Summary of findings for the main comparison. Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus.
| Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus | ||||||
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Patient or population: persons with type 1 diabetes mellitus Settings: outpatient clinics in North America and Europe Intervention: intensive glucose control Comparison: conventional glucose control | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | Intensive treatment | |||||
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Macrovascular complications Follow‐up: 1 ‐ 6.5 years |
See comment | ⊕⊕⊝⊝ lowa | Macrovascular outcomes were not considered as primary outcomes in any of the included studies and most studies did not report this outcome; myocardial infarctions and strokes were very rare | |||
| Microvascular complications | ||||||
| Manifestation of retinopathy Follow‐up: 5 ‐ 6.5 years | 232 per 1000 | 63 per 1000 (42 to 97) | RR 0.27 (0.18 to 0.42) | 768 (2) | ⊕⊕⊕⊕ highb | |
| Progression of retinopathy Follow‐up duration ≥ 2 years; follow‐up: 5 ‐ 6.5 years | 387 per 1000 | 236 per 1000 (190 to 294) | RR 0.61 (0.49 to 0.76) | 764 (2) | ⊕⊕⊕⊝ moderatec | |
| Progression of retinopathy Follow‐up duration < 2 years; follow‐up: 1 year | 149 per 1000 | 346 per 1000 (173 to 690) | RR 2.32 (1.16 to 4.63) | 96 (2) | ⊕⊕⊝⊝ lowd | |
| Manifestation of nephropathy Follow‐up: 3.5 ‐ 6.5 years | 284 per 1000 | 159 per 1000 (131 to 193) | RR 0.56 (0.46 to 0.68) | 1475 (3) | ⊕⊕⊕⊝ moderatee | |
| Progression of nephropathy Follow‐up: 5 ‐ 6.5 years | 14 per 1000 | 11 per 1000 (5 to 24) |
RR 0.79 (0.37 t0 1.70) |
179 (3) | ⊕⊝⊝⊝ very lowf | |
| Manifestation of neuropathy Follow‐up: 5 ‐ 6.5 years | 139 per 1000 | 49 per 1000 (32 to 74) | RR 0.35 (0.23 to 0.53) | 1203 (3) | ⊕⊕⊕⊕ highg | |
| Progression of neuropathy | See comment | Not adequately investigated | ||||
| Adverse events | ||||||
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Severe hypoglycaemia, baseline HbA1c < 9.0 Follow‐up: 1.5 ‐ 6.5 years |
351 per 1000 | 590 per 1000 (453 to 769) | RR 1.68 (1.29 to 2.19) | 1583 (3) | 1a. ⊕⊕⊝⊝ lowh | |
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Severe hypoglycaemia, baseline HbA1c ≥9.0 Follow‐up: 1 ‐ 5 years |
104 per 1000 | 108 per 1000 (68 to 170) | RR 1.04 (0.66 to 1.64) | 525 (8) | 1b. ⊕⊕⊝⊝ lowh | |
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Ketoacidosis Follow‐up: 1 ‐ 2 years |
21 per 1000 |
95 per 1000 (50 to 866) |
OR 4.93 (1.18 to 20.60) |
96 (3) | 2. ⊕⊝⊝⊝ very lowi | In studies using insulin pumps |
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Health‐related quality of life Follow‐up: 6.5 years |
See comment | 1441 (2) | ⊕⊕⊕⊝ moderatej | Only the DCCT reported on this outcome using several instruments (Diabetes‐Quality of Life Measure (DQHL), Symptom‐Checklist‐90R, Medical Outcome Study 36‐Item Short Form (SF‐36)); none of these measures showed a statistically significant difference between the intervention and comparator groups | ||
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All‐cause mortality Follow up: 1 ‐ 6.5 years |
14 per 1000 |
13 per 1000 (13 to 60) |
OR 1.02 (0.48 to 2.19) | 2039 (10) | ⊕⊕⊕⊝ moderatek | Overall, the mortality rate was very low in all studies except MDCCT 1994, investigating renal allograft as treatment for end‐stage diabetic nephropathy |
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Costs Follow up: 1 ‐ 6.5 years |
See comment | 1441 (2) | ⊕⊕⊕⊝ moderatej | Only the DCCT reported on this outcome; intensive treatment using multiple injections was calculated to cost 4014 US$/year, intensive treatment using CSII 5784 US$/year and conventional treatment 1666 US$/year taking into account resources used for therapy and handling side‐effects; considering the reduction of future diabetes complications, intensive therapy was found to be highly cost‐effective | ||
| **The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; CSII: continuous subcutaneous insulin infusion; DCCT: 'Diabetes Complications Clinical Trial'; HbA1c: glycosylated haemoglobin A1c; OR: odds ratio; RR: risk ratio | ||||||
| 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. | ||||||
The basis for the assumed risk is the number of events in the control groups
aDowngraded by two levels owing to outcome measures either not being addressed as primary endpoints or reported in included studies and few events bNot downgraded because of few participants due to large effect size (RR < 0.5) cDowngraded by one level owing to substantial diversity in outcome measures definition dDowngraded by two levels owing to few participants and substantial diversity in outcome measures definition eDowngraded by one level owing to indirectness (surrogate outcome measures) fDowngraded by three levels owing to few participants, indirectness (surrogate outcome measures) and imprecise results (confidence intervals include null effect and appreciable benefit or harm) gLarge effect size hDowngraded by two levels owing to risk of bias in outcome definition and observational nature of subgroup analyses iDowngraded by three levels owing to imprecision (wide confidence intervals), low number of participants and observational nature of subgroup analyses jDowngraded by one level because only one study group (DCCT) investigated this outcome in two studies kDowngraded by one level owing to imprecise results (confidence intervals include null effect and appreciable benefit or harm)