Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and microvascular outcomes in patients with type 2 diabetes: systematic review and meta-analysis

Dorsey-Treviño, Edgar Gerardo; González-González, José Gerardo; Alvarez‐Villalobos, Neri Alejandro; González-Nava, Victoria; Contreras-Garza, B. M.; González-Colmenero, Alejandro Díaz; Rodríguez-Tamez, Giselle; Barrera, Francisco J.; Farrell, Ann; Montori, Víctor M.; Rodríguez-Gutiérrez, René

doi:10.1007/s40618-019-01103-9

Cited by 30 publications

(32 citation statements)

References 76 publications

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“…Our findings bear similarities and differences to other meta-analysis on this topic. In additional to the previously referenced meta-analysis [10], two recent meta-analyses of RCTs published in May and September 2019, respectively, found a non-significant increased risk of amputation among three large studies assessing canagliflozin, dapagliflozin, and empagliflozin [45] [46]. The overall finding of non-significance in these studies mirrors our own, while in contrast, we were able to meta-analyze the results for three individual products, and our findings were also supplemented by the inclusion of observational studies that similarly were inconclusive in aggregate but also were suggestive an elevated risk for canagliflozin.…”

Section: Plos Onementioning

confidence: 85%

Association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and lower extremity amputation: A systematic review and meta-analysis

et al. 2020

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Background The association between sodium-glucose cotransporter 2 inhibitors (SGLT2i's) and lower extremity amputation is unclear. Purpose To systematically review randomized control trials (RCTs) and observational studies quantifying risk of lower extremity amputations associated with SGLT2i use. Data sources and study selection We searched PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from January 2011 to February 2020 for RCTs and observational studies including lower extremity amputation outcomes for individuals with type 2 diabetes mellitus treated with SGLT2i's vs. alternative treatments or placebo. Data extraction and synthesis Two reviewers independently extracted data. Main outcomes and measures Our primary outcome was risk of lower limb amputation. Secondary outcomes included peripheral arterial disease, peripheral vascular disease, venous ulcerations, and diabetic foot infections. We also evaluated the risk of bias. We conducted random and fixed effects relative risk meta-analysis of RCTs.

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Section: Plos Onementioning

confidence: 85%

Association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and lower extremity amputation: A systematic review and meta-analysis

et al. 2020

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“…The GRADE instrument was used by seven reviews 17‐23 . For the main comparisons, we performed quality assessments of the evidence for the remaining reviews.…”

Section: Resultsmentioning

confidence: 99%

Sodium‐glucose cotransporter‐2 inhibitors for type 2 diabetes mellitus in adults: An overview of 46 systematic reviews

Augusto

Cassola

Dualib

et al. 2021

Diabetes Obesity Metabolism

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Aims To summarize the evidence from systematic reviews (SRs) of randomized controlled trials (RCTs) evaluating the efficacy and safety of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors versus placebo or active comparators for type 2 diabetes mellitus. Materials and Methods We searched six databases between 2014 and 2021. We assessed the quality of evidence using Assessment of Multiple Systematic Reviews (AMSTAR 2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) and summarized the main outcome results according to their evidence of benefit (PROSPERO ID: CRD42019132431). Results We included 46 SRs, comprising 175 RCTs and 136 096 participants. The results showed “clear evidence of benefit” in relation to: myocardial infarction (odds ratio [OR]/hazard ratio [HR] 0.85 to 0.91); cardiovascular mortality (OR/HR 0.67 to 0.86); heart failure (OR/HR 0.64 to 0.69); albuminuria progression and composite renal outcome (relative risk [RR]/HR 0.55 to 0.63); glycated haemoglobin (HbA1c) versus placebo (mean difference [MD] −0.49% to −0.77% [5.4 to 8.4 mmol/mol]); and weight versus placebo (MD −1.09 kg to −2.99 kg). “Possible benefit” was observed in relation to major adverse cardiovascular events (OR/HR 0.80 to 0.89), all‐cause mortality and nonalcoholic fatty liver disease. SGLT2 inhibitors showed “clear evidence of no effect or equivalence” in relation to stroke and fractures. “Clear evidence of harm” was observed in relation to genital infections (RR/OR 2.06 to 5.25) and ketoacidosis (HR/OR 1.36 to 2.20). Regarding amputation risk and urinary tract infections, we found “no conclusions possible due to lack of evidence”. Conclusions Our results showed that SGLT2 inhibitors have beneficial effects in relation to renal and cardiovascular outcomes (except for stroke), HbA1c and weight. Further studies are needed to assess urinary infections and amputation risk.

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“…However, there have been few studies discussing the treatment effects of SGLT2 inhibitors on DMO. Meta‐analyses from randomized controlled trials have indicated that SGLT2 inhibitors did not have adverse effects on ocular outcomes, 18‐21 and only some case reports have suggested SGLT2 inhibitors improve or resolve DMO 22,23 …”

Section: Introductionmentioning

confidence: 99%

Risk of diabetic macular oedema with sodium‐glucose cotransporter‐2 inhibitors in type 2 diabetes patients: A multi‐institutional cohort study in Taiwan

Shao

Lai

et al. 2021

Diabetes Obesity Metabolism

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Aims To investigate the risk of diabetic macular oedema (DMO) associated with the use of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM). Materials and Methods We conducted a retrospective cohort study by analysing a large multi‐institutional electronic medical records database in Taiwan. We included adult patients with T2DM without DMO newly receiving either SGLT2 inhibitors or glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) during the period 2016 to 2018. We used propensity scores with inverse probability of treatment weighting to generate comparable groups. The study outcome was incident DMO, determined by clinical diagnosis during outpatient visits or admissions. We followed patients from the index date to either DMO occurrence, last clinical visit, patient death, or December 31, 2020. We performed Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of DMO. Results We included 9986 new users of SGLT2 inhibitors (mean [SD] age 59.6 (12.1) years, median [interquartile range {IQR}] glycated haemoglobin [HbA1c] 70 (61‐81)mmol/mol, estimated glomerular filtration rate [eGFR] 89.1 [71.4‐108.7] mL/min/1.73 m2 and urine albumin‐creatinine ratio [UACR] 26.1 [9.7‐117.6] mg/g) and 1067 new users of GLP‐1RAs (mean [SD] age 58.4 (41.5) years, median [IQR] HbA1c 73 [64‐84] mmol/mol, eGFR 91.6 [68.6‐114.0] mL/min/1.73 m2 and UACR 37.6 [11.1‐153.2] mg/g) with similar baseline characteristics. Lower DMO risks were observed among patients newly receiving SGLT2 inhibitors (7.9/1000 person‐years), compared to those receiving GLP‐1RAs (10.7/1000 person‐years) with an HR of 0.75 (95% CI 0.64‐0.88). Conclusions Our findings suggest use of SGLT2 inhibitors was associated with lower risk of DMO in T2DM patients in clinical practice, compared to use of GLP‐1RAs. Future studies are necessary to confirm this observation.

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Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and microvascular outcomes in patients with type 2 diabetes: systematic review and meta-analysis

Cited by 30 publications

References 76 publications

Association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and lower extremity amputation: A systematic review and meta-analysis

Association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and lower extremity amputation: A systematic review and meta-analysis

Sodium‐glucose cotransporter‐2 inhibitors for type 2 diabetes mellitus in adults: An overview of 46 systematic reviews

Risk of diabetic macular oedema with sodium‐glucose cotransporter‐2 inhibitors in type 2 diabetes patients: A multi‐institutional cohort study in Taiwan

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