SynthesisOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2020
Association between combined treatment with SGLT2 inhibitors and metformin for type 2 diabetes mellitus on fracture risk: a meta-analysis of randomized controlled trials.
Synthesis in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2020. The graph read 1 number from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 13 papers, 4 of them syntheses that pooled 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
SGLT2is combined with metformin use did not influence fracture risk compared with metformin monotherapy or other comparators in patients with T2DM (OR = 0.97, 95% CI 0.71-1.32).
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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.
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.
Metformin×adverse events & safety
No readable resultOpen on the map →What to test next →22 readable studies in this cell: 9 favour the treatment, 8 find no difference, 5 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
SGLT2 inhibitors×adverse events & safety
No readable resultOpen on the map →What to test next →38 readable studies in this cell: 18 favour the treatment, 19 find no difference, 1 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
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.
Who cites it
13 citing papers in PubMed, 4 syntheses or guidelines pooled it, 19 citations in OpenAlex.
- Risk of bone fracture by using dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus: a network meta-analysis of population-based cohort studies.Frontiers in endocrinology · 2024Pooled it
- [Diagnosis and management of patients with diabetes and co-existing osteoporosis (Update 2023) : Common guideline of the Austrian Society for Bone and Mineral Research and the Austrian Diabetes Society].Wiener klinische Wochenschrift · 2023Guideline
- Association of metformin use with fracture risk in type 2 diabetes: A systematic review and meta-analysis of observational studies.Frontiers in endocrinology · 2022 · on this mapPooled it
- Pooled it
- Management of type 2 diabetes, 2026. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetologia · 2026Article
- Metformin as a Metabolic Reprogramming Interface in Host-Pathogen and Bone Microenvironment Crosstalk: A Dual-Target Strategy Against Antimicrobial Resistance and Osteoporotic Bone Loss.Antibiotics (Basel, Switzerland) · 2026Review
- SGLT2 inhibitors as metabolic modulators: beyond glycemic control in type 2 diabetes.Frontiers in endocrinology · 2025Review
- Hypoglycemic agents and bone health; an umbrella systematic review of the clinical trials' meta-analysis studies.Diabetology & metabolic syndrome · 2024Review
- Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetologia · 2022 · on this mapReview
- Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetes care · 2022 · on this mapReview
- Fracture Risk of Sodium-Glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease.Clinical journal of the American Society of Nephrology : CJASN · 2022Article
- Sodium-glucose cotransporter 2 inhibitors do not increase the risk of fractures in real-world clinical practice in Korea: A national observational cohort study.Journal of diabetes investigation · 2022Observational
- Comparison of the effect of Dapagliflozin and Pioglitazone on the risk of osteoporosis in postmenopausal women with Type-2 diabetes.Pakistan journal of medical sciencesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The marked sentences are the ones the graph read a number from.
This study analyzed the effects of combination therapy with sodium-glucose transporter-2 inhibitors (SGLT2is) and metformin on fracture risk. Summarizing available randomized controlled trials, we found that SGLT2is combined with metformin therapy did not influence fracture risk compared with metformin monotherapy or other comparators in patients with T2DM.
introductionNo study is available evaluating the association between sodium-glucose transporter-2 inhibitors (SGLT2is) in combination with metformin use and fracture risk. Our study aimed to investigate the fracture risk of combination therapy with SGLT2is and metformin in patients with type 2 diabetes mellitus (T2DM).
methodsPubMed, Embase, ClinicalTrials.gov site, and the Cochrane Library databases were scrutinized for all eligible randomized controlled trials (RCTs). The summarized odds ratios (ORs) and their 95% confidence intervals (CI) were calculated using Review Manager 5.3 software.
resultsA total of 25 RCTs involving 19,500 participants with T2DM were included in our studies. There were 88 fracture cases in the SGLT2is in combination with metformin therapy group and 79 in the control group. SGLT2is combined with metformin use did not influence fracture risk compared with metformin monotherapy or other comparators in patients with T2DM (OR = 0.97, 95% CI 0.71-1.32). After stratification by drug type, follow-up time, control regimen, and type of fracture, the upshots were still stable.
conclusionSGLT2is and metformin combination therapy did not influence fracture risk compared with metformin monotherapy or other comparators in patients with T2DM. PROSPERO REGISTRATION NUMBER: CRD42020168435.
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Registered trials
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 OpenQuestion graph.