| Methods |
DURATION OF INTERVENTION:
52 weeks
DURATION OF FOLLOW‐UP:
52 weeks
RUN‐IN PERIOD:
none
LANGUAGE OF PUBLICATION:
English |
| Participants |
WHO PARTCIPATED:
mainly white patients with type 2 diabetes mellitus
INCLUSION CRITERIA:
age 35‐75 years, type 2 diabetes inadequately managed on sulphonylureas alone (at >=50% maximal recommended dosage or at maximal tolerated dose for >=3 months) and with stable or worsening glycaemic control for >=3 months; HbA1c 7.5‐11.0%, fasting C‐peptide >=1.5 ng/ml at screening; female patients post‐menopausal, sterilised or using adequate contraception
EXCLUSION CRITERIA:
type 1 diabetes or ketoacidosis; history of myocardial infarction, transient ischaemic attacks, or stroke in previous 6 months; symptomatic heart failure; malabsorption or pancreatitis; familial polyposis coli; malignant disease in previous 10 years; history of states associated with lactic acidosis or hypoxaemia; substance abuse; pregnant or breast‐feeding women; previous treatment with metformin, pioglitazone or other TZDs not permitted
DIAGNOSTIC CRITERIA:
not stated
CO‐MORBIDITIES:
not stated
CO‐MEDICATIONS:
thiazides allowed to treat oedema; if antihypertensive treatment indicated, ACE inhibitors, angiotensin II receptor antagonists or Ca antagonists used |
| Interventions |
NUMBER OF STUDY CENTRES:
multi, not stated
COUNTRY/ LOCATION:
various European countries, Canada
SETTING:
unclear
INTERVENTION (DOSE/DAY):
pioglitazone; up to 45 mg/day + sulphonylurea at pre‐study dose
CONTROL (DOSE/DAY):
metformin; 850 mg up to 3x/day (up to 2550 mg/day) + sulphonylurea at pre‐study dose
TREATMENT BEFORE STUDY:
‐ sulphonylurea at pre‐study level, no dose increases permitted; SU dose could only be downtitrated in case of symptomatic hypoglyceamia;
‐ most commonly used SUs in both groups: glibenclamide (42%);
gliclazide (31%); glimepiride (19%)
SU use from baseline to 52 weeks remained similar in both groups and there were very few cases of dose reduction.
TITRATION:
12 weeks forced titration:
‐ intervention 1: pioglitazone up to 45 mg/day with metformin placebo; starting with pioglitazone 15 mg/day; dose levels increased at weeks 4, 8, and 12 (maximal dose reached by 62%);
‐ control: metformin 850 mg with pioglitazone placebo up to three times a day (2550 mg/day); starting with metformin 850 mg/day; dose levels increased at weeks 4, 8, and 12 (55% reached maximal dose);
‐ cessation or down‐titration only allowed on basis of tolerability issues, including actual hypoglycaemia or increased risk of hypoglycaemia. Maximum tolerated dose established at week 12 maintained throughout remainder of study. |
| Outcomes |
PRIMARY OUTCOMES:
change in HbA1c from baseline to week 52
SECONDARY OUTCOMES:
FPG, insulin, C‐peptide, lipids, 32,33 split pro‐insulin, urinary albumine and creatinine, safety parameters, adverse events |
| Notes |
AIM OF STUDY:
to assess the 1 year efficacy and safety of the addition of pioglitazone or metformin to existing sulphonylurea therapy in patients with inadequately controlled type 2 diabetes |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Allocation concealment? |
Unclear risk |
B ‐ Unclear |
