Current Role of Dapagliflozin in Clinical Practice.

Dapagliflozin is the first in a novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors which was approved by USFDA in management of type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise to improve glycemic control in adults initially, followed by to reduce the risk of hospitalization for heart failure (HHF) in adults with T2DM and established cardiovascular disease or multiple cardiovascular risk factors. Most recently, it is approved to reduce the risk of cardiovascular death and in adults with heart failure (HF) with reduced ejection fraction (NYHA class II-IV). Dapagliflozin has been studied in a wide range of patients with diabetes and plethora of evidence has confirmed its efficacy as a monotherapy as well as an add-on to the oral therapies and insulin, when compared to placebo. Additional advantages include weight reduction which has been consistently demonstrated in Phase III studies and good tolerability. Also there is a demonstrable reduction in systolic blood pressure in patients treated with SGLT2 inhibitors. DECLARE TIMI 58 study clearly demonstrated that Dapagliflozin was non inferior in reducing major adverse cardiovascular events (MACE) in patients with T2DM and high CV risk compared with placebo. 27% risk reduction in heart failure hospitalisation was noted along without increased risk of amputation. DAPA HF evaluated the efficacy and safety of the dapagliflozin in patients with HF and reduced ejection fraction, irrespective of the presence or absence of diabetes. Patients with symptomatic HF due to reduced ejection fraction treated with dapagliflozin had positive outcomes with reduction in cardiovascular deaths and HF events. The DAPA-CKD trial which was conducted to assess the efficacy and safety of dapagliflozin in patients with chronic kidney disease (CKD), with or without type 2 diabetes found that it significantly lowered the risk of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes in patients with CKD, regardless of the presence or absence of diabetes. Ongoing trials like DELIVER, DAPA ACT HF-TIMI 68, DICTATE-AHF, HF readmission study, DAPA MI Study, Effectiveness of Dapagliflozin for Weight Loss, will throw more light on the precise effects of dapagliflozin in several clinical scenarios. To conclude - Dapagliflozin was well studied not only in T2DM but also in HF and CKD patients with positive results and good safety profile.

Clinical Evidence of Evogliptin plus Metformin in Management of Type 2 Diabetes mellitus.

Achieving adequate glycemic control in type 2 diabetes mellitus (T2DM) remains a difficult but achievable goal. Oral agents (OADs) are important option for management of T2DM. Most T2DM patients require more than one medication for adequate glycemic control. Metformin based combination therapy is recommended when monotherapy is insufficient. Evogliptin is a recently developed dipeptidyl peptidase-4 (DPP-4) inhibitor, which can to be combined with metformin for treating T2DM. Combination therapy of Evogliptin and Metformin lowers blood glucose via augmentation of insulin secretion, suppression of glucagon secretion, and insulin sensitization. Co-administration of Evogliptin and Metformin showed no clinically relevant pharmacokinetic differences compared to the administration of each drug alone. Combination therapy of Evogliptin and Metformin also provides significantly better glycemic control compared to the respective monotherapies. Efficacy and safety of Evogliptin and Metformin had been demonstrated in several multicentre randomized clinical trials conducted in various countries like South Korea, Russia and India. Consequently, fixed dose combination (FDC) of Evogliptin and Metformin is approved in South Korea and India. Complexity of the treatment regimen and polypharmacy are well-known factors of poor medication adherence and FDCs have the potential to improve adherence by reducing the pill burden. Adoption of this combination therapy in clinical practice for management of T2DMs will provide a greater degree of HbA1c reduction than that observed with the use of either drug as monotherapy, and is unlikely to cause significant hypoglycemia. Combination therapy of Evogliptin and Metformin is a promising strategy in the treatment of T2DM.

Isoniazid induced convulsions at therapeutic dose in an alcoholic and smoker patient.

We report a case of isoniazid induced convulsions in 35 years old male alcoholic and smoker patient receiving intensive phase therapy for pulmonary tuberculosis. A case was confirmed by accidental positive de-challenge and rechallenge as well as ruled out other conditions. Use of isoniazid in alcoholic and smoker patient required a caution for prevention of neurological adverse reactions. Pyridoxine should always be prescribed to such patients for the prevention of such adverse reaction.