Canagliflozin – something new for type 2 diabetes, but is it safe and efficacious?

Doggrell, Sheila A; McIntyre, Kerry L.

doi:10.1517/14656566.2014.868885

Cited by 7 publications

(4 citation statements)

References 13 publications

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“…It was thought to be due to increased urinary glucose which may act as a potential fungal growth factor in SGLT2-i treated patients (32). These studies have raised concerns about the safety testing of SGLT2-i with regards to the higher incidence of genital infections (33,34). We didn't find the higher risk of urinary tract infection in SGLT2-i plus metformin compared with metformin monotherapy.…”

Section: Discussionmentioning

confidence: 87%

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus with inadequate glycemic control on metformin: a meta-analysis

Zhang¹,

Li²,

Liu³

et al. 2019

Archives of Endocrinology and Metabolism

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Objectives To provide a meta-analysis of the clinical efficacy and safety of sodium glucose co-transporter 2 inhibitors (SGLT2-i), as a combination treatment with metformin in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with metformin alone. Materials and methods We have searched randomized controlled trials (RCTs) in the database: MEDLINE, Embase and Cochrane Collaborative database. We used mean differences (MD) to assess the efficacy of glycemic and other clinical parameters, and risk ratios (RR) to evaluate the adverse events for safety endpoints. The heterogeneity was evaluated by I 2 . Results Finally 9 studies were included. SGLT2-i plus metformin had higher reduction level in HbA1C [MD = -0.50, 95% CI (-0.62, -0.38), p < 0.00001], FPG [MD = -1.12, 95%CI (-1.38, -0.87), p < 0.00001], body weight [MD = -1.72, 95% CI (-2.05, -1.39), p < 0.00001], SBP [MD = -4.44, 95% CI (-5.45, -3.43), p < 0.00001] and DBP [MD = -1.74, 95% CI (-2.40, -1.07), p < 0.00001] compared with metformin monotherapy. However, SGLT2-i plus metformin group had higher risk of genital infection [RR = 3.98, 95% CI (2.38, 6.67), p < 0.00001]. No significant difference was found in the risk of hypoglycemia, urinary tract infection or volume related adverse events. Conclusions Although the risk of genital infection may increase, SGLT2-i plus metformin may provide an attractive treatment option to those T2DM patients who are unable to achieve glycemic control with metformin alone, based on its effects on glycemic control, reducing body weight and lowering blood pressure.

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Section: Discussionmentioning

confidence: 87%

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus with inadequate glycemic control on metformin: a meta-analysis

Zhang¹,

Li²,

Liu³

et al. 2019

Archives of Endocrinology and Metabolism

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“…A randomized, doubled-blind placebo-controlled study to examine the safety and tolerability of canagliflozin indicated upper respiratory tract infection as adverse effects reported in over 3% of patients [35]. Federal Drug Administration (FDA) has recently approved canagliflozin for use in type 2 diabetes, while directing that a clinical outcome safety trial be undertaken [36]. Dual SGLT1/SGLT2 inhibitors, such as canagliflozin [37] and LX4211 [38], have been introduced in the diabetes pharmacopeia; however, bronchial inflammation, airway damage and reduction of survival rate should be considered in patients with sepsis.…”

Section: Discussionmentioning

confidence: 99%

Effects of salbutamol and phlorizin on acute pulmonary inflammation and disease severity in experimental sepsis

et al. 2019

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Respiratory infection can be exacerbated by the high glucose concentration in the airway surface liquid (ASL). We investigated the effects of salbutamol and phlorizin on the pulmonary function, oxidative stress levels and SGLT1 activity in lung, pulmonary histopathological damages and survival rates of rats with sepsis. Sepsis was induced by cecal ligation and puncture surgery (CLP). Twenty-four hours after surgery, CLP rats were intranasally treated with saline, salbutamol or phlorizin. After 2 hours, animals were anesthetized and sacrificed. Sepsis promoted atelectasis and bronchial inflammation, and led to increased expression of SGLT1 on cytoplasm of pneumocytes. Salbutamol treatment reduced bronchial inflammation and promoted hyperinsuflation in CLP rats. The interferon-ɤ and Interleucin-1β concentrations in bronchoalveolar lavage (BAL) were closely related to the bronchial inflammation regulation. Salbutamol stimulated SGLT1 in plasma membrane; whereas, phlorizin promoted the increase of SGLT1 in cytoplasm. Phlorizin reduced catalase activity and induced a significant decrease in the survival rate of CLP rats. Taken together, sepsis promoted atelectasis and lung inflammation, which can be associated with SGLT1 inhibition. The loss of function of SGLT1 by phlorizin are related to the augmented disease severity, increased atelectasis, bronchial inflammation and a significant reduction of survival rate of CLP rats. Alternatively salbutamol reduced BAL inflammatory cytokines, bronchial inflammation, atelectasis, and airway damage in sepsis. These data suggest that this selective β2-adrenergic agonist may protect lung of septic acute effects.

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“…Such observations have raised concerns about the safety testing of SGLT2 inhibitors with regards to the higher incidence of genital infections. [37,38] …”

Section: Discussionmentioning

confidence: 99%

Long-term efficacy and safety of sodium-glucose cotransporter-2 inhibitors as add-on to metformin treatment in the management of type 2 diabetes mellitus

Li¹,

Gong²,

Li³

et al. 2017

Medicine

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Background:Drug intensification is often required for patients with type 2 diabetes mellitus on stable metformin therapy. Among the potential candidates for a combination therapy, sodium-glucose transporter-2 (SGLT2) inhibitors have shown promising outcomes. This meta-analysis was performed to compare the efficacy and safety of SGLT2 inhibitors with non-SGLT2 combinations as add-on treatment to metformin.Methods:Literature search was carried out in multiple electronic databases for the acquisition of relevant randomized controlled trials (RCTs) by following a priori eligibility criteria. After the assessment of quality of the included RCTs, meta-analyses of mean differences or odds ratios (OR) were performed to achieve overall effect sizes of the changes from baseline in selected efficacy and safety endpoints reported in the individual studies. Between-studies heterogeneity was estimated with between-studies statistical heterogeneity (I2) index.Results:Six RCTs fulfilled the eligibility criteria. SGLT2 inhibitors as add-on to metformin treatment reduced % HbA1c significantly more than non-SGLT2 combinations after 52 weeks (P = .002) as well as after 104 weeks (P < .00001). Among other endpoints, SGLT2 inhibitors also reduced fasting plasma glucose levels, body weight, systolic, and diastolic blood pressures after 52 weeks and 104 weeks significantly (P < .00001) more than non-SGLT2 combinations. Incidence of hypoglycemia was significantly lower (P = .02) but incidence of suspected or confirmed genital tract infections was significantly higher (P < .00001) in SGLT2 inhibitors treated in comparison with non-SGLT2 combinations.Conclusion:As add-on to metformin treatment, SGLT2 inhibitors are found significantly more efficacious than non-SGLT2 inhibitor combinations in the management of type 2 diabetes mellitus, although, SGLT2 inhibitor therapy is associated with significantly higher incidence of suspected or confirmed genital tract infections.

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Canagliflozin – something new for type 2 diabetes, but is it safe and efficacious?

Cited by 7 publications

References 13 publications

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus with inadequate glycemic control on metformin: a meta-analysis

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus with inadequate glycemic control on metformin: a meta-analysis

Effects of salbutamol and phlorizin on acute pulmonary inflammation and disease severity in experimental sepsis

Long-term efficacy and safety of sodium-glucose cotransporter-2 inhibitors as add-on to metformin treatment in the management of type 2 diabetes mellitus

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