Gla-100 Development: a Story of 'Serendipitous' Disruptive Innovation.

Ever since the discovery of insulin a century ago, relentless attempts have been made to develop insulins that closely mimic the timeaction- profile of human physiologic insulin. The early basal insulins like neutral protamine Hagedorn (NPH), were intermediate-acting, with high risk of hypoglycemia. These primary limitations led to attempts at developing improved basal insulins with a longer duration of action. After several attempts at prolonging insulin action using phenol and structural modifications of the insulin hexamer, insulin glargine was developed in 1988. The superior and unique pharmacological properties, longer duration of action, and significantly lowered risk of hypoglycemia enabled insulin glargine to be distinguished from NPH as a better basal insulin, providing holistic glycemic control. The present review highlights the circumstances that led to the search of truly basal insulins, focusing on the journey of insulin glargine 100 U/mL (Gla-100).

Consensus on Insulin Dose and Titration Algorithms in Ambulatory Care of Type 2 Diabetes in India.

INSTRUCTION: Insulin is the oldest of the currently available treatment options in Type 2 diabetes mellitus (T2DM) and is considered as the most effective glucose lowering agent. Despite this, decision on starting insulin therapy is often delayed in India as well as worldwide due to various barriers at both patient and physician levels. Appropriate insulin dosing and titration is also critical to the successful achievement of tight glycaemic control. OBJECTIVE: To provide simple and easily implementable guidelines to primary care physicians on appropriate insulin dosing and titration of various insulin regimens for both initiation and intensification. METHODOLOGY: Each insulin regimen (once daily [OD] basal, OD, twice daily and thrice daily premixed, basal-plus and basal-bolus) was presented and evaluated for dosing and titration based on established guidelines, data from approved pack inserts, and published scientific literature. These evaluations were then factored into the national context based on the expert committee representatives patient-physician experience in their clinical practice and common therapeutic practices followed in India. RESULTS: Recommendations for dosing and titration of basal, basal-plus, premixed and basal-bolus insulins were developed. The key recommendations are that insulin doses can be adjusted once or twice weekly; adjustment can be based on lowest/mean of three recent self-monitoring of plasma glucose pre-meal/fasting plasma glucose (FPG) values. The titration should be based on FPG or pre-meal value of 80-130 mg/dL and the dose should be reduced by 10-20% for patients reporting hypoglycaemia(<70mg/dL). CONCLUSIONS: The consensus based recommendations mentioned in this paper will be a useful reference tool for health care practitioners, to initiate, optimise and intensify insulin therapy and to successfully achieve optimal glucose control.

Effectiveness of Dapagliflozin as Add-On to Metformin with or without Other Oral Antidiabetic Drugs in Type 2 Diabetes Mellitus: A Multicentre, Retrospective, Real-World Database Study.

BACKGROUND: Real-world Indian studies evaluating effectiveness of dapagliflozin as an add-on to other oral antidiabetic drugs (OAD) in patients with type 2 diabetes mellitus (DM) are scarce. METHODS: An electronic medical record (EMR)-based, retrospective, multicentre study was conducted to evaluate the effectiveness of dapagliflozin as add-on therapy in adult patients with inadequately controlled DM on metformin with or without other OAD. Baseline characteristics (visit 1: metformin or metformin plus OAD treatment for at least 30 days) and treatment-related outcomes (visit 2: follow-up) considered between 60 and 140 days after adding/switching dapagliflozin [glycated haemoglobin (HbA1c), body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP)] were analysed. RESULTS: A total of 3616 patients were screened from 478 centres. Most patients had received dapagliflozin (D) + metformin (M) + at least one other OAD [D + M + OAD, n = 2907 (80.4%), 408 followed-up with HbA1c reported], while 709 patients (19.6%, 138 followed-up with HbA1c reported) received dapagliflozin + metformin (D + M). Treatment with dapagliflozin as an add-on therapy resulted in significant change in HbA1c (-1.1 ± 1.44%; p < 0.05 for HbA1c subgroup ≥ 7.5%; -1.6 ± 1.41%; p < 0.05 for HbA1c subgroup ≥ 8%) at visit 2 compared with visit 1. Significant change in body weight (-1.4 ± 3.31 kg; p < 0.05 for HbA1c subgroup ≥ 7.5%; - 1.5 ± 3.22 kg; p < 0.05 for HbA1c subgroup ≥ 8%) was observed at visit 2. Similarly, a significant change in BMI was noted for the HbA1c subgroup ≥ 7.5% (-1.0 ± 8.38 kg/m2). However, the change in BMI in the HbA1c subgroup ≥ 8% was noted to be -1.4 ± 10.4 kg/m2, which was not statistically significant (p = 0.08). In the overall study population, significant change in the SBP (-4.5 ± 14.9 mmHg; p < 0.05 for HbA1c subgroup ≥ 7.5%; -4.5 ± 15.1 mmHg; p < 0.0001 for HbA1c subgroup ≥ 8%) was observed at visit 2 compared with visit 1. On identical lines, significant change in DBP (-1.5 ± 8.94 mmHg; p < 0.05 for HbA1c subgroup ≥ 7.5%; -1.4 ± 8.91 mmHg; p < 0.05 for HbA1c subgroup ≥ 8%) was noted. CONCLUSIONS: Dapagliflozin showed significant improvement in glycemic parameter, BMI and BP when added to metformin, with or without other OADs in a real-world scenario.

Rising cost of insulin: A deterrent to compliance in patients with diabetes mellitus.

BACKGROUND AND AIMS: The rapid increase in burden of type 2 diabetes mellitus (T2DM), poses a huge medico-economic challenge, especially when the cost of care is funded by out-of-pocket expenses. The aim of this review is to highlight various issues associated with rising cost of insulin, prevalence of cost-related insulin underuse, insulin related cost-saving behaviors, and viable solutions for the benefit of patients with T2DM receiving insulin. METHODS: Electronic databases (PubMed and Google Scholar) from 2000 to 2020 were searched using the key terms uncontrolled diabetes mellitus, insulin therapy, glycemic control, direct cost, indirect cost, out-of-pocket expenses, cost-related insulin underuse, cost-saving behaviors, and biosimilar insulin in developed countries and India. RESULTS: In majority of the patients with T2DM on monotherapy, addition of another oral antidiabetic agent is required. Despite these measures, the target glycemic goals are not achieved in majority of the patients resulting in various complications. These complications can be prevented and target glycemic goals can be achieved with early initiation of insulin therapy. However, rising cost is a major deterrent to the lifelong use of insulin. This results in non-compliance and further deterioration of glycemic control. Recently, biosimilar insulins have revolutionized the management of T2DM and look promising from the economic point of view. CONCLUSIONS: Biosimilar insulins are likely to further enhance the compliance of patients and should be used whenever feasible in patients with DM. However, the patient, along with prescriber should be allowed to make shared, informed decisions regarding the insulin they wish to use.

Insulinization in T2DM with Basal Analogues During COVID-19 Pandemic: Expert Opinion from an Indian Panel.

The ongoing global pandemic of the coronavirus disease 2019 (COVID-19) has placed a severe strain on the management of chronic conditions like diabetes. Optimal glycemic control is always important, but more so in the existing environment of COVID-19. In this context, timely insulinization to achieve optimal glycemic control assumes major significance. However, given the challenges associated with the pandemic like restrictions of movement and access to healthcare resources, a simple and easy way to initiate and optimize insulin therapy in people with uncontrolled diabetes is required. With this premise, a group of clinical experts comprising diabetologists and endocrinologists from India discussed the challenges and potential solutions for insulin initiation, titration, and optimization in type 2 diabetes mellitus (T2DM) during the COVID-19 pandemic and how basal insulin can be a good option in this situation owing to its unique set of advantages like lower risk of hypoglycemia, ease of training, need for less monitoring, better adherence, flexibility of using oral antidiabetic drugs, and improved quality of life compared to other insulin regimens. The panel agreed that the existing challenges should not be a reason to delay insulin initiation in people with uncontrolled T2DM and provided recommendations, which included potential solutions for initiating insulin in the absence or restriction of in-person consultations; the dose of insulin at initiation; the type of insulin preferred for simplified regimen and best practices for optimal titration to achieve glycemic targets during the pandemic. Practical and easily implementable tips for patients and involvement of stakeholders (caregivers and healthcare providers) to facilitate insulin acceptance were also outlined by the expert panel. Simplified and convenient insulin regimens like basal insulin analogues are advised during and following the pandemic in order to achieve glycemic control in people with uncontrolled T2DM.

Diagnosis and Management of Hypothyroidism: Addressing the Knowledge-Action Gaps.

Hypothyroidism presents a large epidemiological burden in India. As a result of subtle and nonspecific clinical symptoms and signs, the condition often goes undiagnosed and is not adequately treated when it is detected. There is heterogeneity in the diagnostic and treatment approaches to hypothyroidism. As a result of the physiological changes in thyroid hormones with age and illness, it is important to tailor the diagnosis and management of this condition in specific populations including pregnant women, infants, children, geriatric patients, and those with comorbid conditions. Enhanced understanding and education of physicians and patients can help to improve the outcomes of treatment in hypothyroidism which should be focused on patient-centered care. Policies and reforms should be crafted and implemented at the national level to curb public health challenges of hypothyroidism. This publication summarizes the recommendations of a national advisory board meeting to identify and bridge the gaps in understanding of the diagnosis and treatment of hypothyroidism in India. As a complement to clinical judgment, these recommendations will foster the diagnosis and management of hypothyroidism in the community and clinics for the benefit of the patients. FUNDING: Merck Ltd, India.

Patient-centered Management of Hypothyroidism.

This communication from the National Indian Patient-centered Thyroid management group (InPACT) deals with a novel, yet essential, aspect of hypothyroidism management. The authors describe the role and scope of patient-centered care in this condition. They focus on the relevance of a patient-centered clinical approach, which will help decide appropriate targets, as well as techniques to achieve those targets. Means of helping persons with hypothyroidism live a healthy life, such as education about precaution in concomitant food and medications intake, as well as sick day management, are discussed.

Medication Counseling for Thyroxine.

This communication from the National Indian Patient-centered Thyroid Management group provides a useful tool to help in medication counseling during hypothyroidism management. The authors classify and list aspects of thyroxine use which must be discussed with patients on thyroxine supplementation or replacement. Issues related to concomitant food and medications intake, preconception and pregnancy management, as well as sick day care, are also discussed.