patients lost to follow‐up lispro N = 5 (6%); patients lost to follow‐up regular human insulin N = 6 (7%)" |
| Incomplete outcome data (attrition bias) Severe hypoglycaemia | Low risk | Quote from IQWiG report: "Patients lost to follow‐up lispro N = 5 (6%); patients lost to follow‐up regular human insulin N = 6 (7%)" |
| Incomplete outcome data (attrition bias) HbA1c | Low risk | Quote from IQWiG report: "Patients lost to follow‐up lispro n = 5 (6%); patients lost to follow up regular human insulin n = 6 (7%)" |
| Incomplete outcome data (attrition bias) Adverse events | Low risk | Quote from IQWiG report: "Patients lost to follow‐up lispro N = 5 (6%); patients lost to follow‐up regular human insulin N = 6 (7%)" |
| Selective reporting (reporting bias) | High risk | Comment: inconsistent information on primary outcomes in different study reports and publication |
| Other bias | High risk | Comment: primary outcome not clear; publication only provided results for pooled analyses of trials Z012 and Z014. The trial authors did not inform readers that these were results from pooled analyses |
Note: where the judgement is 'Unclear' and the description is blank, the trial did not report that particular outcome.
ADA: American Diabetes Association AE: adverse events BG: blood glucose BMI: body mass index CI: confidence interval DM: diabetes mellitus hr: hour(s) HbA1c: glycosylated haemoglobin A1c HR: human regular insulin HRQoL: health‐related quality of life IDDM: insulin‐dependent diabetes mellitus LP: insulin lispro NIDDM: non‐insulin‐dependent diabetes mellitus OAD: oral antidiabetic drug OGTT: oral glucose tolerance test ORBIT: Outcome Reporting Bias In Trials PG: plasma glucose RHI: regular human insulin T2DM: type 2 diabetes WHO: World Health Organization