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Introduction: A slower adoption rate of fixed dose combinations (FDC) in diabetes management is partly due to insufficient data. This study evaluates the safety and efficacy of an FDC of dapagliflozin + sitagliptin + metformin hydrochloride extended release (XR), compared to a dual FDC of sitagliptin + metformin hydrochloride XR among patients with type 2 diabetes mellitus (T2DM) with poor glycemic control when treated with metformin monotherapy., Methods: A total of 274 patients with T2DM were randomized (1:1) to either arm X, receiving FDC of dapagliflozin (10 mg) + sitagliptin (100 mg) + metformin hydrochloride XR (1000 mg) (Dapa + Sita + Met) tablets, or arm Y, receiving sitagliptin phosphate (100 mg) + metformin hydrochloride XR (1000 mg) (Sita + Met) tablets, and treated for 16 weeks. The outcome measures included changes in hemoglobin A1c (HbA1c)(%), fasting plasma glucose (FPG), 2-h post-prandial glucose (PPG), weight, and the proportion of patients achieving target HbA1c levels of < 7.0% by week 16 of the study period., Results: The reduction in HbA1c at week 16 was significantly higher in arm X than in arm Y [estimated treatment difference (ETD), - 0.65% (95% CI - 0.76 to - 0.53; P < 0.0001)]. Arm X showed a marked decrease in FPG [ETD - 15.42 mg/dl; 95% CI (17.63, 13.22; P < 0.0001)], PPG [ETD - 30.39 mg/dl; 95% CI (35.59, 25.19; P < 0.0001)], and weight [ETD - 1.47 kg; 95% CI (1.59, 1.28; P < 0.0001)] after 16 weeks. In arm X, 54% of patients reached HbA1c < 7.0% compared to 29.9% in arm Y. The incidence of adverse events was comparable [13.14% (arm X) vs 12.4% (arm Y)]. There was no severe hypoglycemia-led treatment discontinuation., Conclusion: Among patients with T2DM who have poor glycemic control with metformin monotherapy, triple FDC (Dapa + Sita + Met) effectively helped achieve better glycemic response compared to dual FDC (Sita + Met), with a comparable safety and tolerability profile., Trial Registration: CTRI/2022/01/039857., Competing Interests: Declarations. Conflict of Interest: Dr Aushili Mahule, Dr Ashish Prasad, Dr Abhijit Pednekar & Dr Anthuvan Thamburaj are the employees of USV Private Limited. Awadhesh Kumar Singh, Ashok Kumar Das, L Sreenivas Murthy, Samit Ghosal, Rakesh Sahay, KVS Hari Kumar, Ganesh Hosahithlu Keshava, Mayur Agarwal, G Vijayakumar, Pramila Kalra, Piyush Lodha, Sambit Das, Shehla Shaikh, Soumik Goswami, T.P Ajish, Prashant Kumthekar, Mihir Upadhyay have no nothing to disclose. The sponsors of the project were the manufacturers of the marketed product of drugs used in this study. Ethical Approval: The study was conducted, monitored, evaluated, and audited to comply with the International Conference on Harmonization Good Clinical Practice guidelines. The study was conducted in accordance with the ethical guidelines for biomedical research on human patients by the Indian Council of Medical Research, ethical principles of the Declaration of Helsinki, and New Drugs and Clinical Trials Rules 2019. The study also received the institutional ethics committee approval at each of the 12 study sites (Supplementary material; Table S1). The master ethics approval was obtained from Institutional Ethics Committee, Maharaja Agrasen Superspecialty Hospital (IEC/APV/JAN/2022/07). Informed written consent was obtained from all the study participants., (© 2024. The Author(s).)

In India and the Southeast Asian population, hypertension and type 2 diabetes mellitus (T2DM) are the leading lifestyle-related diseases, responsible for a majority burden of morbidity and mortality. Multiple population-spanning studies have revealed the staggering prevalence of both diseases in India, and the prevalence of both will only increase further due to factors such as an aging population, rapid urbanization, increased obesity, and sedentary lifestyles. More than 50 percent of hypertensive patients in India are also diagnosed with T2DM, and a detailed management protocol for the same is required, especially when a major portion of the disease is managed at the primary care level. The Association of Physicians of India (API) guidelines for the management of hypertension in patients with T2DM have been formulated based on consultation with leading physicians, cardiologists, diabetologists, and endocrinologists of India and Southeast Asia, keeping in mind the challenges faced by the patients in these countries and the appropriate management protocols that will be beneficial. While standard office-based blood pressure (BP) measurement forms the cornerstone of hypertension diagnosis and demands a uniform methodology to be followed, home blood pressure monitoring (HBPM) is recommended for long-term follow-up with validated devices. Ambulatory blood pressure monitoring (ABPM) offers comprehensive insights crucial for cardiovascular (CV) risk stratification. The complications of diabetic hypertension can span from increased CV risk, heart failure (HF), and renal dysfunction, and nonpharmacological and pharmacological management should be aimed toward not only control of the BP values but also protecting the end organs. While nonpharmacological measures include a focus on nutrition and diet, they also focus on approaches to weight loss, including a novel section covering the benefits of yoga. The guideline also focuses on a novel section of factors influencing CV risk, especially in the Indian population. For the pharmacological management, the guidelines address each of the categories of antihypertensive drugs, emphasizing the significance of combination therapies in the management of diabetic hypertension. In line with leading global guidelines for the management of hypertension in T2DM, for diabetic patients who often struggle with BP management and carry a high CV risk, the recommended dual combination antihypertensive therapy is particularly crucial and should be considered as first-line management therapy. While angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) play a highly beneficial role in the management of diabetic hypertension, a combination of ACEi or ARB with dihydropyridine calcium channel blockers (DHP-CCBs) is recommended to reduce the risk of complications and enhance patient adherence. To achieve the target of effective BP control and end-organ protection, it is beneficial and recommended to include newer CCBs (e.g., cilnidipine) in the management protocol in combination with ACEi/ARBs. Combination therapy including ARBs and DHP-CCBs should be preferred over β-blockers and thiazides. Among the CCBs, cilnidipine, a novel molecule, is a more effective and safer option for diabetic hypertensive patients in India. β-blockers should be used if there is a history of myocardial infarction (MI), HF, coronary artery disease (CAD), or stable angina along with the initial hypertensive regimen. The guideline also focuses on the novel reno- and cardioprotective molecules such as finerenone and sodium-glucose cotransporter 2 inhibitors (SGLT2i) and their benefits in the management of diabetic hypertension., (© Journal of the Association of Physicians of India 2024.)

Micronutrients play a key role in human health, being involved in energy metabolism, immunity, cellular functioning, growth, and development. Deficiencies in micronutrients occur in individuals of all ages due to several factors, including inadequate diets, disease states, and overweight/obesity. Guidelines from the Indian Council of Medical Research (ICMR) National Institute of Nutrition (NIN) Expert Group on Nutrient Requirements for Indians (2023) have specified the Recommended Dietary Allowances (RDA) for macronutrients and micronutrients. In addition, a healthy diet is crucial for overall health and should be the first step toward addressing micronutrient deficiencies. When diet is inadequate, micronutrient supplements can be provided to compensate. An expert panel of Indian doctors was convened to develop a pathway toward micronutrient supplementation among the Indian population. This Consensus Statement recognizes that different populations have varying needs for specific micronutrients, and ensuring adequate intake of such micronutrients can improve health outcomes. The panel provided recommendations for dietary practices and micronutrient supplementation when diet is inadequate. Addressing micronutrient deficiencies at the primary care level can prevent chronic deficiencies and their consequences. This Consensus Statement can serve as a primer for physicians to monitor and address deficiencies and thus help individuals maintain their health., (© Journal of the Association of Physicians of India 2024.)

Introduction: This study compared efficacy and safety of triple drug fixed-dose combination (FDC) of dapagliflozin (DAPA) + sitagliptin (SITA) + metformin (MET) extended release (ER) with SITA + MET sustained release (SR) and DAPA + MET ER in patients with type 2 diabetes poorly controlled with metformin., Methods: This phase 3, randomized, open-label, active-controlled study included adult patients with glycated hemoglobin (HbA1c) ≥ 8% (64 mmol/mol) and ≤ 11% (97 mmol/mol), randomized in 1:1:1 ratio to receive either FDC of DAPA + SITA + MET ER (10 mg + 100 mg + 1000 mg) tablets once daily (n = 137) or co-administration of SITA + MET SR (100 mg + 1000 mg) tablets once daily (n = 139) or FDC of DAPA + MET ER (10 mg + 1000 mg) tablets once daily (n = 139). Primary endpoint was mean change in HbA1c from baseline to week 16., Results: Mean baseline HbA1c was approximately 9% (75 mmol/mol) in each treatment group. At week 16, adjusted mean reduction in HbA1c from baseline was significantly greater with DAPA + SITA + MET ER (- 1.73% [- 19.0 mmol/mol]) compared to SITA + MET SR (- 1.28% [- 14.1 mmol/mol]; difference of - 0.46% [- 5.1 mmol/mol], p < 0.001) and DAPA + MET ER (- 1.33% [- 14.6 mmol/mol]; difference - 0.4% [4.4 mmol/mol], p < 0.001). Similarly, at week 12, reduction in HbA1c from baseline was significantly greater with DAPA + SITA + MET ER compared to SITA + MET SR (p = 0.0006) and DAPA + MET ER (p = 0.0276). At week 16, DAPA + SITA + MET ER showed significant reduction in postprandial blood glucose compared to DAPA + MET ER (p = 0.0394) and significant reduction in fasting blood glucose with DAPA + SITA + MET ER compared to SITA + MET SR (p = 0.0226). The proportion of patients achieving HbA1c < 7.0% (53 mmol/mol) at week 16 was significantly higher with DAPA + SITA + MET ER (38.5%) versus SITA + MET SR (12.8%) (p < 0.001) and DAPA + MET ER (21.3%) (p = 0.0023). All study medications were well tolerated., Conclusion: Triple FDC of DAPA + SITA + MET ER tablets once daily was significantly better in achieving glycemic control versus dual combination once daily in patients with type 2 diabetes poorly controlled with metformin without any significant safety concerns., Trial Registration: CTRI/2021/11/038176, registered on 22 November 2021., (© 2023. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Objective: This post-authorization safety study (PASS) was conducted to evaluate the long-term safety and effectiveness of insulin degludec in patients with diabetes mellitus (DM) requiring insulin therapy in routine clinical practice in India., Methods: Data on glycated hemoglobin (HbA1c) and adverse events (AEs) were collected up to 12 months after insulin degludec initiation., Results: A total of 1057 adult patients with DM were enrolled, including 60.07% males with the mean duration of 22.2 ± 21.90 years with type 1 DM and 10.1 ± 7.37 years with type 2 DM and the mean HbA1c of 9.6 ± 1.9%. Insulin degludec was prescribed to improve HbA1c and fasting plasma glucose (FPG). Insulin degludec daily dose was increased from 14.8 ± 8.0 U to 18.0 ± 9.46 U over 12 months resulting in a significant decrease of HbA1c by 1.8 ± 1.68% compared with baseline. There were 84 events of confirmed hypoglycemia in 51 patients during the 12-month follow-up period, and 44 AEs were reported in 2.6% of patients, of which 2 AEs were serious and unrelated to the drug., Conclusion: Insulin degludec is well tolerated in patients with DM. It improves glycemic control with reduced HbA1c, FPG, and postprandial glucose, with a low risk of hypoglycemia., Competing Interests: There was no conflict of interest., (© 2022 Published by Elsevier Inc.)

Introduction/objectives: High serum concentrations of parathyroid hormone (PTH) have been associated with osteoporosis, sarcopenia and osteosarcopenia. Gait velocity is a predictor of adverse outcomes. This systematic review aimed to assess the observational evidence studying the association of PTH concentrations with gait velocity in adults., Methods: We searched PubMed, Embase (Ovid interface) and Cochrane (CENTRAL) for published studies evaluating circulating PTH in human adults aged >20 years, without date or language restriction. We excluded studies with patients on dialysis and if PTH was measured following any intervention having a potential effect on its concentrations. Primary outcome was gait velocity, defined as the time needed to walk a predetermined distance or distance walked during a fixed period at usual pace or fast pace. Two independent researchers conducted data extraction and evaluated the risk of bias. A third reviewer resolved disagreements. Risk of bias assessment was done using the National Heart, Lung and Blood Institute quality assessment tool., Results: A total of 681 articles were retrieved from the systematic search. Following full-text review and risk of bias assessment, 8 studies were included for final analysis. Of the included studies, three demonstrated a significant inverse association between high PTH concentrations and gait velocity, one study showed an indirect association, and two studies showed a non-significant association of increasing PTH levels with declining gait speed. Two studies showed no relation. In addition, three of the studies also highlighted a negative correlation between PTH levels and muscle strength., Conclusion: Our review of published studies suggests that higher concentrations of PTH are associated with reduced gait velocity in adults. This relationship deserves further exploration with RCTs designed to assess the effects of correcting abnormal circulating PTH levels on physical performance in adults., (Copyright © 2021 Elsevier B.V. All rights reserved.)