SynthesisCardiovascular diabetology2021
SGLT2 inhibitors and lower limb complications: an updated meta-analysis.
Synthesis in Cardiovascular diabetology, 2021. The graph read 2 numbers from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. An erratum has been issued. Cited by 36 papers, 6 of them syntheses that pooled it.
What it found
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Read, but not usablea number the graph found but could not read as for or against
Compared with non-SGLT2i users, the risks of amputation and PAD were slightly increased in patients with canagliflozin treatment (amputation: OR = 1.60, 95% CI 1.04 to 2.46; PAD: OR = 1.53, 95 % CI 1.14 to 2.05).
Compared with non-SGLT2i users, the risks of amputation and PAD were slightly increased in patients with canagliflozin treatment (amputation: OR = 1.60, 95% CI 1.04 to 2.46; PAD: OR = 1.53, 95 % CI 1.14 to 2.05).
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Where it lands on the map
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What it adds to each cell
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SGLT2 inhibitors×cardiovascular events
No readable resultOpen on the map →What to test next →22 readable studies in this cell: 9 favour the treatment, 11 find no difference, 2 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.
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Who cites it
36 citing papers in PubMed, 6 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Intensive blood pressure reduction but an increased risk of peripheral arterial disease: a systematic review and meta-analysis of randomized controlled trials.Annals of medicine · 2025Pooled it
- Association between dipeptidyl peptidase-4 inhibitor use and diabetic retinopathy: a systematic review and meta-analysis of real-world studies.BMC ophthalmology · 2024Pooled it
- Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.BMJ (Clinical research ed.) · 2023Pooled it
- Neutral effects of SGLT2 inhibitors in acute coronary syndromes, peripheral arterial occlusive disease, or ischemic stroke: a meta-analysis of randomized controlled trials.Cardiovascular diabetology · 2023Pooled it
- Comparative safety of different recommended doses of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.Frontiers in endocrinology · 2023 · on this mapPooled it
- Comprehensive Analysis of Adverse Events Associated With SGLT2is: A Meta-Analysis Involving Nine Large Randomized Trials.Frontiers in endocrinology · 2021Pooled it
- Toxicological profile of anti-diabetic drugs and emerging measures to reduce the toxic burden.Toxicology reports · 2026Review
- Cardiovascular protection by SGLT2 inhibitors: an integrative review of mechanistic networks, clinical evidence, and safety considerations.Frontiers in cardiovascular medicine · 2026Review
- Differential Effect of GLP-1 Receptor Agonists and SGLT2 Inhibitors on Lower-Extremity Amputation Outcomes in Type 2 Diabetes: A Nationwide Retrospective Cohort Study.Diabetes care · 2025Article
- SGLT2 Inhibitors and GLP-1 Receptor Agonists in PAD: A State-of-the-Art Review.Journal of clinical medicine · 2025Review
- SGLT2 Inhibitors: From Structure-Effect Relationship to Pharmacological Response.International journal of molecular sciences · 2025Review
- Comparison of New-Onset Peripheral Artery Disease in Patients With Type 2 Diabetes Exposed to Sodium-Glucose Cotransporter-2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, or Glucagon-Like Peptide-1 Agonists: A Population-Based Cohort Study.Journal of the American Heart Association · 2025Article
- A Comprehensive Analysis of Diabetic Complications and Advances in Management Strategies.Journal of atherosclerosis and thrombosis · 2025Review
- Article
- Novel glucose-lowering agents that benefit diabetic foot: icing on the cake.Frontiers in endocrinology · 2025Review
- Effects of SGLT2 Inhibitors on Cardiovascular and Lower Limb Events in Patients with Type 2 Diabetes: A Nationwide Population-Based Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Unravelling the cardio-renal-metabolic-foot connection in people with diabetes-related foot ulceration: a narrative review.Cardiovascular diabetology · 2024Review
- The Potential Impact of SGLT2-I in Diabetic Foot Prevention: Promising Pathophysiologic Implications, State of the Art, and Future Perspectives-A Narrative Review.Medicina (Kaunas, Lithuania) · 2024Review
- The Role of Sodium-Glucose Cotransporter-2 Inhibitors in the Treatment Paradigm of CKD in Africa: An African Association of Nephrology Panel Position Paper.Kidney international reports · 2024Article
- Novel antidiabetic therapies in patients with peripheral artery disease: current perspective.Frontiers in clinical diabetes and healthcare · 2024Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
backgroundTo exam the associations between the use of sodium glucose co-transporter 2 inhibitor (SGLT2i) and the risk of lower limb complications, and to analyze the associated factors.
methodsPubmed, Medline, Embase, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from the inception to November 2020. Randomized controlled trials of SGLT2i conducted in population containing diabetic patients with reports of amputation, peripheral arterial disease (PAD) and diabetic foot (DF) events were included. Random-effect model, fixed-effect model and meta-regression analysis were accordingly used.
resultThe numbers of SGLT2i users versus non-SGLT2i users in the analyses of amputation, PAD and DF were 40,925/33,414, 36,446/28,685 and 31,907/25,570 respectively. Compared with non-SGLT2i users, the risks of amputation and PAD were slightly increased in patients with canagliflozin treatment (amputation: OR = 1.60, 95% CI 1.04 to 2.46; PAD: OR = 1.53, 95 % CI 1.14 to 2.05). Meta-regression analyses indicated that greater weight reduction in SGLT2i users was significantly associated with the increased risks of amputation (β = - 0.461, 95% CI - 0.726 to - 0.197), PAD (β = - 0.359, 95% CI - 0.545 to - 0.172) and DF (β = - 0.476, 95% CI - 0.836 to - 0.116). Lower baseline diastolic blood pressure (β = - 0.528, 95% CI - 0.852 to - 0.205), more systolic blood pressure reduction (β = - 0.207, 95% CI - 0.390 to - 0.023) and more diastolic blood pressure reduction (β = - 0.312, 95% CI - 0.610 to - 0.015) were significantly associated with the increased risks of amputation, PAD and DF respectively in patients with SGLT2i treatment.
conclusionsThe risks of amputation and PAD were slightly increased in patients with canagliflozin treatment. Reductions in body weight and blood pressure were associated with lower limb complications in patients with SGLT2i treatment.
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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 Socratic graph.