SGLT2i as a First-line Antihyperglycemic in the Management of Type 2 Diabetes in the Context of Indians: A Systematic Review and Consensus.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been used for almost a decade and have proven to be effective not only in managing Type 2 diabetes (T2D), but their cardio and renal protective features make them very useful in managing patients with risk of multiple comorbidities. This systematic review was undertaken by the authors because there is no evidence currently available in India that has studied the suitability of SGLT2i as a first-line agent in patients newly diagnosed with T2D in India. MATERIALS AND METHODS: First, literature was searched to identify features that are considered important when deciding on a first-line agent for managing T2D. A total of 5 broad topics were identified-glycemic control, extra glycemic effects, antihyperglycemic combination therapy, safety, and cost-effectiveness. These domains had further subheadings, and a total of 16 domains were identified. Metformin is the drug of choice as a first-line agent in such situations and has been considered the gold standard for evaluating the effects of SGLT2i across these domains. A systematic literature review on each domain was conducted to compare SGLT2i with the gold standard in Indian patients newly diagnosed with T2D. Evidence was graded (levels of evidence (LoE)-A, B, and C), and recommendations (class of recommendation (CoR)-I, II, and III) were classified by the expert group as defined in the methodology. RESULTS: According to the systematic reviews conducted, 11 domains had Level A evidence, 2 domains (impact on lipids and gut microbiome) had Level B, and 3 domains had Level C (ß-cell function, renal protection, and glycemic variability) evidence. Based on evidence and expert opinion, the authors recommend SGLT2i as a first-line agent for managing newly diagnosed patients with T2D with a Class I recommendation for 13 domains and Class II for the remaining 3 (impact on lipids, gut microbiome, and ß-cell function). Although a poorer level of evidence (Level C) was available for the glycemic variability domain, the authors still reported this as Class I recommendations according to their expert opinion and consensus. CONCLUSION: This article advocates adopting SGLT2 inhibitors as the primary treatment choice for treating patients with newly diagnosed T2D in India.

Maintenance of glycaemic control with liraglutide versus oral antidiabetic drugs as add-on therapies in patients with type 2 diabetes uncontrolled with metformin alone: A randomized clinical trial in primary care (LIRA-PRIME).

AIM: To compare (in the LIRA-PRIME [NCT02730377], a randomized open-label trial), the efficacy of liraglutide in controlling glycaemia versus an oral antidiabetic drug (OAD) in patients with uncontrolled type 2 diabetes (T2D), despite metformin use in a primary care setting (n = 219 sites, n = 9 countries). MATERIALS AND METHODS: Adults (n = 1991) with T2D (HbA1c 7.5%-9.0%) receiving metformin were randomized 1:1 to liraglutide (≤1.8 mg/d) or one OAD, selected by the investigator, added to metformin, for up to 104 weeks. Primary endpoint: time to inadequate glycaemic control (HbA1c > 7.0%) at two scheduled consecutive visits after week 26. Outcomes were assessed for liraglutide versus a pooled OAD group, and (post hoc) liraglutide versus sodium-glucose co-transporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulphonylureas individually. RESULTS: Among randomized patients (liraglutide, n = 996; OAD, n = 995), 47.6% were female, mean age was 57.4 years and mean HbA1c was 8.2%. Median time to inadequate glycaemic control was 44 weeks longer with liraglutide versus OAD (109 weeks [25% percentile, 38; 75% percentile, not available] vs. 65 weeks [25% percentile, 35; 75% percentile, 107], P < .0001). Changes in HbA1c and body weight at week 104 or at premature treatment discontinuation significantly favoured liraglutide over OAD. Hypoglycaemia rates were comparable between groups and few patients discontinued because of adverse events (liraglutide, 7.9% [n = 79]; OAD, 4.1% [n = 41]). Similar results were observed in the post hoc analysis for liraglutide versus individual OAD classes. CONCLUSIONS: Glycaemic control was better maintained with liraglutide versus OAD, supporting liraglutide use when intensifying therapy in primary care patients with T2D.

Trial design and baseline data for LIRA-PRIME: A randomized trial investigating the efficacy of liraglutide in controlling glycaemia in type 2 diabetes in a primary care setting.

AIMS: Using a pragmatic approach, the LIRA-PRIME trial aims to address a knowledge gap by comparing efficacy in controlling glycaemia with glucagon-like peptide-1 analog liraglutide vs oral antidiabetic drugs (OADs) in patients with type 2 diabetes (T2D) uncontrolled with metformin monotherapy in primary care practice. We report the study design and patient baseline characteristics. MATERIALS AND METHODS: This 104-week, two-arm, open-label, active-controlled trial is active in 219 primary care practices across nine countries. At screening, eligible patients with T2D were at least 18 years of age, had been using a stable daily dose of metformin ≥1500 mg or the maximum tolerated dose for ≥60 days, and had a glycated haemoglobin (HbA1c) of 7.5% to 9.0%, measured ≤90 days before screening. Patients were randomized (1:1) to liraglutide or OAD, both in addition to pre-trial metformin. Individual OADs were chosen by the treating physician based on local guidelines. The primary endpoint is time to inadequate glycaemic control, defined as HbA1c above 7.0% at two scheduled consecutive visits after the first 26 weeks of treatment. RESULTS: The trial randomized 1997 patients with a mean (standard deviation) age of 56.9 (10.8) years, T2D duration of 7.2 (5.9) years (range, <1-47 years), and HbA1c of 8.2%. One-fifth of patients had a history of diabetes complications, and most were overweight (24.8%) or had obesity (65.3%). CONCLUSIONS: This pragmatically designed, large-scale, multinational, randomized clinical trial will help guide treatment decisions for patients with T2D who are inadequately controlled with metformin monotherapy and treated in primary care.

Recommendations for Vaccination Against Seasonal Influenza in Adult High Risk Groups: South Asian Recommendations.

Influenza is a global public health problem and concern especially in high risk people. Prevention plays a key role in avoiding complications of influenza related illnesses. Despite the existing prevalence of influenza, and documented importance of vaccination, the uptake of influenza vaccine is very poor. This document provide recommendations for influenza vaccination in high-risk individuals and help implement best practices in the South Asian region and improve coverage of influenza vaccination to achieve better outcomes in this population.

Management of diabetic dyslipidemia in Indians: Expert consensus statement from the Lipid Association of India.

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians.

Insulin gene mutations linked to permanent neonatal diabetes mellitus in Indian population.

BACKGROUND AND AIM: Neonatal diabetes mellitus (NDM) is a rare monogenic disorder of pancreatic beta cell mass and/or function. In the present study we aimed to evaluate the INS gene mutations in a cohort of children with Permanent Neonatal Diabetes Mellitus (PNDM) and to explore the clinical and genetic characteristics of PNDM caused by INS mutations. METHODS: Direct sequencing of all exons of INS genes was carried out in 189 children with PNDM. Clinical and biochemical data were collected and correlated. The pathogenicity of mutations was determined based on the American College of Medical Genetics and Genomics and Association of Medical Pathology guidelines. RESULTS: Two novel mutations (His34Pro, Leu35Met) in a compound heterozygous state and seven known mutations (Gly32Ser, Phe48Cys, Arg89Cys, Cys96Tyr, Ser98Ile, Try108Asp and Cys109Phe) in the INS gene were identified in 8 patients out of the total of 189 PNDM children studied. Four mutations were involved in defects with disulphide bond formation and hence were in crucial regions of the gene. All the mutations were de novo in origin. CONCLUSIONS: This is the first comprehensive study from India to investigate the insulin gene mutations in PNDM and to show that INS gene mutations also contribute to the causation of PNDM.

Clinical practice guidelines 2019: Indian consensus-based recommendations on influenza vaccination in adults.

Influenza, a common cause of acute respiratory infections, is an important health problem worldwide, including in India. Influenza is associated with several complications; people with comorbidities and the elderly are at a higher risk for such complications. Moreover, the influenza virus constantly changes genetically, thereby worsening therapeutic outcomes. Vaccination is an effective measure for the prevention of influenza. Despite the availability of global guidelines on influenza vaccination in adults, country-specific guidelines based on regional variation in disease burden are required for better disease management in India. With this aim, the Indian Chest Society and National College of Chest Physicians of India jointly conducted an expert meeting in January 2019. The discussion was aimed at delineating evidence-based recommendations on adult influenza vaccination in India. The present article discusses expert recommendations on clinical practice guidelines to be followed in India for adult influenza vaccination, for better management of the disease burden.

Clinical practice guidelines 2019: Indian consensus-based recommendations on pneumococcal vaccination for adults.

Similar to the global scenario, pneumococcal diseases are a significant health concern in India. Pneumococcal diseases occur frequently among adults and are largely preventable through vaccines. Globally, several guidelines and recommendations are available for pneumococcal vaccination in adults. However, owing to wide variations in the disease burden, regulatory landscape, and health-care system in India, such global guidelines cannot be unconditionally implemented throughout the country. To address these gaps, the Indian Chest Society and National College of Chest Physicians of India jointly conducted an expert meeting in January 2019. The aim of the discussion was to lay down specific evidence-based recommendations on adult pneumococcal vaccination for the country, with a view to further ameliorate the disease burden in the country. This article presents an overview of the closed-door discussion by the expert members on clinical practice guidelines to be followed for adult pneumococcal vaccination in India.

Consensus recommendations on exploring effective solutions for the rising cost of diabetes.

Diabetes remains asymptomatic for a long period of time and its real burden gets noticed only once the complications set in. The number of individuals affected with the disease is also on the rise and more so in the low income countries. This scenario calls for urgent precautionary measures that need to be undertaken to equip ourselves to fight against this chronic disease. Individuals with financial constraints cannot afford to access even the basic treatment facilities and thus stands the most burdened. The International Diabetes Federation calls for 'Eyes on Diabetes' for the society to focus on early screening and early intervention. The rising cost of diabetes results from delayed and denied treatment. The panel discussion organized as a part of 4th Annual global diabetes convention of Jothydev's Professional Education Forum (JPEF, 2016) facilitated a platform to address diabetes as a serious health concern that needs to be given immediate priority by the policymakers as well as public and also to discuss about the feasible measures that will help achieve cost effective and affordable diabetes treatment. This was followed by in-depth literature search and finally a set of recommendations have been arrived at by the key opinion leaders to realize the dream of affordable diabetes care to all deserving individuals.