Fixed-Dose Combination of Canagliflozin and Metformin as an Adjunct to Diet and Exercise in Indian Adults with Type 2 Diabetes Mellitus: Results from a Multicentric, Open-Label, Single-Arm, Phase IV Study.

BACKGROUND: Canagliflozin and metformin fixed-dose combination (CANA/MET FDC), an approved treatment for type 2 diabetes mellitus (T2DM) in India, effectively lowers glycated hemoglobin (HbA1c), promotes weight loss, and improves patient adherence. As a regulatory requirement, we aimed to evaluate the safety and efficacy of CANA/MET FDC in Indian patients with T2DM. RESEARCH DESIGN AND METHODS: This prospective, multicenter, open-label, single-arm, phase IV study included Indian patients with T2DM (aged 18-65 years) inadequately controlled on diet and exercise. Patients received CANA/MET (50/500 and 50/1000 mg) immediate-release (IR) FDC twice daily for 24 weeks. The primary endpoint was safety assessment, including adverse events (AEs) and serious AEs (SAEs). The secondary endpoint included a change in HbA1c from baseline to weeks 12 and 24. Descriptive statistics were used for all continuous safety variables and efficacy parameters. RESULTS: Of the 310 patients screened, 276 were enrolled. 114/274 (41.6%) patients had ≥1 treatment-emergent AE [treatment-emergent AEs (TEAEs), among which 29 (10.6%) were related to study intervention]. The most common TEAEs were dyslipidemia (4.7%), pyrexia (4.7%), genital infections (3.3%), hypoglycemia (3.3%), and urinary tract infections (2.6%). Three (1.1%) patients had serious TEAEs, and all cases were resolved. No deaths were reported. The mean change in HbA1c from baseline was -0.92 and -0.93% at weeks 12 and 24, respectively. CONCLUSION: The study demonstrates the safety and efficacy of CANA/MET FDC in Indian patients with T2DM, presenting a safe therapeutic option for diabetes management in India.

SGLT2 Inhibitors: Paradigm Shift from Diabetes Care to Metabolic Care-An Indian Perspective.

The prevalence and burden of diabetes are on the rise in India, making it 'the diabetes capital of the world'. Comorbidities such as obesity, cardiovascular (CV) complications, chronic kidney disease (CKD), non-alcoholic fatty liver disease (NAFLD), and neurodegenerative diseases are common in patients with diabetes. Recent breakthroughs in diabetes medications and continuous glucose monitoring have resulted in a paradigm shift in diabetes care. Hence, a review in the Indian context is warranted. This review focuses on the existing evidence (gathered by a systematic literature search utilising online databases such as PubMed) on the metabolic, cardio-renoprotective, and hepatoprotective effects of sodium-glucose co-transporter 2 (SGLT2) inhibition, particularly in the Indian setting. The study revealed that the SGLT2 inhibitors (SGLT2i), with their numerous pleiotropic benefits, have received considerable attention recently as a novel class of antihyperglycaemic agents (AHAs) for the management of diabetes. SGLT2i play a crucial role in the transition from glycaemic control to metabolic care, particularly in the context of obesity, CV disease and renal disease. In addition to improving glycaemic control, SGLT2i have been shown to promote weight loss, reduce blood pressure and improve lipid profiles, which are key components of metabolic health. Moreover, SGLT2i have demonstrated renal protective effects, including a reduction in albuminuria and a slower decline in the estimated glomerular filtration rate (eGFR), suggesting a potential role in the management of renal dysfunction.

Hypolipidaemic Effects of Gymnema sylvestre on High Fat Diet Induced Dyslipidaemia in Wistar Rats.

INTRODUCTION: Hyperlipidaemia is a well known risk factor for cardiovascular diseases. Lifestyle modification can be the initial step to reduce cholesterol levels. There are various drugs which are used to control dyslipidaemia. Treatment of lipid abnormalities is a lifelong battle. Moreover, the safety and effectiveness of long term lipid lowering treatment are questionable. Gymnema Sylvestre (GS) is a well known herb with various medicinal properties. AIM: To explore the hypolipidaemic activity of GS leaves extract. MATERIALS AND METHODS: Adult healthy female wistar rats, 30 in number, divided into five groups, weighing 150- 200 g were used. Dyslipidaemia was induced in rats by feeding them on high fat diet for four weeks. For the next four weeks GS extract was used as test drug while Atorvastatin was used as standard drug. Blood sample was collected for estimation of lipid profile on day 0, week 4 and week 8. Data was recorded as mean±SEM (Standard error of mean). Paired t-test and one way Analysis of Variance (ANOVA) followed by Dunnett's post hoc test was used for comparison. A p-value <0.05 was considered statistically significant. SPSS Statistics 20 (IBM software) was used for the analysis. RESULTS: Feeding rats with high fat diet for four weeks led to obesity and dyslipidaemia in rats. GS at both the doses (100mg/kg and 200mg/kg) significantly improved the lipid profile. Total Cholesterol (TC), Triglycerides (TG), Very Low Density Lipoprotein (VLDL) and Low Density Lipoprotein (LDL) values reduced significantly while that of High Density Lipoprotein (HDL) increased significantly. GS 200 mg/kg was found more effective than GS 100 mg/kg. GS improved the value of lipid profile significantly but the effect was found inferior to Atorvastatin. CONCLUSION: From the present study it can be concluded that GS possess an effective hypolipidaemic effect. Hence it can be included as an add on therapy in dyslipidaemia after further confirmatory studies.