SynthesisDiabetologia2016

Elevated serum magnesium associated with SGLT2 inhibitor use in type 2 diabetes patients: a meta-analysis of randomised controlled trials.

Huilin Tang, Xi Zhang, Jingjing Zhang, Yufeng Li, Liana C Del Gobbo, Suodi Zhai, Yiqing Song

Open access · bronzeAbstract readMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Diabetologia, 2016. The graph read 6 numbers from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. Cited by 73 papers, 1 of them a synthesis that pooled it.

6numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
8.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

Read, but not usablea number the graph found but could not read as for or against

Serum magnesium levelscanagliflozin 100 mg vs placebo, in patients without chronic kidney diseaseno interval or p-value · t2dfeeds one cell of the map
Δ 0.06
In patients without chronic kidney disease, each SGLT2 inhibitor significantly increased serum magnesium levels compared with placebo (canagliflozin: WMD 0.06 mmol/l for 100 mg and 0.09 mmol/l for 300 mg; dapagliflozin: WMD 0.1 mmol/l for 10 mg; empagliflozin: WMD 0.04 mmol/l for 10 mg and 0.07 mmol/l for 25 mg; and ipragliflozin: WMD 0.05 mmol/l for 50 mg).
Serum magnesium levelsdapagliflozin 10 mg vs placebo, in patients without chronic kidney diseaseno interval or p-value · t2dfeeds one cell of the map
Δ 0.10
In patients without chronic kidney disease, each SGLT2 inhibitor significantly increased serum magnesium levels compared with placebo (canagliflozin: WMD 0.06 mmol/l for 100 mg and 0.09 mmol/l for 300 mg; dapagliflozin: WMD 0.1 mmol/l for 10 mg; empagliflozin: WMD 0.04 mmol/l for 10 mg and 0.07 mmol/l for 25 mg; and ipragliflozin: WMD 0.05 mmol/l for 50 mg).
Serum magnesium levelsempagliflozin 10 mg vs placebo, in patients without chronic kidney diseaseno interval or p-value · t2dfeeds one cell of the map
Δ 0.04
In patients without chronic kidney disease, each SGLT2 inhibitor significantly increased serum magnesium levels compared with placebo (canagliflozin: WMD 0.06 mmol/l for 100 mg and 0.09 mmol/l for 300 mg; dapagliflozin: WMD 0.1 mmol/l for 10 mg; empagliflozin: WMD 0.04 mmol/l for 10 mg and 0.07 mmol/l for 25 mg; and ipragliflozin: WMD 0.05 mmol/l for 50 mg).
Serum magnesium levelsempagliflozin 25 mg vs placebo, in patients without chronic kidney diseaseno interval or p-value · t2dfeeds one cell of the map
Δ 0.07
In patients without chronic kidney disease, each SGLT2 inhibitor significantly increased serum magnesium levels compared with placebo (canagliflozin: WMD 0.06 mmol/l for 100 mg and 0.09 mmol/l for 300 mg; dapagliflozin: WMD 0.1 mmol/l for 10 mg; empagliflozin: WMD 0.04 mmol/l for 10 mg and 0.07 mmol/l for 25 mg; and ipragliflozin: WMD 0.05 mmol/l for 50 mg).
Serum magnesium levelsipragliflozin 50 mg vs placebo, in patients without chronic kidney diseaseno interval or p-value · t2dfeeds one cell of the map
Δ 0.05
In patients without chronic kidney disease, each SGLT2 inhibitor significantly increased serum magnesium levels compared with placebo (canagliflozin: WMD 0.06 mmol/l for 100 mg and 0.09 mmol/l for 300 mg; dapagliflozin: WMD 0.1 mmol/l for 10 mg; empagliflozin: WMD 0.04 mmol/l for 10 mg and 0.07 mmol/l for 25 mg; and ipragliflozin: WMD 0.05 mmol/l for 50 mg).
Serum magnesium levelscanagliflozin 300 mg vs placebo, in patients without chronic kidney diseaseno interval or p-value · t2dfeeds one cell of the map
Δ 0.09
In patients without chronic kidney disease, each SGLT2 inhibitor significantly increased serum magnesium levels compared with placebo (canagliflozin: WMD 0.06 mmol/l for 100 mg and 0.09 mmol/l for 300 mg; dapagliflozin: WMD 0.1 mmol/l for 10 mg; empagliflozin: WMD 0.04 mmol/l for 10 mg and 0.07 mmol/l for 25 mg; and ipragliflozin: WMD 0.05 mmol/l for 50 mg).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

SGLT2 inhibitors×kidney outcomes

No readable resultOpen on the map →What to test next →

13 readable studies in this cell: 10 favour the treatment, 1 find no difference, 2 favour the comparator.

Belief with this paper
0.89established · 8 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
1 · no effect
NCT02864914333,580 enrolled · 2016
IRR 0.690.45 to 1.05
NCT0546531762,197 enrolled · 2022
HR 0.750.65 to 0.86
NCT0173053417,190 enrolled · 2013
HR 0.760.67 to 0.87
NCT030579515,988 enrolled · 2017
Treatment by time interaction 1.360.86 to 1.86
NCT019897545,813 enrolled · 2014
HR 0.640.57 to 0.73
NCT020657914,401 enrolled · 2014
HR 0.700.59 to 0.82
NCT010326294,330 enrolled · 2009
OR 0.800.67 to 0.97
NCT030579773,730 enrolled · 2017
Treatment by time interaction 1.730.67 to 2.80

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Observational
  4. Article
  5. Article
  6. Review
  7. Article
  8. Magnesium Level and Related Factors in Type 2 Diabetes Mellitus: A Cross-Sectional StudyEndocrine, metabolic & immune disorders drug targets · 2026
    Article
  9. Article
  10. NovelKidney international reports · 2025
    Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Observational
  20. Observational

13 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Huilin TangDepartment of Pharmacy, Peking University Third Hospital, Beijing, People's Republic of China.
Xi ZhangDepartment of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, 1050 Wishard Blvd, Indianapolis, IN, 46202, USA.
Jingjing ZhangDivision of Nephrology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Yufeng LiDepartment of Endocrinology, Beijing Pinggu Hospital, Beijing, People's Republic of China.
Liana C Del GobboDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA.
Suodi ZhaiDepartment of Pharmacy, Peking University Third Hospital, Beijing, People's Republic of China.
Yiqing SongDepartment of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, 1050 Wishard Blvd, Indianapolis, IN, 46202, USA. yiqsong@iu.edu.
Indiana University – Purdue University Indianapolis · USPeking University · CNStanford University · USThomas Jefferson University · US

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

aims/hypothesisBy analysing available evidence from randomised controlled trials (RCTs), we aimed to examine whether and to what extent sodium-glucose cotransporter 2 (SGLT2) inhibitors affect serum electrolyte levels in type 2 diabetes patients.

methodsWe searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov up to 24 May 2016 for published RCTs of SGLT2 inhibitors that reported changes in serum electrolyte levels. Weighted mean differences (WMD) between each SGLT2 inhibitor and placebo were calculated using a random-effects model. Dose-dependent relationships for each SGLT2 inhibitor were evaluated using meta-regression analysis.

resultsEighteen eligible RCTs, including 15,309 patients and four SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin and ipragliflozin) were evaluated. In patients without chronic kidney disease, each SGLT2 inhibitor significantly increased serum magnesium levels compared with placebo (canagliflozin: WMD 0.06 mmol/l for 100 mg and 0.09 mmol/l for 300 mg; dapagliflozin: WMD 0.1 mmol/l for 10 mg; empagliflozin: WMD 0.04 mmol/l for 10 mg and 0.07 mmol/l for 25 mg; and ipragliflozin: WMD 0.05 mmol/l for 50 mg). Canagliflozin increased serum magnesium in a linear dose-dependent manner (p = 0.10). Serum phosphate was significantly increased by dapagliflozin. Serum sodium appeared to significantly differ by SGLT2 inhibitor type. No significant changes in serum calcium and potassium were observed. Findings were robust after including trials involving patients with chronic kidney disease. CONCLUSIONS/

interpretationSGLT2 inhibitors marginally increased serum magnesium levels in type 2 diabetes patients indicating a drug class effect. Further investigations are required to examine the clinical significance of elevated magnesium levels in individuals with type 2 diabetes.

Indexed as

Sodium-Glucose Transporter 2 InhibitorsBenzhydryl CompoundsCanagliflozinDiabetes Mellitus, Type 2FemaleGlucosidesHumansMagnesiumMaleRandomized Controlled Trials as TopicThiophenesBenzhydryl CompoundsCanagliflozindapagliflozinempagliflozinGlucosidesipragliflozinMagnesiumSodium-Glucose Transporter 2 InhibitorsThiophenesMeta-analysisSerum electrolytesSerum magnesiumSGLT2 inhibitorsType 2 diabetes

Identifiers

PMID27628105
OpenAlexW2418869077

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.