Canagliflozin 50mg / Metformin 1g tablets

Aims/hypothesisThe aim of this work was to evaluate the efficacy and safety of canagliflozin vs placebo and sitagliptin in patients with type 2 diabetes who were being treated with background metformin.MethodsThis randomised, double-blind, four-arm, parallel-group, Phase 3 study was conducted at 169 centres in 22 countries between April 2010 and August 2012. Participants (N = 1,284) with type 2 diabetes aged ≥18 and ≤80 years who had inadequate glycaemic control (HbA1c ≥7.0% [53 mmol/mol] and ≤10.5% [91 mmol/mol]) on metformin therapy received canagliflozin 100 mg or 300 mg, sitagliptin 100 mg, or placebo (n = 368, 367, 366, 183, respectively) for a 26 week, placebo- and active-controlled period followed by a 26 week, active-controlled period (placebo group switched to sitagliptin [placebo/sitagliptin]) and were included in the modified intent-to-treat analysis set. Randomisation was performed using a computer-generated schedule; participants, study centres and the sponsor were blinded to group assignment. The primary endpoint was change from baseline in HbA1c at week 26; secondary endpoints included changes in HbA1c (week 52) and fasting plasma glucose (FPG), body weight, and systolic blood pressure (BP; weeks 26 and 52). Adverse events (AEs) were recorded throughout the study.ResultsAt week 26, canagliflozin 100 mg and 300 mg reduced HbA1c vs placebo (−0.79%, –0.94%, –0.17%, respectively; p < 0.001). At week 52, canagliflozin 100 mg and 300 mg demonstrated non-inferiority, and canagliflozin 300 mg demonstrated statistical superiority, to sitagliptin in lowering HbA1c (−0.73%, –0.88%,–0.73%, respectively); differences (95% CI) vs sitagliptin were 0% (−0.12, 0.12) and −0.15% (−0.27, –0.03), respectively. Canagliflozin 100 mg and 300 mg reduced body weight vs placebo (week 26: –3.7%, –4.2%, –1.2%, respectively; p < 0.001) and sitagliptin (week 52: –3.8%, –4.2%, –1.3%, respectively; p < 0.001). Both canagliflozin doses reduced FPG and systolic BP vs placebo (week 26) and sitagliptin (week 52) (p < 0.001). Overall AE and AE-related discontinuation rates were generally similar across groups, but higher with canagliflozin 100 mg. Genital mycotic infection and osmotic diuresis-related AE rates were higher with canagliflozin; few led to discontinuations. Hypoglycaemia incidence was higher with canagliflozin.Conclusions/interpretationCanagliflozin improved glycaemia and reduced body weight vs placebo (week 26) and sitagliptin (week 52) and was generally well tolerated in patients with type 2 diabetes on metformin.Clinical trial registryClinicalTrials.gov NCT01106677FundingThis study was supported by Janssen Research & Development, LLC.

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IntroductionPolycystic ovary syndrome is a common chronic condition characterized by insulin resistance and hyperandrogenism, leading to significant health risks and impaired quality of life. Sodium-glucose transporter type 2 inhibitors have shown promise in improving the metabolic profile of women with polycystic ovary syndrome. However, their impact on hormonal parameters and cycle disorders remains uncertain.MethodsThis systematic review analyzed randomized clinical trials published up to 1 December 2023, comparing sodium-glucose transporter type 2 inhibitors to metformin, other antidiabetic agents, or placebo in women with polycystic ovary syndrome. The primary outcomes were changes in total testosterone, free androgen index, dehydroepiandrosterone sulfate, delta-4 androstenedione, and cycle disorders.ResultsFive randomized studies were included, evaluating canagliflozin, dapagliflozin, licogliflozin, or empagliflozin against metformin, exenatide, or placebo, with a total of 214 participants. Improvements in total testosterone and dehydroepiandrosterone sulfatewere observed in some studies, but the effects were inconsistent across drugs and outcomes. Additionally, two studies reported beneficial effects on cycle disorders.ConclusionsSodium-glucose transporter type 2 inhibitors appear to have a potential but variable impact on hormonal parameters in women with polycystic ovary syndrome. However, larger and longer-duration studies are needed to fully elucidate their long-term efficacy in addressing hyperandrogenism and improving overall outcomes in these patients.

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AimsTo 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.MethodsWe 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.ResultsWe included 36 publications (23 unique studies). Mean differences (MD) indicated comparable change in HbA1c 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.ConclusionCompared 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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BackgroundBexagliflozin 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.MethodsWe 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.ResultsThis 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.ConclusionBexagliflozin 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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IntroductionAchieving and sustaining target glycated haemoglobin (HbA1c) levels is fundamental in the management of type 2 diabetes (T2D). We here aimed to assess whether initial dual oral therapy outperforms monotherapy in reaching glycaemic targets in patients with treatment-naive or early-stage T2D.MethodsThis systematic review and meta-analysis were registered with PROSPERO (CRD420251111096). Parallel-group randomised controlled trials with a duration of at least 12 weeks were identified through searches of PubMed and the Cochrane Library spanning 2005 to 2025. Data at the trial arm level, including baseline and endpoint HbA1c values, were extracted for seven predefined comparisons and combined using a random-effects inverse-variance meta-analysis in R version 4.3.1 (meta package). The primary outcome was the proportion of treatment arms achieving an HbA1c level of ≤7.5% (58 mmol/mol). Secondary outcomes included the proportions achieving HbA1c levels of ≤7.0% (53 mmol/mol) and ≤6.5% (48 mmol/mol), as well as mean differences in HbA1c levels.ResultsA total of 20 trials, encompassing 37 treatment arms, were analysed. Dual combination therapy consistently demonstrated superior efficacy compared to monotherapy. The proportion of patients achieving HbA1c levels of ≤7.5% (58 mmol/mol) was 86% with initial dual therapy versus 82% with initial monotherapy (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.20-1.47, p = 0.002). At the more stringent threshold of ≤7.0% (53 mmol/mol), the rates were 69% versus 64% (OR 1.27, p = 0.003), and at ≤6.5% (48 mmol/mol), 42% versus 39% (OR 1.18, p = 0.056). When comparing initial dual therapy to metformin monotherapy, the respective achievement rates were 86% versus 81% (OR 1.41, p = 0.001) for a target of ≤7.0% (53 mmol/mol). The combination of metformin with a sodium-glucose cotransporter 2 inhibitor (SGLT2-i) resulted in 88% reaching ≤7.5% (58 mmol/mol), compared to 81% with metformin alone (OR 1.55, p ≤ 0.001), a difference significant across all thresholds. Dual therapy containing SGLT-2i achieved 87% at ≤7.5% (58 mmol/mol), compared with 82% with all monotherapies (OR 1.43, p ≤ 0.001). SGLT-2i monotherapy itself led to 89% reaching the target, compared with 81% with metformin (OR 1.73, p ≤ 0.001). No significant difference in outcome was observed between dual and monotherapy involving SGLT2-is (OR 0.87, p = 0.480). The pooled final HbA1c values were 6.7% (50 mmol/mol) for dual therapy and 7.9% (63 mmol/mol) for monotherapy, corresponding to a mean difference of -0.45% (95% CI -0.60 to -0.25, p ≤ 0.001). Heterogeneity among studies was low to moderate (I2 25%-50%), and results remained consistent after excluding rosiglitazone arms.ConclusionsInitial dual therapy, particularly combining metformin with an SGLT2-i, results in superior achievement of HbA1c targets across various thresholds compared to monotherapy. SGLT2-i alone surpasses metformin alone in efficacy. Adding a second agent to SGLT2-i did not provide additional glucose-lowering benefit to SGLT2-i monotherapy. Early initiation of SGLT2-i monotherapy or combination therapy should be considered upon diagnosis of T2D.

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BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by insulin resistance and hyperandrogenism; whether novel antidiabetic drugs differentially improve these metabolic and reproductive disturbances remains uncertain. We performed a network meta-analysis to simultaneously rank the efficacy and safety of sodium–glucose cotransporter-2 inhibitors (SGLT-2i), GLP-1 receptor agonists (GLP-1RAs) and DPP-4 inhibitors (DPP-4i) in women with PCOS. METHODS: We searched PubMed, Web of Science, Medline, Cochrane CENTRAL and Embase to 6 June 2025 for randomized controlled trials (RCTs) that compared SGLT-2i, GLP-1RAs or DPP-4i with placebo or active drugs in women ≥ 18 years with PCOS. Primary endpoints were Body Mass Index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), total testosterone (TT) and free androgen index (FAI); secondary endpoints included waist circumference (WC), Sex Hormone Binding Globulin (SHBG), fasting blood glucose (FBG), lipids and gastrointestinal adverse events. A frequentist random-effects network meta-analysis was conducted in Stata 15.1; treatments were ranked with SUCRA (0–100%) and certainty was appraised with CINeMA. RESULTS: 29 RCTs (1771 participants) were eligible. SGLT-2i yielded the largest reduction in BMI (mean difference vs. placebo − 4.26 kg m⁻², 95% CI − 6.01 to − 2.52; SUCRA 91%) and HOMA-IR (–2.56, − 4.53 to − 0.59; SUCRA 89%). The metformin plus GLP-1RAs combination produced the greatest decrease in TT (–1.35 ng mL⁻¹ vs. placebo, − 2.22 to − 0.48; SUCRA 85%) and FAI (–1.91, − 3.43 to − 0.40; SUCRA 82%), and also led improvements in WC, SHBG and FBG. SGLT-2i ranked first for lowering triglycerides (TG) and total cholesterol (TC). GLP-1RAs monotherapy carried the highest risk of nausea (OR 6.26–9.20), vomiting (OR up to 26.56) and abdominal pain, whereas metformin/DPP-4i markedly increased diarrhoea (OR 2 704 vs. placebo). No statistical inconsistency or publication bias was detected; certainty was high for selected contrasts but moderate to very low for most comparisons. CONCLUSIONS: SGLT-2i provide the most favourable cardiometabolic profile as single agents for weight and insulin resistance in PCOS, whereas metformin combined with GLP-1RAs most effectively attenuates hyperandrogenism at the price of greater gastrointestinal intolerance. The low certainty of much of the evidence underscores the need for large, long-term RCTs to confirm these findings. SYSTEMATIC REVIEW REGISTRATION: CRD420251045700.

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