Summary of findings 3. Summary of findings: pioglitazone.

Combinations of insulin and pioglitazone compared with insulin monotherapy for diabetes mellitus
Patient: participants with type 2 diabetes mellitus Settings: mostly secondary care outpatients and clinical research centre Intervention: pioglitazone plus insulin Comparison: insulin monotherapy
Outcomes	Insulin monotherapy	Insulin plus pioglitazone	No of participants (studies)	Quality of the evidence (GRADE)	Comments
All‐cause mortality	See comment	See comment	See comment	See comment	Not investigated
Diabetes‐related mortality	See comment	See comment	See comment	See comment	Not investigated
Diabetes‐related morbidity	See comment	See comment	See comment	See comment	Not investigated
Health‐related quality of life	See comment	See comment	See comment	See comment	Not investigated
Patient satisfaction	See comment	See comment	See comment	See comment	Not investigated
Adverse events: a. mild to moderate hypoglycaemia (episodes per participant) Follow‐up: 16 weeks to 6 months b. weight gain (kg) Follow‐up: 16 weeks to 6 months c. oedema (%) Follow‐up: 16 weeks to 6 months	a. range 9‐75 b. the mean weight gain across control groups ranged from 0.2 kg to 1.7 kg c. range 4%‐7%	a. range 15‐90 b. the mean weight gain in the intervention groups was3.8 kg higher (3.0 kg higher to 4.6 kg higher) c. range 16%‐18%	a. 760 (2) b. 288 (2) c. 760 (2)	a. ⊕⊕⊝⊝ lowa b. ⊕⊕⊝⊝ lowb c. ⊕⊕⊝⊝ lowb	a. the proportion of all hypoglycaemic episodes was higher in the pioglitazone‐insulin combination group compared to insulin monotherapy; serious hypoglycaemic episodes were rare b. the minimum of 1.9 kg weight gain is clinically relevant, because it may have been partially caused by oedema c. pioglitazone was associated with a higher frequency of oedema which increased with dose. In addition, Rosenstock 2002 reported congestive heart failure for two participants receiving 15 mg pioglitazone and two participants receiving 30 mg pioglitazone.
HbA1c, change from baseline (%) Follow‐up: 12 weeks to 6 months	See comment	See comment	785 (3)	⊕⊕⊝⊝ lowc	The mean difference in HbA1c for insulin‐pioglitazone combination therapy ranged from ‐0.5% to ‐1.0% and for insulin monotherapy from ‐0.6% to 0%
CI: confidence interval; HbA1c: glycosylated haemoglobin A1c
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

^aDowngraded by two levels because of risk of performance bias, indirectness and imprecision
 ^bDowngraded by two levels because of unclear risk of bias in several risk of bias domains, indirectness and imprecision
 ^cDowngraded by two levels because of unclear risk of bias in several risk of bias domains, indirectness and imprecision