Nonsteroidal MRAs: A New Hope for Improved Cardiorenal Outcomes in Patients with CKD and T2D

Dr Shashank Joshi, Mumbai

• Chronic kidney disease (CKD) progression in type 2 diabetes (T2D) is driven by the combined effects of metabolic, hemodynamic, inflammatory and fibrotic factors. Inflammation and fibrosis are potential treatment targets to address the residual risk in CKD and T2D.
• Mineralocorticoid receptor (MR) overactivation is a major driver of kidney damage.
• MR overactivation, which contributes to inflamma­tion and fibrosis, is a potential treatment target to slow CKD progression.
• Finerenone, a novel, nonsteroidal, selective mineralo­corticoid receptor antagonist (MRA), blocks MR overactivation and reduces albuminuria.
• Finerenone is different from available steroidal MRAs. Finerenone is hypothesized to slow CKD progre­ssion and prevent cardiovascular (CV) events by directly targeting inflammation and fibrosis.
• FIDELIO-DKD and FIGARO-DKD results indicate that finerenone is an effective investigational treatment option for CV and kidney protection in patients with CKD stage 1-4 and T2D.

Gen 2.0 Basal Insulin: Leveraging Time-in-Range to Improve Patient Outcomes

Dr Jothydev Kesavadev, Thiruvananthapuram

• Time-in-range (TIR) and glucose variability (GV) have emerged integral in diabetes management.
• In range is the first randomized clinical trial comparing TIR and GV of the two second-generation basal insulin, in adults with type 1 diabetes mellitus (T1DM). The trial met the primary end point of noninferiority of U300 glargine vs. U100 degludec with respect to TIR. The GV, hypoglycemic episodes and safety were also comparable.
• We need to adopt better, newer therapies so as to prevent microvascular complications in diabetes.

Cardiorenal Metabolic Disorder, is the Panacea Available Now?

Dr Mangesh Tiwaskar, Mumbai

“It should be the function of medicine to have people die young as late as possible.” —Ernest L Wynder

• Diabetes treatment for cardiovascular disease (CVD) reduction is categorized in two arms, i.e., sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor (GLP-1R) anta­gonists with hemodynamic effect and anti-athero­genic effect mechanism of action, respectively.
• SGLT2 inhibitors improve ventricular loading conditions (diuresis, natriuresis, etc.), myocardial energetics, TGF, IGH, etc. by modulating sympa­thetic nervous system (SNS) activity.
• GLP-1R on the other hand has anti-inflammatory effects, reduces oxidative stress, inhibits renin-angiotensin-aldosterone system (RAAS), increases natriuresis, etc.
• SGLT2 inhibitors and GLP-1R provide complete CV renal protection combined and are a challenge.

SGLT2 Inhibitor is 2nd Add-on for Everyone

Dr Piyush Desai, Surat

• Over the last 5 years, several landmark trials such as EMPA-REG, CANVAS, CREDENCE, DAPA-HF and KDIGO have shown the multidimensional action of SGLT2 inhibitors in diabetes therapy and reducing the risk of CV renal outcomes.
• Based on this evidence, American Diabetes Association (ADA) and American Association of Clinical Endocrinologists (AACE) guidelines have been changed and recommend early prescription of SGLT2 inhibitors for patients with a high risk of ASCVD, CKD, HF, etc.
• According to AACE guidelines, SGLT2 inhibitors can be used in combination with metformin, if the entry-level HbA1c is high.

SGLT2 inhibitor is a cost-effective drug that when reduces weight and the risk of hypoglycemia along with controlling several other risk factors.