Descriptive only
Acute kidney injury
Type 2 diabetes (adults)
longest follow-upRecorded harmsDoses of a drug pooledHazard ratio (from event counts)
15
Randomized trials
14
Treatments
6,916
Participants
17
Events
In plain language
No network meta-analysis was fitted here. The protocol requires at least two trials forming a connected network; this outcome has 15 trials. The trial data below are shown as reported.
Network of trials
Each circle is a treatment; each line joins treatments that were randomized against each other in at least one trial.
Comparability of the trials
Checked across designs (the set of treatments each trial compares) for eligibility, outcome definition and assessment, and the baseline factors above. Flags point to possible intransitivity; notes describe variation that is not tied to design.
- NoteOutcome assessment, time point: selected time points span 0.43 to 62 weeks
- NoteOutcome assessment, analysis set: mixed: full_analysis 1, randomized 1, safety 13
- NoteOutcome assessment, definition: mixed: EAC confirmed acute kidney injury 1, hypoglycemia requiring medical assistance 1, level 3 severe hypoglycemia 1, minor: symptomatic, glucose below 3.0 mmol/L, not major 1, not stated 11
- NoteOutcome assessment, adjudicated: mixed: not stated 11, yes 4
- NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 14, while_on_treatment 1
- NoteOutcome assessment, intercurrent events (rescue): mixed: not stated 14, treatment_policy 1
- NoteRisk of bias, blinding: mixed: double_blind 12, open_label 2, single_blind 1
- NoteRisk of bias, funding: mixed: industry 13, non_industry 2
- NoteData handling, input conversions: arms_combined 11, nonserious_only 9, printed_denominator 2
| Trial | definition | time weeks | analysis set | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AMPLITUDE-M | not stated | 62 | safety | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | type 2 diabetes on diet and exercise, HbA1c 7 to 10 percent, no glucose lowering drug in prior 3 months |
| NCT04466904 | not stated | 20 | safety | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2020 | age 18 to 75; T2D on diet and exercise or stable metformin; HbA1c 7.5 to 11.0 percent; BMI 20 to 35 |
| PIONEER 4 | not stated | 57 | safety | not stated | yes | not stated | not stated | not stated | double_blind | industry | 2016 | Age 18 or older; T2D on metformin with or without SGLT2i; HbA1c 7.0 to 9.5 percent; eGFR 60 or more |
| PIONEER 10 | not stated | 57 | safety | not stated | yes | not stated | while_on_treatment | treatment_policy | single_blind | industry | 2017 | Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug |
| NCT00765817 | not stated | 30 | full_analysis | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2008 | adults 18 or older; insulin glargine 20 U/d or more alone or with metformin or pioglitazone; HbA1c 7.1 to 10.5 percent; BMI 45 or less |
| NCT05579977 | not stated | 28 | safety | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2022 | age 18 to 75; T2D cohort on metformin, HbA1c 7.0 to 10.0, BMI 23 or more; obesity cohort BMI 30 or more without diabetes |
| PIONEER 12 | EAC confirmed acute kidney injury | 31 | safety | not stated | yes | not stated | not stated | not stated | double_blind | industry | 2019 | adults with type 2 diabetes on metformin, HbA1c 7.0 to 10.5 percent |
| NCT02229383 | minor: symptomatic, glucose below 3.0 mmol/L, not major | 38 | safety | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2014 | adults; insulin glargine 20 U/d or more with or without metformin; HbA1c 7.0 to 10.5 percent at randomization |
| ACHIEVE-5 | not stated | 42 | safety | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2023 | adults with T2D on insulin glargine with or without metformin or SGLT2 inhibitor |
| SOLID-DKD | level 3 severe hypoglycemia | 18 | safety | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2024 | age 18 to 75; T2D with UACR 300 to below 3000 mg/g; eGFR 30 or more; HbA1c 6.5 to 10; BMI 20 to 40 |
| NCT05486065 | not stated | 49 | safety | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2022 | age 18 to 64; HbA1c 7.0 to 10.5; BMI 27 or more; on metformin |
| PIONEER 11 | not stated | 31 | safety | not stated | yes | not stated | not stated | not stated | double_blind | industry | 2019 | age 18 or older; HbA1c 7.0 to 10.0 percent at screening, 7.0 to 9.5 at randomization; no glucose lowering drugs; eGFR 60 or more |
| AGAC2 | not stated | 0.43 | randomized | not stated | not stated | not stated | not stated | not stated | open_label | non_industry | 2011 | age over 20, T2DM over 2 years, A1C 8 to 12 percent, premixed insulin twice daily over 0.6 U/kg/day |
| ACHIEVE-1 | not stated | 42 | safety | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2023 | adults with type 2 diabetes on diet and exercise alone; HbA1c 7.0 to 9.5 percent |
| S003079 | hypoglycemia requiring medical assistance | 5 | safety | not stated | not stated | not stated | not stated | not stated | open_label | non_industry | 2010 | age 18 to 80, HbA1c 7.5 to 12 percent, BMI 21 to 35, T2D at least 6 months |
Trial data
What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the hazard ratio (from event counts) on the analysis scale (log) against the trial's first row. Flags mark converted, combined or approximated inputs.
| Trial | Arm | Treatment | Week | Data | Value | SE | Events / N | Flags | Source |
|---|---|---|---|---|---|---|---|---|---|
| PIONEER 4 | A1 | SEMA_PO | 57 | arm, events | 0 / 285 | R0015836:Supplement Table S8 | |||
| PIONEER 4 | A2 | LIRA_SC | 57 | arm, events | 1 / 284 | R0015836:Supplement Table S8 | |||
| PIONEER 4 | A3 | PLACEBO | 57 | arm, events | 0 / 142 | R0015836:Supplement Table S8 | |||
| PIONEER 10 | A1+A2+A3 | SEMA_PO | 57 | arm, events | 0 / 393 | arms_combined | R0018421:Table 2 | ||
| PIONEER 10 | A4 | DULA_SC | 57 | arm, events | 0 / 65 | R0018421:Table 2 | |||
| NCT00765817 | A1 | EXEN_SC | 30 | arm, events | 0 / 138 | R0027069:Results | |||
| NCT00765817 | A2 | PLACEBO | 30 | arm, events | 0 / 123 | R0027069:Results | |||
| NCT05579977 | A1+A8 | PLACEBO | 28 | arm, events | 0 / 139 | nonserious_only;arms_combined | registry:adverse_events | ||
| NCT05579977 | A10+A11+A12+A13+A2+A3+A4+A5+A6+A9 | LOTI_PO | 28 | arm, events | 3 / 690 | nonserious_only;arms_combined | registry:adverse_events | ||
| NCT05579977 | A7 | SEMA_PO | 28 | arm, events | 0 / 73 | nonserious_only | registry:adverse_events | ||
| PIONEER 12 | A1+A2+A3 | SEMA_PO | 31 | arm, events | 3 / 1,082 | arms_combined | R0019776:ESM Table 4 | ||
| PIONEER 12 | A4 | SITAGLIPTIN | 31 | arm, events | 1 / 359 | R0019776:ESM Table 4 | |||
| NCT02229383 | A1 | EXENER_SC | 38 | arm, events | 1 / 233 | R0014763:Table 3 | |||
| NCT02229383 | A2 | PLACEBO | 38 | arm, events | 0 / 231 | R0014763:Table 3 | |||
| ACHIEVE-5 | A1 | PLACEBO | 42 | arm, events | 0 / 141 | nonserious_only | registry:adverse_events | ||
| ACHIEVE-5 | A2+A3+A4 | ORFO_PO | 42 | arm, events | 1 / 405 | nonserious_only;arms_combined | registry:adverse_events | ||
| SOLID-DKD | A1+A2 | HRS7535_PO | 18 | arm, events | 1 / 187 | arms_combined | R0004355:Table 2 | ||
| SOLID-DKD | A3 | PLACEBO | 18 | arm, events | 1 / 94 | R0004355:Table 2 | |||
| NCT05486065 | A1+A2+A3 | SEMA_SC | 49 | arm, events | 0 / 185 | arms_combined | R0005510:Table 2 | ||
| NCT05486065 | A4 | PLACEBO | 49 | arm, events | 1 / 60 | R0005510:Table 2 | |||
| PIONEER 11 | A1+A2+A3 | SEMA_PO | 31 | arm, events | 1 / 390 | arms_combined | R0019663:Supplement Table 6 | ||
| PIONEER 11 | A4 | PLACEBO | 31 | arm, events | 0 / 131 | R0019663:Supplement Table 6 | |||
| AGAC2 | A1 | PLACEBO | 0.43 | arm, events | 0 / 21 | R0020827:Results | |||
| AGAC2 | A2 | EXEN_SC | 0.43 | arm, events | 0 / 30 | R0020827:Results | |||
| ACHIEVE-1 | A1 | PLACEBO | 42 | arm, events | 0 / 138 | nonserious_only | registry:adverse_events | ||
| ACHIEVE-1 | A2+A3+A4 | ORFO_PO | 42 | arm, events | 2 / 421 | nonserious_only;arms_combined | registry:adverse_events | ||
| AMPLITUDE-M | A1+A2+A3 | EFPE_SC | 62 | arm, events | 1 / 304 | nonserious_only;arms_combined | registry:adverse_events | ||
| AMPLITUDE-M | A4 | PLACEBO | 62 | arm, events | 0 / 102 | nonserious_only | registry:adverse_events | ||
| NCT04466904 | A1+A2 | MAZD_SC | 20 | arm, events | 0 / 16 | arms_combined | R0009340:Supplement Table S3 | ||
| NCT04466904 | A4 | DULA_SC | 20 | arm, events | 0 / 6 | printed_denominator | R0009340:Supplement Table S3 | ||
| NCT04466904 | A5 | PLACEBO | 20 | arm, events | 0 / 12 | printed_denominator | R0009340:Supplement Table S3 | ||
| S003079 | A1 | EXEN_SC | 5 | arm, events | 0 / 18 | R0025923:Results | |||
| S003079 | A2 | STANDARD_CARE | 5 | arm, events | 0 / 18 | R0025923:Results |
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