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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.)

Background: Hypertension is the biggest contributor to global burden of disease and mortality. Increasing compliance with antihypertensive treatment and achieving a wide BP control in the population represents a major challenge for clinical practice. The benefits of single pill combination versus free-equivalent combination has been demonstrated in several meta-analyses and is now strongly supported by the latest 2018 ESC/ESH guidelines. The RAAS blocker with CCB and thiazide like diuretic is proposed as the optimal combination in patients inadequately controlled by two drugs., Objective: To assess the blood pressure control rate, safety, tolerability and quality of life with triple-drug SPC in patients with grade II/ III hypertension., Methods: Hypertensive patients uncontrolled (BP ≥ 140/90 mmHg) on two-drug therapy were recruited in an open-label, phase III clinical trial conducted in outpatient setting in India with 6 months treatment period. No other antihypertensive medication except the study medication was received by the patients., Results: Out of 218 evaluable patients the observed average blood pressure reduction achieved from baseline to end of study at 6 months was Systolic Blood Pressure (SBP) 28.5 mm Hg / Diastolic Blood Pressure (DBP) 13.8 mm Hg. The quality of life (QoL) questionnaire demonstrated improvement in QoL for all patients., Conclusion: This study showed the clinical efficacy, safety and acceptability of the perindopril/indapamide/amlodipine SPC in patients with grade 2/3 hypertension inadequately controlled with two-drug therapy. The clinical effectiveness was observed in more than 96 % patients. The benefit of single-pill combination (SPC) therapy in hypertension control was reconfirmed in this study., (© Journal of the Association of Physicians of India 2011.)

Objectives: A high level of parathyroid hormone (PTH) was recently identified as a risk factor for falling. As balance instability is one of the major risk factors for falls, we aimed to investigate whether high PTH concentrations are associated with poor balance in older persons., Study Design: Cross-sectional study with 127 community-dwelling older adults (75% female), aged 65-96 years, at the Falls and Fracture Clinic, Western Health-Sunshine Hospital, Melbourne, Australia. Patients with clinical conditions that could affect balance (e.g. Meniere's disease), denosumab users, and those with advanced kidney failure were excluded., Main Outcome Measures: We assessed dynamic balance by timed "up and go" (TUG)and four-square step tests, and by gait parameters; and static balance by posturography on a force platform. Blood tests provided values of PTH, vitamin D, calcium, albumin, and creatinine. Standard questionnaires were applied to assess clinical condition, medications and nutritional status, and to screen for depression., Results: For dynamic balance, elevated PTH concentrations resulted in increased time to complete the TUG test (β = 0.13; 95%CI: 0.01-0.26), indicating worse performance. For static balance, increased PTH was associated with increased instability in the center of pressure while standing with eyes closed on a hard surface (β = 0.38; 95%CI: 0.03-0.73). Both models were controlled for vitamin D, renal function, nutritional and depressive status, age, sex, and number of medications., Conclusion: Increasing concentrations of PTH in this population of older persons had an independent negative association with both static and dynamic balance, which could place them at risk of falls. However, longitudinal studies are still required., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: To assess the effects on glycaemic control of lixisenatide vs placebo as add-on treatment to basal insulin (BI) ± metformin and effects on glycated haemoglobin (HbA1c) reduction in patients with insufficiently controlled type 2 diabetes (T2D)., Methods: Patients (n = 448) with inadequately controlled T2D were randomized (1:1) to lixisenatide or placebo as add-on to BI ± metformin for 24 weeks after an 8-week run-in phase, during which BI was titrated to a target self-monitored plasma glucose (SMPG; 4.4-5.6 mmol/L). The primary endpoint was absolute change in HbA1c from baseline to week 24. Secondary efficacy endpoints included: percentage of responders; changes in 2-hour postprandial plasma glucose (PPG); 7-point SMPG (daily average); body weight (BW); total daily BI dose; fasting plasma glucose; and safety assessments., Results: Baseline demographics were similar in the two treatment groups. After insulin optimization during run-in, lixisenatide was superior to placebo in mean change from baseline (7.9% [standard deviation {s.d.}, 0.66] and 7.9% [0.70], respectively) to week 24 in HbA1c (least squares mean [standard error {s.e.}] change -0.62% [0.09] vs -0.11% [0.09]; P < .0001, respectively) and higher proportions of patients achieved HbA1c targets. Two-hour PPG, daily mean SMPG and mean BW were reduced further and daily BI dose was lower with lixisenatide than placebo (-1.12 kg vs 0.04 kg [P < .0001]; -3.0 U vs -1.9 U [P = .0033], respectively). Treatment-emergent adverse events were greater with lixisenatide than placebo (63.8% vs 40.8%, respectively). The incidence of symptomatic hypoglycaemia was similar (lixisenatide 15.6% vs placebo 13.5%)., Conclusions: In Asian patients insufficiently controlled on BI ± metformin, lixisenatide was superior to placebo in glycaemic control, with a tolerability profile in line with other glucagon-like peptide-1 receptor agonists., Clinical Trial Number: NCT01632163 (clinicaltrials.gov)., (© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents., Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Bangalore, India., Results: A total of 1533 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 1262), insulin detemir (n = 165), insulin aspart (n = 86), basal insulin plus insulin aspart (n = 11) and other insulin combinations (n = 2). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 9.2%) and insulin users (mean HbA1c: 8.8%) groups. After 24 weeks of treatment, both groups showed improvement in HbA1c (insulin naïve: -1.3%, insulin users: -1.5%). SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients., Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Objective: To review the results of primary in situ extracorporeal shock wave lithotripsy (ESWL) for the treatment of ureteric stones using a third-generation lithotripter, the Dornier MFL 5000 (Dornier Medizentechnic, Germany)., Patients and Methods: The study comprised a retrospective review of treatment outcome in 180 patients with 196 stones who were treated with primary in situ ESWL, assessing the success of this approach and establishing reasons for failure., Results: At the 3-month follow-up, 88% of patients were stone-free; 21 patients failed ESWL and were treated by ureteroscopic stone extraction with no complications. Stone-free rates were 90% for upper ureteric, 89% for middle-third and 86% for lower-third calculi. Twenty-one patients required auxiliary procedures in the form of JJ stenting or nephrostomy. Failure of ESWL was associated with stone size (>1.3 cm) but not location or inadequate treatment., Conclusion: Where prompt access to ESWL is available, primary in situ ESWL remains an effective form of treatment for all ureteric calculi, although stone-free rates are lower for larger stones.

Placentas, mothers, and neonates belonging to different socioeconomic groups were examined for morphometric and gross morphologic changes to assess the effect of maternal undernutrition. The mean maternal caloric intakes for socioeconomic Groups I, II, and IIII + IV are 2,919, 2420, and 1,589 calories per day, respectively, and differences were significant (P less than 0.001). The mean protein intakes were respectively, 76.1, 67.3, and 52.0 Gm. per day for socioeconomic Groups I, II, and III + IV, respectively (p less than 0.001). The birth weight, placental weight, volume, surface area, and number of cotyledon showed significantly decreasing trends (P less then 0.001) with the fall in socioeconomic group and maternal dietary intakes. Placentas of socioeconomic Group I had significantly higher incidence of well-defined cotyledons and central cord attachment. In lower socioeconomic groups and small-for-dates placentas there was significantly higher incidence of hemorrhages. There were no changes in incidences of placental infarcts, calcifications, and degeneration in various socioeconomic groups.