Canagliflozin 50mg / Metformin 850mg tablets

AIMS: To compare up-to-date efficacy and safety data of sodium-glucose cotransporter-2 inhibitors (SGLT-2is) versus other metformin-containing oral dual-therapies (ODTs) in type 2 diabetes mellitus. METHODS: We updated a 2016 systematic literature review (SLR), searching MEDLINE, Embase, the Cochrane Database of Systematic Reviews, congress abstracts and SLR/meta-analysis (MA) bibliographies to identify randomised controlled trials. Two independent reviewers determined eligible studies, which were extracted and assessed using the Cochrane Risk of Bias tool. MA was conducted using random-effects pairwise models. RESULTS: from baseline at Weeks 24 and 52 between SGLT-2i plus metformin and other metformin-containing ODTs. Patients on SGLT-2i plus metformin showed a significantly lower risk of hypoglycaemia (risk ratio [RR]: 0.27, 95% CI: 0.09, 0.84) and significantly greater weight reduction (MD: -2.59; 95% CI: -4.42, -0.77), but an elevated risk of genital infection (RR: 5.08; 95% CI: 3.49, 7.38) at Week 52 compared with other ODTs. Other safety outcomes (e.g., urinary tract infections) were comparable between SGLT-2i plus metformin and other ODTs. CONCLUSION: Compared with other ODTs, SGLT-2i plus metformin exhibited overall comparable efficacy and safety, with a lower risk of hypoglycaemia and greater weight reduction at Week 52.

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Background: Bexagliflozin exerts definite efficacy in the treatment of type 2 diabetes mellitus (T2DM). However, whether this novel sodium-glucose cotransporter 2 (SGLT2) inhibitor is superior to other SGLT2 inhibitors remains to be elucidated. We therefore performed this network meta-analysis (NMA) to compare bexagliflozin with other SGLT2 inhibitors and establish an efficacy hierarchy in T2DM management. Methods: We systematically searched PubMed, Embase, Web of Science and the ClinicalTrials.gov registry for eligible randomized controlled trials (RCTs) published up to January 2026. Statistical analysis was conducted using Stata 14.0. Risk of bias was assessed by the Cochrane tool, evidence certainty was evaluated using the Confidence in Network Meta-Analysis (CINeMA) approach, and intervention ranking was performed using surface under the cumulative ranking curve (SUCRA) values. Results: This NMA included 48 studies with 26,838 patients. Bexagliflozin significantly reduced HbA1c, fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared with placebo. For HbA1c reduction, canagliflozin (300 mg, 100 mg) and empagliflozin 25 mg were more effective than bexagliflozin, while bexagliflozin was comparable to other SGLT2 inhibitors. For FPG reduction, canagliflozin 300 mg and empagliflozin 25 mg showed slightly greater effects than bexagliflozin, with no significant differences between bexagliflozin and other comparators. Bexagliflozin was superior to dapagliflozin 5 mg but slightly inferior to canagliflozin 300 mg for weight loss, while showing comparable efficacy to other SGLT2 inhibitors. It achieved similar SBP and DBP reduction to other SGLT2 inhibitors, with a significantly greater DBP-lowering effect than empagliflozin 10 mg. Bexagliflozin had a lower incidence of urinary tract infection than dapagliflozin (5 mg, 10 mg), with comparable safety to other agents and placebo. Canagliflozin 300 mg showed the best efficacy for HbA1c, FPG and weight control. Conclusion: Bexagliflozin demonstrates comparable efficacy to most SGLT2 inhibitors in T2DM patients, with a relatively prominent benefit in body weight reduction and a similar safety profile. Canagliflozin 300 mg provides more effective glycemic and weight control.

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Objectives: Canagliflozin (CANA), a kind of sodium-glucose cotransporter-2 (SGLT-2) inhibition, study in which the role of CANA monotherapy in polycystic ovary syndrome (PCOS) has been investigated, and it could become a novel option in the PCOS treatment. Nevertheless, trials focused on SGLT-2 combination therapy's efficacy, and safety in PCOS patients are limited. This randomized controlled trial compared the efficacy and safety of CANA and metformin (MET) combination therapy and MET monotherapy in endocrine and metabolic profiles of overweight and obese women with polycystic ovary syndrome (PCOS). Methods: Fifty-one overweight or obese non-diabetic PCOS women between 18 and 40 years old were enrolled. Patients were randomly allocated to receive either CANA/MET or MET treatment. The CANA/MET group received CANA 100 mg once daily plus MET 1000 mg twice daily, while the MET group received MET 1000 mg twice daily for three months. Changes in menstrual pattern, anthropometric parameters, gonadal parameters, glucose and lipid homeostasis, and adverse events (AEs) were evaluated. Results: Compared with the MET group, women have a significantly lower level of total testosterone (TT), area under the curve for glucose (AUCGlu), and area under the curve for insulin (AUCIns) to AUCGlu ratio in the combination group. There were no significant differences in menstrual frequency, body weight, body mass index, follicle-stimulating hormone, luteinizing hormone, free androgen index, sex hormone-binding globulin, androstenedione, fasting blood glucose, fasting insulin, AUCIns, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), and APO B/A1 ratio. AEs were seen in 57.70% (15/26) and 68.00% (17/25) of patients in the CANA/MET and MET groups, respectively. Conclusions: In overweight and obese women with PCOS, CANA and MET combination therapy may be similar to MET monotherapy in improving menstrual frequency, weight control, hyperandrogenemia, and relieving insulin resistance. CANA/MET may have more benefits in reducing TT, AUCGlu, and the AUCIns/AUCGlu ratio within three months than MET monotherapy. Trial registration: ClinicalTrials.gov, NCT04973891.

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Diabetes mellitus and cancer are two expanding global health burdens that share upstream determinants, yet diabetes may also contribute to malignancy risk through hyperglycaemia/AGE-related stress, insulin resistance with compensatory hyperinsulinaemia, obesity-related inflammation, and tumour microenvironment modulation. This narrative review synthesizes mechanistic plausibility and critically appraises the highest-level clinical evidence on the oncologic safety signals of glucose-lowering therapies, with a focus on cancer incidence captured within randomized diabetes trials. argeted searches of PubMed/MEDLINE and Embase were complemented by manual reference screening. Mechanistic and translational data were summarized separately from clinical evidence. For each drug class, we prioritized pivotal randomized controlled trials and cardiovascular outcome trials (phase 3–4, large, practice-defining), extracting malignancy reporting collected as adverse events/serious adverse events or events of special interest. When randomized evidence was limited, high-quality meta-analyses and selected real-world studies were used for context, clearly distinguished from prespecified randomized evidence. Metformin shows a predominantly neutral effect on cancer incidence, with possible indirect protective signals but no trials specifically designed to assess chemoprevention. Thiazolidinediones demonstrate an overall neutral malignancy profile, with early concerns regarding bladder cancer not confirmed in adjudicated analyses. GLP-1 receptor agonists and dual GLP-1/GIP agonists consistently show no increase in overall or site-specific cancer risk, with emerging signals of reduced obesity-related malignancies. SGLT2 inhibitors display class-wide oncologic neutrality, with heterogeneous and inconclusive drug-specific patterns in meta-analyses. Randomized evidence confirms that insulin, including long-acting analogues, does not increase cancer risk. Current randomized evidence supports a predominantly neutral effect of antidiabetic therapies on cancer incidence, with some agents showing promising signals of protection. This interpretation is constrained by non-prespecified endpoints, limited oncologic adjudication, short follow-up relative to tumour latency, low site-specific event counts, and potential competing-risk effects. Dedicated long-term trials and registry-linkage strategies with cancer-focused endpoints are needed to clarify whether any therapies confer true protection or warrant targeted monitoring.

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OBJECTIVE: To evaluate the effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in type 2 diabetes mellitus inadequately controlled with metformin monotherapy. RESEARCH DESIGN AND METHODS: This was a double-blind, placebo-controlled, parallel-group, multicenter, dose-ranging study in 451 subjects randomized to canagliflozin 50, 100, 200, or 300 mg once daily (QD) or 300 mg twice daily (BID), sitagliptin 100 mg QD, or placebo. Primary end point was change in A1C from baseline through week 12. Secondary end points included change in fasting plasma glucose (FPG), body weight, and overnight urinary glucose-to-creatinine ratio. Safety and tolerability were also assessed. RESULTS: Canagliflozin was associated with significant reductions in A1C from baseline (7.6-8.0%) to week 12: -0.79, -0.76, -0.70, -0.92, and -0.95% for canagliflozin 50, 100, 200, 300 mg QD and 300 mg BID, respectively, versus -0.22% for placebo (all P < 0.001) and -0.74% for sitagliptin. FPG was reduced by -16 to -27 mg/dL, and body weight was reduced by -2.3 to -3.4%, with significant increases in urinary glucose-to-creatinine ratio. Adverse events were transient, mild to moderate, and balanced across arms except for a non-dose-dependent increase in symptomatic genital infections with canagliflozin (3-8%) versus placebo and sitagliptin (2%). Urinary tract infections were reported without dose dependency in 3-9% of canagliflozin, 6% of placebo, and 2% of sitagliptin arms. Overall incidence of hypoglycemia was low. CONCLUSIONS: Canagliflozin added onto metformin significantly improved glycemic control in type 2 diabetes and was associated with low incidence of hypoglycemia and significant weight loss. The safety/tolerability profile of canagliflozin was favorable except for increased frequency of genital infections in females.

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Metformin is a safe and effective glucose-lowering agent, widely regarded as the first-line treatment option for type 2 diabetes (T2D), and available at very low cost. Recent updates to the American Diabetes Association (ADA) Standards of Care guidance demonstrate a shift towards the earlier use of newer, more expensive, anti-diabetic agents for the treatment of T2D, based on concurrent conditions such as cardiovascular and/or renal complication reduction, and significant weight loss. As of 2026, this has culminated in sodium-glucose cotransporter 2 inhibitors (SGLT2is) being recommended for patients with T2D and established atherosclerosis cardiovascular disease (ASCVD) or indicators of high ASCVD, heart failure or chronic kidney disease, independently of the use of metformin. The main evidence base supporting the use of SGLT2is in these patient populations come from cardiovascular and renal outcome trials, which recruited patients usually with long-standing T2D and high levels of cardiovascular and/or renal comorbidities. Whether the cardiovascular and renal benefits shown during these trials are generalisable to the early T2D or even pre-diabetic population may be debated. Ultimately, this leaves the question as to whether patients with early T2D and no cardiovascular and/or renal complications should receive treatment with SGLT2is, at a higher cost, where clinical evidence of superiority to established therapies like metformin are scarce. As T2D is a chronic, progressive disease, often advancing through pre-diabetes, early T2D and eventually treatment intensification, the cost-effectiveness of treatments at each stage of the disease must also be considered to understand the long-term economic burden. This review explores the available cost-effectiveness evidence, supported by clinical data, for the use of metformin and SGLT2is across the complete T2D continuum.

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Diabetic Kidney Disease (DKD) is a major microvascular complication for diabetic patients and is the most common cause of chronic kidney disease (CKD) and end-stage renal disease. Antidiabetic drugs, such as metformin and canagliflozin, have been shown to exert renoprotective effects. Additionally, quercetin recently showed promising results for the treatment of DKD. However, the molecular pathways through which these drugs exert their renoprotective effects remain partly unknown. The current study compares the renoprotective potential of metformin, canagliflozin, metformin + canagliflozin, and quercetin in a preclinical rat model of DKD. By combining streptozotocin (STZ) and nicotinamide (NAD) with daily oral N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME) administration, DKD was induced in male Wistar Rats. After two weeks, rats were assigned to five treatment groups, receiving vehicle, metformin, canagliflozin, metformin + canagliflozin, or quercetin for a period of 12 weeks by daily oral gavage. Non-diabetic vehicle-treated control rats were also included in this study. All rats in which diabetes was induced developed hyperglycemia, hyperfiltration, proteinuria, hypertension, renal tubular injury and interstitial fibrosis, confirming DKD. Metformin and canagliflozin, alone or together, exerted similar renoprotective actions and similar reductions in tubular injury and collagen accumulation. Renoprotective actions of canagliflozin correlated with reduced hyperglycemia, while metformin was able to exert these effects even in the absence of proper glycemic control. Gene expression revealed that the renoprotective pathways may be traced back to the NF-κB pathway. No protective effect was seen with quercetin. In this experimental model of DKD, metformin and canagliflozin were able to protect the kidney against DKD progression, albeit in a non-synergistic way. These renoprotective effects may be attributable to the inhibition of the NF-κB pathway.

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