Adverse events associated with sodium glucose co-transporter 2 inhibitors: an overview of quantitative systematic reviews

Pelletier, Ryan; Ng, Kelvin; Alkabbani, Wajd; Labib, Youssef; Mourad, Nicolas; Gamble, John‐Michael

doi:10.1177/2042098621989134

Cited by 55 publications

(52 citation statements)

References 65 publications

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“…Taken together, the rationale for co‐administration of pioglitazone and canagliflozin (or other SGLT‐2 inhibitors in general), particularly in the early stage of T2DM similar to the subjects in this study, is scientifically sound with respect to the pathophysiological background of T2DM such as increased insulin resistance/decreased beta‐cell function and a broad range of metabolic abnormalities including lipids. Both these drugs are known to possess CV protection, though certain adverse events could be a concern as described in Introduction 1‐7 . Nevertheless, if CV risks are reduced with these drugs, this might outweigh the risk of such adverse events.…”

Section: Discussionmentioning

confidence: 99%

Complementary effects on glycaemic and non‐glycaemic parameters between responders and non‐responders treated with pioglitazone and canagliflozin in drug‐naive subjects with type 2 diabetes

Kutoh¹,

Kuto²,

Wada³

et al. 2021

Int J Clinical Practice

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Objectives The aim of this study was to investigate the differential regulation of metabolic parameters between pioglitazone and canagliflozin in relation to their glycaemic efficacies. Methods Drug‐naive subjects with T2DM received pioglitazone 15‐30 mg/day or canagliflozin 50‐100 mg/day monotherapy for 3 months. Those who had a ≥1% reduction in HbA1c were defined as responders and others who had a <1% reduction were defined as non‐responders. Results In the pioglitazone group, baseline BMI, FFA, HOMA‐R or adipo‐IR was significantly higher, and HDL‐C was significantly lower in responders vs non‐responders. In the canagliflozin group, baseline HbA1c or FBG was significantly higher, and HOMA‐B or age was significantly lower in responders vs non‐responders. In pioglitazone responders, significant decreases in HbA1c (from 10.75% to 8.31%), FBG (−29.7%), FFA (−37.7%), non‐HDL‐C (−13.4%), TG (−30.1%), HOMA‐R (−35.6%) or adipo‐IR (−38.7%), and increases in BMI (2.8%) or HDL‐C (14.2%) were observed. In pioglitazone non‐responders, none of the parameters were regulated. In canagliflozin responders, significant decreases in HbA1c (from 11.31% to 8.60%), FBG (32.1%), BMI (−2%) or HOMA‐R (−33.8%), and increases in HOMA‐B (50%) were observed. In canagliflozin non‐responders, significant decreases in BMI (−2.4%), insulin (−21.8%) or HOMA‐R (−33.6%) were observed. Conclusions (i) Glycaemic efficacy of pioglitazone is linked to body weight and atherogenic lipids while this is not the case with canagliflozin. (ii) Responders (or non‐responders) to pioglitazone have some distinct features from non‐responders (or responders) to canagliflozin. Collectively, a combination of pioglitazone and canagliflozin may compensate for each other's metabolic drawbacks or augment their advantages, thereby achieving overall improvements in the metabolic profiles and pathogenic defects of patients with T2DM.

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Section: Discussionmentioning

confidence: 99%

Complementary effects on glycaemic and non‐glycaemic parameters between responders and non‐responders treated with pioglitazone and canagliflozin in drug‐naive subjects with type 2 diabetes

Kutoh¹,

Kuto²,

Wada³

et al. 2021

Int J Clinical Practice

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“…Other meta-analyses have not found other SGLT-2 inhibitors to be associated with an increased risk of either fracture or AKI. 73 Last, none of the included trials reported any amputation events. Further research is needed to rule out an association and/or quantify a more precise association between ipragliflozin and these adverse events.…”

Section: Resultsmentioning

confidence: 99%

Profile of Ipragliflozin, an Oral SGLT-2 Inhibitor for the Treatment of Type 2 Diabetes: The Evidence to Date

Alkabbani¹,

Gamble²

2021

DDDT

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Background: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a novel class of pharmacotherapeutics for type 2 diabetes management that work by reducing renal reabsorption of glucose. Ipragliflozin is a potent, selective SGLT-2 inhibitor used for the management of type 2 diabetes. Objective: The primary aim of this review is to summarize the available evidence on the efficacy and safety of ipragliflozin for the management of type 2 diabetes. We also review the discovery, pharmacokinetic, and pharmacodynamic profile of ipragliflozin. Methods: To inform our review, we searched MEDLINE, International Pharmaceutical Abstracts, and Embase to identify relevant papers to ipragliflozin use in type 2 diabetes. Clinical trial registries were also searched. Results: Findings from randomized clinical trials demonstrate that compared to placebo, ipragliflozin significantly reduces glucose as measured via Hemoglobin A1c and fasting plasma glucose levels. Ipragliflozin is also associated with weight reduction and an improvement in some, but not all, cardiovascular risk markers. Ipragliflozin has a favourable safety profile with a low risk of hypoglycemia and the rates of common adverse events are not significantly different than placebo. Limited data are available to assess rare and long-term adverse effects. Conclusion:Current evidence shows that ipragliflozin is an effective therapeutic option for the management of glucose control in type 2 diabetes. However, no cardiovascular outcome trials have been conducted to date. Real-world observational studies are still needed to accurately capture any possible rare or long-term adverse events.

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“…Their results may guide decision‐making by healthcare providers, researchers and funding agencies, and inform patients and caregivers 11 . Previous overviews of SRs have focused on cancer risks and adverse events regarding the use of SGLT2 inhibitors 9,10 . The present overview summarizes the SRs' information about both the efficacy and safety of the SGLT2 inhibitor class in the treatment of T2DM.…”

Section: Discussionmentioning

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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Adverse events associated with sodium glucose co-transporter 2 inhibitors: an overview of quantitative systematic reviews

Cited by 55 publications

References 65 publications

Complementary effects on glycaemic and non‐glycaemic parameters between responders and non‐responders treated with pioglitazone and canagliflozin in drug‐naive subjects with type 2 diabetes

Complementary effects on glycaemic and non‐glycaemic parameters between responders and non‐responders treated with pioglitazone and canagliflozin in drug‐naive subjects with type 2 diabetes

Profile of Ipragliflozin, an Oral SGLT-2 Inhibitor for the Treatment of Type 2 Diabetes: The Evidence to Date

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

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