Manash P Baruah

Glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes: Past, present, and future.

Glucagon-like peptide-1 (GLP-1)–based therapy improves glycaemic control through multiple mechanisms, with a low risk of hypoglycaemia and the additional benefit of clinically relevant weight loss. Since Starling and Bayliss first proposed the existence of intestinal secretions that stimulate the pancreas, tremendous progress has been made in the area of incretins. As a number of GLP-1 receptor agonists (GLP-1 RAs) continue to become available, physicians will soon face the challenge of selecting the right option customized to their patients needs. The following discussion, derived from an extensive literature search using the PubMed database, applying the terms incretin, GLP-1, exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide, semaglutide, and taspoglutide, provides a comprehensive review of existing and upcoming molecules in the GLP-1 RA class in terms of their structure, pharmacological profiles, efficacy, safety, and convenience. Search Methodology: A literature search was conducted using the PubMed database, applying the terms incretin, GLP-1, exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide, semaglutide, and taspoglutide. Relevant articles were those that discussed structural, pharmacokinetic and pharmacodynamic differences, classification, long-acting and short-acting GLP-1 RAs, phase 3 trials, and expert opinions. Additional targeted searches were conducted on diabetes treatment guidelines and reviews on safety, as well as the American Diabetes Association/European Society for Study of Diabetes (ADA/EASD) statement on pancreatic safety.

Updated guidelines on screening for gestational diabetes

Gestational diabetes mellitus (GDM) is associated with an increased risk of complications for both mother and baby during pregnancy as well as in the postpartum period. Screening and identifying these high-risk women is important to improve short- and long-term maternal and fetal outcomes. However, there is a lack of international uniformity in the approach to the screening and diagnosis of GDM. The main purpose of this review is to provide an update on screening for GDM and overt diabetes during pregnancy, and discuss the controversies in this field. We take on debatable issues such as adoption of the new International association of diabetes and pregnancy study groups criteria instead of the Carpenter and Coustan criteria, one-step versus two-step screening, universal screening versus high-risk screening before 24 weeks of gestation for overt diabetes, and, finally, the role of HbA1c as a screening test of GDM. This discussion is followed by a review of recommendations by professional bodies. Certain clinical situations, in which a pragmatic approach is needed, are highlighted to provide a comprehensive overview of the subject.

Endocrine Society of India management guidelines for patients with thyroid nodules: A position statement

Thyroid nodules are common. Thyroid cancer is rarer. No guidelines exist for management of thyroid nodules in the Indian context and these recommendations are intended for this purpose. The consensus committee reviewed important articles, including previously published consensus statements. Management points were scored according to the level of evidence. These guidelines cover the clinical evaluation and include the interpretation of imaging and fine needle aspiration cytology of thyroid nodules. The guidelines also cover the management of special situations like thyroid incidentalomas, cystic thyroid lesion and nodules detected during pregnancy. The consensus guidelines represent a summary of current medical evidence for thyroid nodule management and the committee has attempted to optimize the guidelines for the clinical practice setting in India.

Degludec insulin: A novel basal insulin

This paper reviews a novel insulin analogue, degludec, which has the potential to emerge as an ideal basal insulin. It reviews the limitations of existing basal insulin and analogues, and highlights the need for a newer molecule. The paper discusses the potential advantages of degludec, while reviewing its pharmacologic and clinical studies done so far. The paper assesses the potential role of insulin degludec and degludec plus in clinical diabetes practice.

National recommendations: Psychosocial management of diabetes in India

Although several evidence-based guidelines for managing diabetes are available, few, if any, focus on the psychosocial aspects of this challenging condition. It is increasingly evident that psychosocial treatment is integral to a holistic approach of managing diabetes; it forms the key to realizing appropriate biomedical outcomes. Dearth of attention is as much due to lack of awareness as due to lack of guidelines. This lacuna results in diversity among the standards of clinical practice, which, in India, is also due to the size and complexity of psychosocial care itself. This article aims to highlight evidence- and experience-based Indian guidelines for the psychosocial management of diabetes. A systemic literature was conducted for peer-reviewed studies and publications covering psychosocial aspects in diabetes. Recommendations are classified into three domains: General, psychological and social, and graded by the weight they should have in clinical practice and by the degree of support from the literature. Ninety-four recommendations of varying strength are made to help professionals identify the psychosocial interventions needed to support patients and their families and explore their role in devising support strategies. They also aid in developing core skills needed for effective diabetes management. These recommendations provide practical guidelines to fulfill unmet needs in diabetes management, and help achieve a qualitative improvement in the way physicians manage patients. The guidelines, while maintaining an India-specific character, have global relevance, which is bound to grow as the diabetes pandemic throws up new challenges.

Forum for Injection Technique (FIT), India: the Indian recommendations 2.0, for best practice in Insulin Injection Technique, 2015

As injectable therapies such as human insulin, insulin analogs, and glucagon-like peptide-1 receptor agonists are used to manage diabetes, correct injection technique is vital for the achievement of glycemic control. The forum for injection technique India acknowledged this need for the first time in India and worked to develop evidence-based recommendations on insulin injection technique, to assist healthcare practitioners in their clinical practice.

Degludec: A Novel Basal Insulin.

Limitations of conventional human basal insulins like NPH have led to the development of more stable and peak less analogs. However, the first generation of basal analogs like glargine and detemir has certain shortcomings which do not allow them to be termed ideal basal insulin. Degludec, a novel basal insulin analog has the potential to overcome these limitations. This paper reviews the potential advantages of degludec over existing basal insulins and analogs. It discusses the basic and clinical studies performed on degludec so far, and highlights the possible role this molecule can play in the management of diabetes mellitus. In this paper, the recent patents on basal insulin have been reviewed so as to provide an insight into the advances in this field. In this article, we present a review of Degludec, as well as related patents.

Forum for injection techniques, India: the first Indian recommendations for best practice in insulin injection technique.

Advances in the treatment of diabetes have led to an increase in the number of injectable therapies, such as human insulin, insulin analogues, and glucagon-like peptide-1 analogues. The efficacy of injection therapy in diabetes depends on correct injection technique, among many other factors. Good injection technique is vital in achieving glycemic control and thus preventing complications of diabetes. From the patients’ and health-care providers’ perspective, it is essential to have guidelines to understand injections and injection techniques. The abridged version of the First Indian Insulin Injection technique guidelines developed by the Forum for Injection Technique (FIT) India presented here acknowledge good insulin injection techniques and provide evidence-based recommendations to assist diabetes care providers in improving their clinical practice.

The novel use of GLP-1 analogue and insulin combination in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a global public health problem. Due to the progressive nature of the disease, a combination(s) of two or more drugs acting on different pathophysiological process is often necessary to achieve early and sustained achievement of individualized glycemic targets. At the same time, choosing the safest option to avoid hypoglycemia is of paramount importance. GLP-1 analogues are a relatively recent class of anti-diabetic drugs, and are highly effective with an acceptable safety profile. Attempts have been made to combine GLP-1 analogues with basal insulin for management of T2DM. Presently GLP-1 analogues like exenatide/long acting exenatide and liraglutide have been co-administered with basal insulin like glargine and detemir respectively, and are approved by regulatory agencies. Currently a fixed dose combination (FDC) of insulin degludec and liraglutide is under development. GLP-1 analogue and insulin as FDC or by co-administration, is a rational method of controlling fasting and postprandial glucose effectively. The efficacy and safety of this combination has been studied in a wide population with promising outcomes. Innovative use of GLP-1 analogues beyond diabetes is also being attempted, and a variety of patents are filed or granted for the same. This review summarizes the current status of GLP-1 and insulin combination in the management of T2DM and highlights the new frontiers in research involving GLP-1. Patents on combination of GLP-1 and insulin which were granted earlier, and the ones which have been applied for, are also discussed.

Liraglutide: A review of its therapeutic use as a once daily GLP-1 analog for the management of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a progressive disease associated with significant morbidity and mortality. Even though progress have been accomplished in the management of type 2 diabetes, current treatment preferences for patients with this disease still fall short to address disease progression. With the present therapy, glycaemic control remains suboptimal and are often associated with weight gain and hypoglycaemia. Glucagon like peptide-1 (GLP-1) is an incretin hormone secreted from the small intestine that lowers fasting and postprandial glucose through multiple mechanisms including glucose-dependent insulin secretion, reduction of glucagon secretion, delaying gastric emptying and increased satiety. Liraglutide, a human glucagon-like peptide 1 (GLP-1) analogue is a treatment for T2DM that is administered as a once-daily subcutaneous injection. The efficacy and tolerability of liraglutide at doses of 0.6, 1.2, and 1.8 mg for T2DM, in combination with, and compared with, other T2DM treatments were investigated in the Liraglutide Effect and Action in Diabetes (LEAD) Phase III clinical trial program. In the LEAD trial, treatment with liraglutide was associated with substantial improvements in glycaemic control and low risk of hypoglycaemia. In addition liraglutide significantly improved β-cell function, reduced systolic blood pressure (BP) and induced weight loss. Overall, liraglutide was well tolerated. Recent data on safety and efficacy of liraglutide from real-life clinical practice settings also reiterate the better therapeutic profile of this molecule. Based on results from the LEAD programme, and real-life clinical experience, liraglutide has been demonstrated as an effective therapeutic intervention even at the early stage of diabetes regardless of with what, it has been used.