Efficacy Of Canagliflozin Research Articles

Canagliflozin alters the gut, oral, and ocular surface microbiota of patients with type 2 diabetes mellitus.

Modifications in the gut microbiota may be a crucial factor in the efficacy of canagliflozin (Cana) in managing patients with type 2 diabetes mellitus (T2DM). However, the interplay between oral and ocular surface microbiota and this treatment remains poorly explored. This study aimed to assess alterations in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment in patients with T2DM. In this 30-day, controlled before-and-after study, 21 treatment-naïve patients with T2DM received sole treatment with Cana (100 mg/day), and were matched with 10 healthy controls based on gender and age. Using 16S rRNA sequencing, changes in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment were assessed and compared with those of healthy controls. Concurrently, diabetes-related clinical parameters were recorded over the study period. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR200034878). A noticeable shift was observed in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment. The post-Cana treatment gut microbiota was more similar to that of the healthy controls. Network correlation analysis revealed that modifications in the gut, oral, and ocular surface microbiota were related to changes in clinical parameters, especially for the ocular surface microbiota. A significant decrease in fasting plasma glucose (8.22 ± 2.19 vs 6.87 ± 1.09 mmol/L), glycated serum protein [291.00 (264.00, 353.00) vs 275.00 (251.00, 342.50) μmol/L], hemoglobin A1c (7.39 ± 1.18 vs 7.12 ± 1.33%), body mass index (25.32 ± 2.99 vs 24.83 ± 2.95 kg/m2), systolic blood pressure (129.05 ± 17.51 vs 123.43 ± 14.82 mmHg), and urinary creatinine [158.40 (74.75, 219.15) vs 79.70 (56.25, 138.10) μmmol/kg] levels was noted after 30-day Cana monotherapy (P < 0.05). Treatment with Cana resulted in an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria, particularly Lachnospiraceae UCG 004, Bacteroides, and Lachnospiraceae NK4A136 group. After Cana treatment, a significant increase of Prevotella and Veillonella, both of which are known to be closely associated with SCFAs, was observed. Post-Cana administration, the ocular surface microbiota exhibited the most distinct changes in structure and composition. Remarkably, the majority of the increased ocular surface microbiota could produce SCFAs within the gut microbiota. Cana effectively improved the dysregulated glucose metabolism in patients with T2DM. This improvement can potentially be attributed to the restoration of balance among the gut, oral, and ocular surface microbial communities. https://www.chictr.org.cn/showproj.html?proj=56487, identifier ChiCTR2000034878.

The Efficacy of Canagliflozin on Type 2 Diabetic Nephropathy in Male Rats

The Efficacy of Canagliflozin on Type 2 Diabetic Nephropathy in Male Rats

The efficacy of canagliflozin in diabetes subgroups stratified by data-driven clustering or a supervised machine learning method: a post hoc analysis of canagliflozin clinical trial data.

Data-driven diabetes subgroups have shown distinct clinical characteristics and disease progression, although there is a lack of evidence that this information can guide clinical decisions. We aimed to investigate whether diabetes subgroups, identified by data-driven clustering or supervised machine learning methods, respond differently to canagliflozin. We pooled data from five randomised, double-blinded clinical trials of canagliflozin at an individual level. We applied the coordinates from the All New Diabetics in Scania (ANDIS) study to form four subgroups: mild age-related diabetes (MARD); severe insulin-deficient diabetes (SIDD); mild obesity-related diabetes (MOD) and severe insulin-resistant diabetes (SIRD). Machine learning models for HbA1c lowering (ML-A1C) and albuminuria progression (ML-ACR) were developed. The primary efficacy endpoint was reduction in HbA1c at 52 weeks. Concordance of a model was defined as the difference between predicted HbA1c and actual HbA1c decline less than 3.28 mmol/mol (0.3%). The decline in HbA1c resulting from treatment was different among the four diabetes clusters (pinteraction=0.004). In MOD, canagliflozin showed a robust glucose-lowering effect at week 52, compared with other drugs, with least-squares mean of HbA1c decline [95% CI] being 6.6 mmol/mol (4.1, 9.2) (0.61% [0.38, 0.84]) for sitagliptin, 7.1 mmol/mol (4.7, 9.5) (0.65% [0.43, 0.87]) for glimepiride, and 9.8 mmol/mol (9.0, 10.5) (0.90% [0.83, 0.96]) for canagliflozin. This superiority persisted until 104 weeks. The proportion of individuals who achieved HbA1c <53 mmol/mol (<7.0%) was highest in sitagliptin-treated individuals with MARD but was similar among drugs in individuals with MOD. The ML-A1C model and the cluster algorithm showed a similar concordance rate in predicting HbA1c lowering (31.5% vs 31.4%, p=0.996). Individuals were divided into high-risk and low-risk groups using ML-ACR model according to their predicted progression risk for albuminuria. The effect of canagliflozin vs placebo on albuminuria progression differed significantly between the high-risk (HR 0.67 [95% CI 0.57, 0.80]) and low-risk groups (HR 0.91 [0.75, 1.11]) (pinteraction=0.016). Data-driven clusters of individuals with diabetes showed different responses to canagliflozin in glucose lowering but not renal outcome prevention. Canagliflozin reduced the risk of albumin progression in high-risk individuals identified by supervised machine learning. Further studies with larger sample sizes for external replication and subtype-specific clinical trials are necessary to determine the clinical utility of these stratification strategies in sodium-glucose cotransporter 2 inhibitor treatment. The application for the clinical trial data source is available on the YODA website ( http://yoda.yale.edu/ ).

132-LB: The Safety and Efficacy of Canagliflozin in Women with Polycystic Ovary Syndrome: A Randomized Control Trial

Objectives: To determine the safety and efficacy of canagliflozin in Polycystic Ovary Syndrome (PCOS) patients with insulin resistance (IR) and investigate whether canagliflozin was non-inferiority to metformin in PCOS patients with IR. Methods: A randomized open-label study (ratio 1:1) was conducted in the department of endocrinology, Shanghai Tenth people’s Hospital between July 2019 and March 2021. PCOS women aged 18-45 years with IR were enrolled and randomly assigned to either canagliflozin 100 mg (n = 32) or metformin 1500-2000 mg (n = 35) daily for 12 weeks. The primary outcome was the changes in HOMA-IR before and after 12 weeks treatment. The secondary outcome were the changes in anthropometric, body composition, menstrual frequency, hormonal and metabolic parameters. Results: A total of 53 subjects in the canagliflozin (n=27) and metformin group (n=26) have completed follow-up. Both canagliflozin (5.4±4.1 vs. 3.2±1.9; P=0.001) and metformin (4.7±3.5 vs. 3.6±3.0; P=0.009) can significantly improve HOMA-IR after 12 weeks in PCOS patients with IR. There was no significant difference in the changes of HOMA-IR (canagliflozin: −2.3 ± 3.2 vs. metformin: -1.4 ± 2.4; P = 0.222) between the two groups. According to a secondary endpoint analysis, the canagliflozin group resulted in significantly low uric acid than the metformin group. The changes in anthropometric, body composition, menstrual frequency, sex hormone and other metabolic parameters were comparable between two groups. Gastrointestinal reaction (including nausea, vomiting and Diarrhea) (57.14 %) and pruritus vulvae (6.25%) were the main adverse events in the metformin group and Canagliflozin group, respectively. There were none serious adverse events in both groups. Conclusion: Our study showed that canagliflozin was not significantly inferior to metformin in PCOS patients with IR, which suggested SGLT2 inhibitor should be considered as an effective drug in the treatment of patients with PCOS. Disclosure M. Cai: None. Y. Zhang: None. S. Qu: None. M. Zhang: None. Funding National Natural Science Foundation of China (81601269)

2219-PUB: Comparison of Efficacy of Canagliflozin 100mg vs. Canagliflozin 300mg on hs-CRP in Patients with Type 2 Diabetes Mellitus

Aim: To compare the efficiency of canagliflozin (C1) 100mg vs. canagliflozin (C3) 300mg on highly sensitive C reactive protein (hs-CRP) and other cardio-renal (CR) biomarkers. Methodology: Between July and Sept 2018, a cohort of 190 T2DM patients aged 18-75 yrs, irrespective of baseline A1c, receiving SGLTi C1 or C3 were identified. A propensity score 1:1 matching was done for both the groups with variables that could affect treatment outcomes and to minimise confounding. Patients were evaluated every 2-3months for CR biomarkers (body mass index (BMI), A1c, systolic (S) BP, diastolic (D) BP, Lipid profile (TC, LDL, TG, HDL), Hs-CRP, creatinine, eGFR and urinary albumin/creatinine ratio {UACR}). NT-ProBNP was evaluated at 12 months. T2DM with history of IHD, revasularisation, major surgery, hyperkalemia &amp;gt;5.5Meq/L and eGFR&amp;lt;45 were excluded. Baseline characteristics were analyzed using descriptive statistics expressed as % or mean±SD. Comparison between the groups was performed using paired and unpaired t-test expressed as mean ± SE and p value &amp;lt;0.05 was considered significant(S). For interaction between drug class, ANOVA was used. Results: 44 patients were identified in C1 gr and 44 in C3 gr. Baseline characters were well matched in both gr except, SBP (mean±SD) (C1 129.05±17.54 vs. C3 138.05±22.22, P-0.38).C1 gr (baseline to 12m): there was a S reduction in hs-CRP, A1c, BMI, SBP, DBP, TC, TG, LDL. C3 gr (baseline to 12m): there was a S reduction in hs-CRP, A1c, BMI, SBP, DBP, TC, LDL. Difference between C1 and C3 at 12m: There was no difference in hs-CRP mg/L {C1 1.88±0.43 vs. C3 1.31±0.46, p-0.371}, A1c% {C1 1.27±0.19 vs. C3 1.44±0.34, p-0.666}, BMI kg/m2 {C1 1.24±0.27 vs. C3 1.23± 0.25, p-0.988}, NT-ProBNP pg/ml {C1 63.95±65.52 vs. C3 61.53±61.71, p-0.864} eGFR {C1 6.39±3.37 vs. C3 0.99±3.20, p-0.952}, UACR mg/gm {C1 25.48±10.86 vs. C3 9.61±7.87, p-0.240}, Lipid profile, SBP and DBP between both gr. Conclusion: Canagliflozin 100mg is as good as canagliflozin 300mg in reduction of hs-CRP and CR markers. Disclosure V. Gupta: None. V. Teli: None. A. Patel: None.

1962-P: Comparison of the Effects of Three SGLT2 Inhibitors on Metabolic Parameters and Insulin Sensitivity in a Nondiabetic Rat Model of Metabolic Syndrome

Studies directly comparing metabolic efficacy of various sodium glucose cotransporter-2 inhibitors (SGLT2i) are scarce. To this end, we compared the effect of SGLT2i: Empagliflozin (EMP), Canagliflozin (CAN) and Dapagliflozin (DAP) on biometric, metabolic and hormonal parameters and insulin sensitivity in hereditary hypertriglyceridemic rats (hHTG) - a non-obese model of metabolic syndrome characterized by dyslipidemia, insulin resistance and increased blood pressure. Male rats, 4 months old, were fed standard diet (C) or standard diet enriched by EMP (10mg/kg b.w./day), CAN (100mg/kg b.w./day) or DAP (10mg/kg b.w./day) for 6 weeks. All SGLT2i induced glycosuria which was 8-fold higher in CAN and DAP as compared to EMP group (Mean±SD: EMP:53±6; CAN:416±4; DAP:376±32 mmol/l; P&amp;lt;0.001). CAN decreased body weight relative to C while EMP and DAP had no significant effect. Visceral fat weight decreased in CAN and DAP compared to C (P&amp;lt;0.01). Relative weight of kidneys (g/100g b.w.) was increased in all SGLT2i groups compared to C with a less pronounced effect of EMP relative to CAN and DAP (P&amp;lt;0.01). CAN decreased both fasting and postprandial glycemia relative to other groups. Postprandial triglyceride levels were decreased by all SGLT2i compared to C (EMP: -32%; P&amp;lt;0.01; CAN: -55%; DAP -48%, P&amp;lt;0.001). 14C-palmitic acid oxidation decreased in the myocardium of CAN and DAP compared to C, whereas no significant effect of EMP was noted. CAN and EMP administration reduced liver glycogen content compared to C (P&amp;lt;0.05). Leptin levels decreased in CAN (-79%) and DAP (-56%) compared to C. GLP-1 levels increased in CAN compared to other groups while C-peptide was lower in CAN vs. C group. In conclusion, our results suggest higher efficacy of CAN compared to DAP and EMP in improving insulin sensitivity and decreasing glucose levels in a non-obese model of metabolic syndrome. The differences could be related to higher SGLT1 inhibition activity of CAN. Disclosure J. Trnovska: None. M. Hüttl: None. I. Marková: None. O. Oliyarnyk: None. H. Malinska: None. D. Miklankova: None. H. Kratochvilova: None. P. Svoboda: None. A. Cinkajzlova: None. I. Lankova: None. M. Mraz: None. M. Haluzik: None. Funding MH CZ - DRO; Institute for Clinical and Experimental Medicine (IN00023001)

Canagliflozin review - safety and efficacy profile in patients with T2DM.

Canagliflozin is a sodium glucose-cotransporter (SGLT) receptor inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM). This article reviews the mechanism of action of SGLT-2 receptor inhibitors and the efficacy of canagliflozin as an antidiabetic agent, its cardiovascular and renal benefits, and safety profile. During the development of canagliflozin, Phase II trials showed an improvement in cardiac and renal biomarkers such as blood pressure, body weight, and albuminuria. The large CANVAS program showed that canagliflozin reduced the composite cardiovascular outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The CANVAS program also showed a possible benefit of canagliflozin on a renal composite of sustained 40% reduction in estimated glomerular filtration rate, the need for renal replacement therapy, or death from renal causes. The safety profile of canagliflozin has been well characterized, and known side effects such as mycotic genital infections were confirmed in CANVAS. However, an increased risk of amputations was observed in CANVAS that requires further study. Overall, canagliflozin is an effective antidiabetic medication with cardiovascular and likely renal benefits, and with a generally well-tolerated safety profile. Results from the CREDENCE trial will further evaluate the safety and potential renal benefits of canagliflozin in patients with established diabetic nephropathy.

Efficacy of canagliflozin against nonalcoholic fatty liver disease: a prospective cohort study.

SummaryBackgroundNonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease worldwide and is characterized by insulin resistance, hepatic steatosis and often prediabetes or diabetes. Canagliflozin, a selective sodium glucose cotransporter 2 inhibitor, is a new oral anti‐diabetic drug that reduces hyperglycaemia by promoting urinary glucose excretion. Glycosuria produced by canagliflozin is associated with weight loss, mainly due to reduced fat volume and improve insulin resistance. Reduced body weight and improvement of insulin resistance by canagliflozin may be an effective treatment for NAFLD.MethodsThirty‐five patients with NAFLD (17 men and 18 women) were enrolled and administered canagliflozin (100 mg). Body weight and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma‐glutamyl transferase (γ‐GTP), low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglycerides (TG), blood sugar (BS), glycated haemoglobin (HbA1C), uric acid (UA) and ferritin, and fibrosis‐4 (FIB‐4) index values were measured at baseline and at 3‐month and 6‐month follow‐up visits.ResultsBody weight and serum levels of AST, ALT, γ‐GTP, TG, UA, HbA1C, BS and ferritin decreased significantly after 3 and 6 months of canagliflozin treatment. Serum BS levels and FIB‐4 index values decreased slightly following 3 months of treatment; these results reached significance after 6 months. Reduced serum ALT levels at 6 months were significantly correlated with baseline HbA1C and ferritin levels. Moreover, a significant correlation between reduced body weight and serum ALT levels was observed at 6 months. Decreased serum ALT levels were significantly correlated with decreased serum ferritin at 6 months.ConclusionsCanagliflozin significantly reduced the serum levels of BS, HbA1C, TG, UA and ferritin, as well as FIB‐4 index values and body weight, with improved liver function. Sodium glucose cotransporter 2 inhibitors may be an important therapeutic modality for improving liver injury in NAFLD patients.

Abstract #288 Efficacy of Canagliflozin 300 Mg in Overweight and Obese Type 2 Diabetes Mellitus Patients in a Real World Setting

Abstract #288 Efficacy of Canagliflozin 300 Mg in Overweight and Obese Type 2 Diabetes Mellitus Patients in a Real World Setting

Safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus: a 1-year post-marketing surveillance in Japan

Objective: To evaluate the safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus (T2DM) in clinical settings.Methods: The authors conducted a 1-year post-marketing surveillance (PMS) of canagliflozin in almost all the elderly patients (≥65 years old) with T2DM who began taking canagliflozin during the first 3 months after its launch in Japan. The main outcomes included the incidences of adverse drug reactions (ADRs), serious ADRs, and the changes of laboratory tests as well as efficacy variables.Results: An ADR was reported in 9.09% (125 of 1375 patients) in the safety analysis set. The main ADRs were dehydration, constipation, thirst, pollakiuria, dizziness, cystitis, eczema, pruritus, and rash. The incidence of serious ADRs was 1.02% (14 patients), which included urinary tract infection, dehydration, hypoglycemia, and cerebral infarction (two patients each). ADRs of special interest that had been reported in clinical trials of SGLT2 inhibitors, such as hypoglycemia, volume depletion-related events, genital/urinary tract infection, polyuria/pollakiuria, and ketone body increased were also observed in this PMS. The safety profiles were similar to the results of a previous clinical study of canagliflozin, and new safety concerns were not identified in this survey. The mean change in HbA1c was –0.77% after 12 months of treatment in the efficacy analysis set.Conclusion: In this PMS, the safety and efficacy profiles of canagliflozin in elderly patients with T2DM were obtained in the clinical settings in Japan and the drug was well tolerated and effective in improving glycemic control.

Long‐term safety and efficacy of canagliflozin as add‐on therapy to teneligliptin in Japanese patients with type 2 diabetes

AimTo evaluate the long‐term safety and efficacy of canagliflozin as add‐on therapy in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control with teneligliptin monotherapy.MethodsThis open‐label 52‐week study was conducted in Japan. Patients received canagliflozin 100 mg added to teneligliptin 20 mg orally once daily for 52 weeks. The safety endpoint was the incidence of adverse events (AEs). The efficacy endpoints included changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and body weight from baseline to week 52 (with last observation carried forward).ResultsOverall, 153 patients entered the treatment period and 142 completed the study. The overall incidence rates of AEs and drug‐related AEs were 69.9% and 22.9%, respectively. Most AEs and drug‐related AEs were mild or moderate in severity. There were no previously undescribed safety signals. The mean changes in HbA1c, FPG and body weight were −0.99% (95% confidence interval [CI] −1.12 to −0.85), −38.6 mg/dL (95% CI −43.4 to −33.9) and −3.92% (95% CI −4.53 to −3.31), respectively. These effects were maintained for 52 weeks without attenuation. HbA1c and body weight were both decreased in 82.24% of patients at the end of the treatment period. Reductions in postprandial glucose were observed at weeks 24 and 52.ConclusionsNo new safety risks with this combination were identified, and sustained improvements in HbA1c, FPG and body weight were observed. The findings suggest that long‐term co‐administration of canagliflozin with teneligliptin is well tolerated and effective in Japanese patients with T2DM who have inadequate glycaemic control on teneligliptin alone.

Sodium-glucose Cotransporter-2 Inhibitors: Moving Beyond the Glycemic Treatment Goal.

Revelations of the multifactorial pathogenesis of type 2 diabetes mellitus (T2DM) that extend beyond the role of insulin and glucose utilization have been crucial in redefining the treatment paradigm. The focus of treatment is currently directed towards achieving wide-ranging targets encompassing the management of cardiovascular comorbidities that have been evidenced as indispensable aspects of T2DM. While most currently prescribed antihyperglycemic agents have little or no effect on reducing cardiovascular risks, some have been associated with undesirable effects on common risk factors such as weight gain and cardiovascular sequelae. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are newer additions to the array of therapeutic agents for T2DM that have demonstrated robust glycemic control as mono and add-on therapies. Their unique renal mode of action, independent of insulin modulation, confers complementary metabolic benefits. By virtue of these effects, SGLT2i may have a distinct role in the revised treatment recommendations by established working groups such as the American Diabetes Association and the American Association of Clinical Endocrinologists that advocate a more comprehensive management of T2DM, not restricting to glycemic targets. The current review gives an overview of the changing treatment needs for T2DM and discusses the nonglycemic effects of SGLT2i. It provides an updated summary on the efficacy of canagliflozin, dapagliflozin, and empagliflozin in promoting weight loss, stabilizing blood pressure, and other favorable metabolic effects.

Efficacy of canagliflozin (CANA) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with T2DM: Results from RCTs and Real-World (RW) study

Efficacy of canagliflozin (CANA) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with T2DM: Results from RCTs and Real-World (RW) study

Efficacy of canagliflozin (CANA) in combination with metformin (MET) in patients with T2DM: Results from 3 studies

Efficacy of canagliflozin (CANA) in combination with metformin (MET) in patients with T2DM: Results from 3 studies

Abstract #296: Efficacy of Canagliflozin (CANA) in Combination with Metformin (MET) in Patients with Type 2 Diabetes Mellitus (T2dm): Results From 3 Studies

Abstract #296: Efficacy of Canagliflozin (CANA) in Combination with Metformin (MET) in Patients with Type 2 Diabetes Mellitus (T2dm): Results From 3 Studies

Rationale and design of a randomized trial to test the safety and non-inferiority of canagliflozin in patients with diabetes with chronic heart failure: the CANDLE trial.

BackgroundBecause type 2 diabetes mellitus is associated strongly with an increased risk of cardiovascular diseases, the number of patients with diabetes with chronic heart failure is increasing steadily. However, clinical evidence of therapeutic strategies in such patients is still lacking. A recent randomized, placebo-controlled trial in patients with type 2 diabetes with high cardiovascular risk demonstrated that the SGLT2 inhibitor, empagliflozin, reduced the incidence of hospitalization for heart failure. Because SGLT2 inhibitors cause a reduction in body weight and blood pressure in addition to improving glycemic control, they have the potential to exert beneficial effects on the clinical pathophysiology of heart failure. The aim of the ongoing CANDLE trial is to test the safety and non-inferiority of canagliflozin, another SGLT2 inhibitor, compared with glimepiride, a sulfonylurea agent, in patients with type 2 diabetes mellitus and chronic heart failure.MethodsA total of 250 patients with type 2 diabetes who are drug-naïve or taking any anti-diabetic agents and suffering from chronic heart failure with a New York Heart Association classification I to III will be randomized centrally into either canagliflozin or glimepiride groups (1: 1) using the dynamic allocation method stratified by age (<65, ≥65 year), HbA1c level (<6.5, ≥6.5 %), and left ventricular ejection fraction (<40, ≥40 %). After randomization, all the participants will be given the add-on study drug for 24 weeks in addition to their background therapy. The primary endpoint is the percentage change from baseline in NT-proBNP after 24 weeks of treatment. The key secondary endpoints after 24 weeks of treatment are the change from baseline in glycemic control, blood pressure, body weight, lipid profile, quality of life score related to heart failure, and cardiac and renal function.DiscussionThe CANDLE trial is the first to assess the safety and non-inferiority of canagliflozin in comparison with glimepiride in patients with type 2 diabetes with chronic heart failure. This trial has the potential to evaluate the clinical safety and efficacy of canagliflozin on heart failure.Trial registration Unique trial Number, UMIN000017669Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0381-x) contains supplementary material, which is available to authorized users.

The efficacy and safety of canagliflozin across racial groups in patients with type 2 diabetes mellitus

Objective:Canagliflozin, a sodium-glucose co-transporter 2 inhibitor, enhances urinary glucose excretion through an insulin-independent mode of action, and improves glycemic control in patients with type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of canagliflozin across racial groups.Methods:The efficacy of canagliflozin 100 mg and 300 mg was evaluated by racial group using data pooled from four placebo-controlled phase 3 studies and two placebo-controlled sub-studies of a population of patients with inadequately controlled T2DM (N = 4158). Least-squares mean changes from baseline were calculated for hemoglobin A1c (HbA1c), systolic blood pressure (SBP), body weight (BW), cholesterol, and triglycerides. Safety/tolerability evaluation included reporting of general and prespecified adverse events (AEs).Results:A total of 75% of patients were White, 13% were Asian, 4% were Black/African American, and 8% were ‘Other’ (American Indian, Alaskan Native, mixed race, Native Hawaiian or other Pacific Islander, not reported, and unknown). Baseline demographics were similar for these groups. Dose-related reductions in HbA1c, BW, and SBP were observed with both canagliflozin doses in all racial groups. Canagliflozin was generally safe and well tolerated. Treatment with canagliflozin was associated with an increased rate of genital mycotic infections (GMIs) and urinary tract infections (UTIs) in all racial groups. GMIs were observed more often in Black/African American males and males from the ‘Other’ racial group, whereas UTIs and osmotic diuresis-related AEs were less common in Asians. Key study limitations include the high proportion of White patients compared with other racial groups and the fact that included studies were not powered to evaluate racial differences.Conclusion:Canagliflozin was generally well tolerated and consistently associated with reductions in HbA1c, BW, and SBP in patients with T2DM independent of racial background. (ClinicalTrials.gov numbers: NCT01081834; NCT01106677; NCT01106625; NCT01106690; and NCT01032629.)

Safety and efficacy of canagliflozin in Japanese patients with type 2 diabetes mellitus: post hoc subgroup analyses according to body mass index in a 52-week open-label study

Background: The safety and efficacy of sodium glucose co-transporter 2 inhibitors in non-obese compared with obese patients with type 2 diabetes mellitus is unknown.Methods: We conducted post hoc analyses of the results of a 52-week open-label study of Japanese type 2 diabetes mellitus patients treated with 100 or 200 mg canagliflozin. Patients were divided into four subgroups according to their baseline body mass index (BMI): group I, BMI < 22 kg/m2; group II, BMI ≥ 22 to < 25 kg/m2; group III, BMI ≥ 25 to < 30 kg/m2 and group IV, BMI ≥ 30 kg/m2.Results: The overall safety was similar among the four BMI subgroups, although there were slight differences in terms of the incidences of hypoglycemia, asymptomatic hypoglycemia, female genital infections and proportions of patients with total ketone body levels exceeding 1000 μmol/l at any time for both canagliflozin doses. Hemoglobin A1c, fasting plasma glucose and body weight decreased significantly from baseline to week 52 at both canagliflozin doses. The changes in hemoglobin A1c, and fasting plasma glucose were not significantly different among the four BMI subgroups for either dose.Conclusion: Canagliflozin was tolerated in patients irrespective of their BMI at the start of treatment, although some caution may be needed.

Fixed-dose combinations in type 2 diabetes - role of the canagliflozin metformin combination.

Canagliflozin–metformin is one of the newest combination therapies available for the treatment of type 2 diabetes mellitus (T2DM). Canagliflozin is an inhibitor of the sodium–glucose co-transporter 2 which causes an increase in the urinary excretion of glucose. In the present article, we review the safety and efficacy of canagliflozin and metformin from data obtained from Phase III metformin add-on therapy clinical trials as there are no studies to date that specifically evaluate the combination of metformin and canagliflozin. Trials included in this review were dual-therapy trials of subjects who were already taking background metformin and were assigned to receive canagliflozin, glimepiride, or sitagliptin. The addition of canagliflozin to metformin resulted in a decrease in HbA1c of 0.73%–0.93%. Canagliflozin 100 mg was considered to be non-inferior to glimepiride and sitagliptin 100 mg with the canagliflozin 300 mg dose being statistically superior to sitagliptin and glimepiride. Other advantages of the use of canagliflozin are reduction in weight (3.3–4.0 kg) and systolic blood pressure (3.3–4.7 mmHg). The primary disadvantages are potential genital mycotic infections, hypotension, and gastrointestinal side effects from metformin. All things considered, this combination appears to be safe and effective in clinical trials and represents a promising option for the treatment of T2DM.

Efficacy of Canagliflozin (CANA) in Patients with Type 2 Diabetes Mellitus (T2DM) by Baseline Body Mass Index (BMI)

This analysis evaluated the effect of CANA versus placebo (PBO) on changes in A1C, body weight and SBP, stratified by baseline BMI.